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SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized.,Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis.,We aim to systematically and comprehensively evaluate the association between thrombin generation parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 patients.,A total of 127 hospitalized patients with confirmed COVID-19, 24 hospitalized patients with SARS-CoV-2-negative pneumonia and 12 healthy subjects were included.,Clinical characteristics, thrombin generation triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed.,Despite the frequent use of heparin, COVID-19 patients had similar thrombin generation to healthy controls.,In COVID-19 patients, the thrombin generation lag-time positively correlated with markers of cell lysis (LDH), inflammation (CRP, IL-6) and coagulation (D-dimer), while the endogenous thrombin potential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with fibrinogen levels.,Patients with more prolonged lag-time and decreased ETP had higher peak ISTH-DIC scores, and had more severe disease (vascular events and death).,The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p = 0.006), and with the occurrence of major adverse events (composite end-point of vascular events and death) (HR 2.38; p = 0.004).,The thrombin generation ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19. | EV-TF activity is dramatically increased in patients with severe COVID-19 and is associated with an increased thrombotic risk.Compared with patients with septic shock, those with severe COVID-19 display a distinct EV profile with higher procoagulant activity.,EV-TF activity is dramatically increased in patients with severe COVID-19 and is associated with an increased thrombotic risk.,Compared with patients with septic shock, those with severe COVID-19 display a distinct EV profile with higher procoagulant activity.,Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century.,Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis.,Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events.,Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218).,The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P < .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters.,High EV-TF values were associated with an increased thrombotic risk in multivariable models.,Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1).,Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease. | 1 |
Acute stroke remains a medical emergency even during the COVID-19 pandemic.,Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations.,Here we present a series of four patients with COVID-19 that presented with acute stroke.,We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection.,All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study.,Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study.,Retrospective patient data were obtained from electronic medical records.,Informed consent was obtained.,We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection.,We elucidate the clinical characteristics, imaging findings, and the clinical course.,Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke.,Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should don appropriate personal protective equipment in every suspected patient.,Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
We report the case of a previously healthy 16‐year‐old male who developed myopericarditis following the second dose of his Pfizer‐BioNTech COVID‐19 vaccine, with no other identified triggers.,Adolescents and young adults experiencing chest pain after COVD‐19 vaccination should seek emergent medical care, and emergency providers should have a low threshold to consider and evaluate for myopericarditis.,More data are needed to better understand the potential association between COVID‐19 vaccines and myopericarditis.,If a true causal link is identified, the risk must also be viewed in context with the millions of patients who have been safely vaccinated and the known morbidity and mortality from COVID‐19 infection.,As we see widespread vaccine rollout, it is important that all potential adverse reactions are reported as we continue to monitor for more rare but potentially serious side effects not identified in vaccination trials. | There have been reports of myocarditis following COVID-19 vaccination.,We surveyed all hospitalized military personnel in the Isareli Defense Forces during the period of the COVID-19 vaccination operation (12/28/2021-3/7/2021) for diagnosed myocarditis.,We identified 7 cases of myocarditis with symptoms starting in the first week after the second dose of COVID-19 Pfizer-BioNTech vaccine.,One case of myocarditis diagnosed 10 days after the second dose of the vaccine was not included.,These 8 cases comprise of all events of myocarditis diagnosed in military personnel during this time period.,All patients were young and generally healthy.,All had mild disease with no sequalae.,The incidence of myocarditis in the week following a second dose of the vaccine was 5.07/100,000 people vaccinated.,Due to the nature of this report no causality could be established.,Clinicians should be aware of the possibility of myocarditis following Pfizer-BioNTech vaccination.,True incidence rates should be further investigated. | 1 |
Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
The SARS‐CoV‐2 virus binds to the angiotensin‐converting enzyme 2 (ACE2) receptor for cell entry.,It has been suggested that angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID‐19 infection.,We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID‐19 at two hospitals with a multi‐ethnic catchment population in London (UK).,The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity.,Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset.,A total of 399 patients (33.3%) were taking ACEi or ARB.,Patients on ACEi/ARB were significantly older and had more comorbidities.,The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).,There was no evidence for increased severity of COVID‐19 in hospitalised patients on chronic treatment with ACEi or ARB.,A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials. | Acute infections are known cardiovascular disease (CVD) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections.,We hypothesized that in‐ and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections.,Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study).,Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in‐ and outpatient settings.,A case‐crossover design and conditional logistic regression were used to compare in‐ and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously.,A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed.,Inpatient infections (14‐day odds ratio [OR]=12.83 [5.74, 28.68], 30‐day OR=8.39 [4.92, 14.31], 42‐day OR=6.24 [4.02, 9.67], and 90‐day OR=4.48 [3.18, 6.33]) and outpatient infections (14‐day OR=3.29 [2.50, 4.32], 30‐day OR=2.69 [2.14, 3.37], 42‐day OR=2.45 [1.97, 3.05], and 90‐day OR=1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods (P<0.05).,Inpatient infection was also a stronger stroke trigger with the difference borderline statistically significant (P<0.10) for the 42‐ and 90‐day time periods.,In‐ and outpatient infections are associated with CVD risk.,Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis.,See Editorial by https://doi.org/10.1161/JAHA.118.011175 | 1 |
Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19).,We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population.,Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020.,COVID‐19 cases were defined based on hospitalization/death for COVID‐19.,Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases.,We performed consistency analysis to quantify the impact of potential unmeasured confounding.,Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19.,After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96).,MRA use was not associated with risk of any outcome.,Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.,In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19. | Concerns have been raised about the possible harmfulness of angiotensin-converter enzyme inhibitors (ACEi) and aldosterone receptor blockers (ARB) in patients with COVID-19.,However, few data from a European population have been published, especially from hypertensive patients.,To study the association between ACEi or ARB treatments and major adverse outcomes during hospitalisation in COVID-19 patients.,We studied 545 consecutive hypertensive patients admitted to our institution due to COVID-19 with respiratory involvement.,We analysed the incidence of combined event (death or mechanical ventilatory support) during hospitalisation, as well as the time to independent events.,188 (34.5%) patients presented the combined endpoint.,182 (33.4%) patients died, and 21 (3.9%) needed mechanical ventilatory support.,Patients with previous treatment with ACEi or ARB presented similar incidence of the combined endpoint during hospitalisation (31.6% vs.,41.8%; p = 0.08), with a lower all-cause mortality rate (30.4% vs.,41.2%; p = 0.03) compared with those without prior treatment.,Use of ACEi or ARB was not independently associated with lower incidence of the combined endpoint [Adjusted OR 0.675 (95% CI 0.298-1.528; p = 0.146)], but it was associated with lower mortality [Adjusted OR 0.550 (95% CI 0.304-0.930; p = 0.047)].,The use of ACEi or ARB was associated with less incidence of all-cause death during hospitalisation among hypertensive patients admitted with COVID-19 respiratory infection.,The online version of this article (10.1007/s40292-020-00409-7) contains supplementary material, which is available to authorized users. | 1 |
A 50-year-old man with no medical history of note presented with new onset of confusion and dyspnoea.,He tested positive for coronavirus (COVID-19), and subsequently, was admitted to the intensive care unit due to severe sepsis and acute renal failure requiring haemodialysis.,Shortly afterwards, he was intubated due to haemodynamic instability.,His blood culture was positive for Staphylococcus aureus bacteraemia, and echocardiogram showed evidence of vegetation in the aortic valve area.,He was commenced on intravenous antibiotics for infective endocarditis (IE).,Following extubation, he underwent an MRI of the spine due to increasing back pain.,This was suggestive of L5-S1 discitis, likely secondary to septic emboli from IE.,A few days later, he developed acute ischaemia of the left toes and extensive thrombosis of the right cubital and left iliac veins.,Following a prolonged hospital admission, he was discharged home and later underwent an elective forefoot amputation from which he made a good recovery. | Patient: Male, 53-year-old,Final Diagnosis: Infective endocarditis,Symptoms: Dynpnea • fever,Medication:-,Clinical Procedure: Surgical aortic valve replacement,Specialty: Cardiac surgery,Challenging differential diagnosis,The worldwide spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) has created unprecedented situations for healthcare professionals and healthcare systems.,Although infection with this virus is considered the main health problem currently, other diseases are still prevalent.,This report describes a 59-year-old man who presented with symptoms of dyspnea and fever that were attributed to Covid-19 infection.,His clinical condition deteriorated and further examinations revealed a subjacent severe aortic regurgitation due to acute infective endocarditis.,Surgical treatment was successful.,The results of diagnostic tests for Covid-19 should be re-evaluated whenever there are clinical mismatches or doubts, as false-positive Covid-19 test results can occur.,Clinical interpretation should not be determined exclusively by the Covid-19 pandemic.,This case report highlights the importance of using validated and approved serological and molecular testing to detect infection with SARS-CoV-2, and to repeat tests when there is doubt about presenting symptoms. | 1 |
Some patients with severe COVID-19 develop prothrombotic autoantibodies that are similar to antiphospholipid antibodies found in autoimmune diseases.,Patients with severe COVID-19 are at high risk for occlusion of blood vessels of all sizes.,This prothrombotic phenotype is reminiscent of patients with lupus and antiphospholipid syndrome, who have long-lived circulating antiphospholipid autoantibodies.,In new work, Zuo et al. measured eight types of antiphospholipid antibodies in serum from patients hospitalized with COVID-19 and found at least one antibody in half of patients.,Antibody levels were associated with neutrophil and coagulation pathway activation.,Purified antibodies from some patients activated neutrophils in vitro and potentiated thrombosis when injected into mice.,Together, these findings suggest that autoantibodies are a potential therapeutic target in severe COVID-19.,Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions.,Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease.,Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies).,Case series have recently detected aPL antibodies in patients with COVID-19.,Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19.,These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM.,We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples.,Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units).,Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate.,Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals.,Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models.,These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic. | Supplemental Digital Content is available in the text.,Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood.,In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19.,A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls).,We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well.,We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis.,We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin.,Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity.,Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non-COVID-19 pneumonia.,Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability.,Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19.,Further work is necessary to determine the role of immunothrombosis in COVID-19. | 1 |
The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component.,While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study.,A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients.,The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities.,Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%).,At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases.,Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting.,In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19. | There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications. | 1 |
Acute myocardial infarction causes lethal injury to cardiomyocytes during both ischaemia and reperfusion (IR).,It is important to define the precise mechanisms by which they die in order to develop strategies to protect the heart from IR injury.,Necrosis is known to play a major role in myocardial IR injury.,There is also evidence for significant myocardial death by other pathways such as apoptosis, although this has been challenged.,Mitochondria play a central role in both of these pathways of cell death, as either a causal mechanism is the case of mitochondrial permeability transition leading to necrosis, or as part of the signalling pathway in mitochondrial cytochrome c release and apoptosis.,Autophagy may impact this process by removing dysfunctional proteins or even entire mitochondria through a process called mitophagy.,More recently, roles for other programmed mechanisms of cell death such as necroptosis and pyroptosis have been described, and inhibitors of these pathways have been shown to be cardioprotective.,In this review, we discuss both mitochondrial and mitochondrial‐independent pathways of the major modes of cell death, their role in IR injury and their potential to be targeted as part of a cardioprotective strategy.,This article is part of a special Issue entitled ‘Mitochondria as targets of acute cardioprotection’ and emerged as part of the discussions of the European Union (EU)‐CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225. | Research on cardioprotection has attracted considerable attention during the past 30 years following the discovery of ischemic preconditioning with great advances being made in the field, particularly in the description of the molecular signalling behind this cardioprotective intervention.,In a time when basic research is struggling to translate its findings into therapies in the clinical setting, this viewpoint has the intention of presenting to clinical and basic scientists how the reperfusion injury salvage kinase pathway has been described and dissected, as well as highlighting its relevance in cardioprotection. | 1 |
Established primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear.,We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events.,We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment.,We extracted relative risks (RR) and 95 % confidence intervals [CI] and visualised the number of reports with inverse (RR [CI]<1.00), or direct (RR [CI]>1.00) associations.,For hypertension (13/17 reports) and obesity (19/19 reports), there were direct associations with incident AF, as there are for coronary heart disease (CHD).,There were inverse associations for non-White ethnicity (5/5 reports, with RR from 0.35 to 0.84 [0.82-0.85]), total cholesterol (4/13 reports from 0.76 [0.59-0.98] to 0.94 [0.90-0.97]; 8/13 reports with non-significant inverse associations), and diastolic blood pressure (2/11 reports from 0.87 [0.78-0.96] to 0.92 [0.85-0.99]; 5/11 reports with non-significant inverse associations), and direct associations for taller height (7/10 reports from 1.03 [1.02-1.05] to 1.92 [1.38-2.67]), which are in the opposite direction of known associations with CHD.,A systematic evaluation of the available evidence suggests similarities as well as important differences in the risk factors for incidence of AF as compared with other cardiovascular diseases, which has implications for the primary prevention strategies for atrial fibrillation. | Different adiposity measures have been associated with increased risk of atrial fibrillation, however, results have previously only been summarized for BMI.,We therefore conducted a systematic review and meta-analysis of prospective studies to clarify the association between different adiposity measures and risk of atrial fibrillation.,PubMed and Embase databases were searched up to October 24th 2016.,Summary relative risks (RRs) were calculated using random effects models.,Twenty-nine unique prospective studies (32 publications) were included.,Twenty-five studies (83,006 cases, 2,405,381 participants) were included in the analysis of BMI and atrial fibrillation.,The summary RR was 1.28 (95% confidence interval: 1.20-1.38, I2 = 97%) per 5 unit increment in BMI, 1.18 (95% CI: 1.12-1.25, I2 = 73%, n = 5) and 1.32 (95% CI: 1.16-1.51, I2 = 91%, n = 3) per 10 cm increase in waist and hip circumference, respectively, 1.09 (95% CI: 1.02-1.16, I2 = 44%, n = 4) per 0.1 unit increase in waist-to-hip ratio, 1.09 (95% CI: 1.02-1.16, I2 = 94%, n = 4) per 5 kg increase in fat mass, 1.10 (95% CI: 0.92-1.33, I2 = 90%, n = 3) per 10% increase in fat percentage, 1.10 (95% CI: 1.08-1.13, I2 = 74%, n = 10) per 5 kg increase in weight, and 1.08 (95% CI: 0.97-1.19, I2 = 86%, n = 2) per 5% increase in weight gain.,The association between BMI and atrial fibrillation was nonlinear, p nonlinearity < 0.0001, with a stronger association at higher BMI levels, however, increased risk was observed even at a BMI of 22-24 compared to 20.,In conclusion, general and abdominal adiposity and higher body fat mass increase the risk of atrial fibrillation.,The online version of this article (doi:10.1007/s10654-017-0232-4) contains supplementary material, which is available to authorized users. | 1 |
Supplemental Digital Content is available in the text.,We aimed to investigate the acute stroke presentations during the coronavirus disease 2019 (COVID-19) pandemic.,The data were obtained from a health system with 19 emergency departments in northeast Ohio in the United States.,Baseline period from January 1 to March 8, 2020, was compared with the COVID period from March 9, to April 2, 2020.,The variables included were total daily stroke alerts across the hospital emergency departments, thrombolysis, time to presentation, stroke severity, time from door-to-imaging, time from door-to-needle in thrombolysis, and time from door-to-puncture in thrombectomy.,The 2 time periods were compared using nonparametric statistics and Poisson regression.,Nine hundred two stroke alerts during the period across the emergency departments were analyzed.,Total daily stroke alerts decreased from median, 10 (interquartile range, 8-13) during baseline period to median, 8 (interquartile range, 4-10, P=0.001) during COVID period.,Time to presentation, stroke severity, and time to treatment were unchanged.,COVID period was associated with decrease in stroke alerts with rate ratio of 0.70 (95% CI, 0.60-0.28).,Thrombolysis also decreased with rate ratio, 0.52 (95% CI, 0.28-0.97) but thrombectomy remained unchanged rate ratio, 0.93 (95% CI, 0.52-1.62),We observed a significant decrease in acute stroke presentations by ≈30% across emergency departments at the time of surge of COVID-19 cases.,This observation could be attributed to true decline in stroke incidence or patients not seeking medical attention for emergencies during the pandemic. | The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center.,On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic.,Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19.,From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona.,We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes.,Data were compared with March 2019 using parametric or nonparametric methods as appropriate.,At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity.,Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426).,Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population.,Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009).,In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge.,The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics.,During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients.,Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic. | 1 |
Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease.,To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19.,The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients.,This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020.,Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein.,There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration.,Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI.,Higher doses of heparin to achieve therapeutic activated clotting times were also noted.,Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission.,In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes.,This supports the need for establishing COVID-19 status in all STEMI cases.,Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases. | Severe pneumonia is pathological manifestation of Coronavirus Disease 2019 (COVID-19), however complications have been reported in COVID-19 patients with a worst prognosis.,Aim of this study was to evaluate the role of high sensitivity cardiac troponin I (hs-TnI) in patients with SARS-CoV-2 infection.,we retrospectively analysed hs-TnI values measured in 523 patients (median age 64 years, 68% men) admitted to a university hospital in Milan, Italy, and diagnosed COVID-19.,A significant difference in hs-TnI concentrations was found between deceased patients (98 patients) vs discharged (425 patients) [36.05 ng/L IQR 16.5-94.9 vs 6.3 ng/L IQR 2.6-13.9, p < 0.001 respectively].,Hs-TnI measurements were independent predictors of mortality at multivariate analysis adjusted for confounding parameters such as age (HR 1.004 for each 10 point of troponin, 95% CI 1.002-1.006, p < 0.001).,The survival rate, after one week, in patients with hs-TnI values under 6 ng/L was 97.94%, between 6 ng/L and the normal value was 90.87%, between the normal value and 40 ng/L was 86.98, and 59.27% over 40 ng/L.,Increase of hs-TnI associated with elevated mortality in patients with COVID-19.,Troponin shows to be a useful biomarker of disease progression and worse prognosis in COVID-19 patients. | 1 |
COVID-19 has rapidly spread around the world and threatened global health.,Although this disease mainly affects the respiratory system, there is increasing evidence that SARS-CoV-2 also has effects on the cardiovascular system.,Echocardiography is a valuable tool in the assessment of cardiovascular disease.,It is cost-effective, widely available and provides information that can influence management.,Given the risk of personnel infection and equipment contamination during echocardiography, leading world societies have recommended performing echocardiography only when a clinical benefit is likely, favouring focussed evaluations and using smaller portable equipment.,In the past months, multiple reports have described a wide pattern of echocardiographic abnormalities in patients with COVID-19.,This review summarises these findings and discusses the possible mechanisms involved. | Supplemental Digital Content is available in the text.,Information on the cardiac manifestations of coronavirus disease 2019 (COVID-19) is scarce.,We performed a systematic and comprehensive echocardiographic evaluation of consecutive patients hospitalized with COVID-19 infection.,One hundred consecutive patients diagnosed with COVID-19 infection underwent complete echocardiographic evaluation within 24 hours of admission and were compared with reference values.,Echocardiographic studies included left ventricular (LV) systolic and diastolic function and valve hemodynamics and right ventricular (RV) assessment, as well as lung ultrasound.,A second examination was performed in case of clinical deterioration.,Thirty-two patients (32%) had a normal echocardiogram at baseline.,The most common cardiac pathology was RV dilatation and dysfunction (observed in 39% of patients), followed by LV diastolic dysfunction (16%) and LV systolic dysfunction (10%).,Patients with elevated troponin (20%) or worse clinical condition did not demonstrate any significant difference in LV systolic function compared with patients with normal troponin or better clinical condition, but they had worse RV function.,Clinical deterioration occurred in 20% of patients.,In these patients, the most common echocardiographic abnormality at follow-up was RV function deterioration (12 patients), followed by LV systolic and diastolic deterioration (in 5 patients).,Femoral deep vein thrombosis was diagnosed in 5 of 12 patients with RV failure.,In COVID-19 infection, LV systolic function is preserved in the majority of patients, but LV diastolic function and RV function are impaired.,Elevated troponin and poorer clinical grade are associated with worse RV function.,In patients presenting with clinical deterioration at follow-up, acute RV dysfunction, with or without deep vein thrombosis, is more common, but acute LV systolic dysfunction was noted in ≈20%. | 1 |
Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body.,To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation.,Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP).,We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations.,Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed. | Vascular calcification is associated with a significant increase in all-cause mortality and atherosclerotic plaque rupture.,Calcification has been determined to be an active process driven in part by vascular smooth muscle cell (VSMC) transdifferentiation within the vascular wall.,Historically, VSMC phenotype switching has been viewed as binary, with the cells able to adopt a physiological contractile phenotype or an alternate ‘synthetic’ phenotype in response to injury.,More recent work, including lineage tracing has however revealed that VSMCs are able to adopt a number of phenotypes, including calcific (osteogenic, chondrocytic, and osteoclastic), adipogenic, and macrophagic phenotypes.,Whilst the mechanisms that drive VSMC differentiation are still being elucidated it is becoming clear that medial calcification may differ in several ways from the intimal calcification seen in atherosclerotic lesions, including risk factors and specific drivers for VSMC phenotype changes and calcification.,This article aims to compare and contrast the role of VSMCs in driving calcification in both atherosclerosis and in the vessel media focusing on the major drivers of calcification, including aging, uraemia, mechanical stress, oxidative stress, and inflammation.,The review also discusses novel findings that have also brought attention to specific pro- and anti-calcifying proteins, extracellular vesicles, mitochondrial dysfunction, and a uraemic milieu as major determinants of vascular calcification. | 1 |
The outbreak of the novel coronavirus in China (SARS‐CoV‐2) that began in December 2019 presents a significant and urgent threat to global health.,This study was conducted to provide the international community with a deeper understanding of this new infectious disease.,Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study.,A total of 135 hospitalized patients with COVID‐19 were enrolled.,The median age was 47 years (interquartile range, 36‐55), and there was no significant gender difference (53.3% men).,The majority of patients had contact with people from the Wuhan area.,Forty‐three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]).,Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]).,Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients.,All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]).,In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]).,It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines.,Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d‐dimer, lactate dehydrogenase, PCT, ALB, C‐reactive protein, and aspartate aminotransferase.,This study demonstrates the clinic features and therapies of 135 COVID‐19 patients.,Kaletra and TCM played an important role in the treatment of the viral pneumonia.,Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID‐19.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.,Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.,Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.,Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.,All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early. | During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed.,We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.,Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China.,Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei.,The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined.,At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort).,The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively.,Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei.,Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity.,However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure.,In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)).,There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre.,Future studies to determine the reason for delaying hospitalisation are warranted.,This study highlights the necessity of urgent and vigorous support of healthcare resources and increased public awareness during the early stages of an outbreak of COVID-19 or similar diseaseshttps://bit.ly/39OWFf0 | 1 |
The association between coronavirus disease 2019 (COVID-19) pneumonia and venous thrombotic disorders is still unclear.,We assessed the association between COVID-19 infection-related pneumonia and proximal deep-vein thrombosis (DVT) in a cohort of patients admitted to our hospital during the European outbreak in the front line of Cremona, Lombardy.,In a single-center cross-sectional study, all patients hospitalized for more than 5 days in Internal Medicine Department with confirmed COVID-19 pneumonia received 2-point compressive ultrasound assessment (CUS) of the leg vein system during a single day.,Ninety-four percent of patients received enoxaparin as standard pharmacological prophylaxis for venous thromboembolism.,The presence of DVT was defined as incompressibility of popliteal or common femoral vein.,Out of 121 patients with COVID-19 pneumonia (mean age 71.8, 66.3% males) hospitalized on March 31st, 70 stayed in hospital for over 5 days and 66 of them underwent CUS of deep venous system of the legs.,The presence of asymptomatic DVT was found in 9 patients (13.6%).,No symptomatic DVT was found.,Patients with DVT showed mean age = 75.7 years, mean D-dimer levels = 4.02 ng/ml and all of them received enoxaparin for thromboprophylaxis, except one.,Computed tomography pulmonary angiogram confirmed pulmonary embolism in five patients.,One every seven patients with COVID-19-related pneumonia, hospitalized for more than 5 days, had asymptomatic proximal DVT and half of them had confirmed PE despite standard pharmacological thromboprophylaxis.,This observational study suggests the need of an active surveillance through CUS in patients hospitalized with acute SARS-COV-2 and underline the need of a more intense thromboprophylaxis. | Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer.,Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19.,To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE.,We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19.,Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR).,There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care.,The diagnostic yield for PE was 37%.,The overall proportion of PE in patients with COVID-19 was 5.4%.,The proportions with Wells score of ≥4 (‘PE likely’) was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951).,The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133).,D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001).,In the ‘low probability’ group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE.,Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common.,Of note, approaching half of PE events were diagnosed on hospital admission.,More data are needed to identify an optimal diagnostic pathway in patients with COVID-19.,Randomised controlled trials of intensified thromboprophylaxis are urgently needed.,•COVID-19 is associated with a higher rate of PE, particularly in critically-ill patients•Identifying those requiring PE imaging is challenging due to overlapping clinical presentation and high D-dimer in COVID-19•Single-centre study of imaging outcomes (for PE), in patients with suspected/confirmed COVID-19•37% of inpatients scanned had PE.,D-dimer >4200 ng/mL risk stratified, but could not exclude PE.,•Clinicians should have high index of suspicion for PE in COVID-19,COVID-19 is associated with a higher rate of PE, particularly in critically-ill patients,Identifying those requiring PE imaging is challenging due to overlapping clinical presentation and high D-dimer in COVID-19,Single-centre study of imaging outcomes (for PE), in patients with suspected/confirmed COVID-19,37% of inpatients scanned had PE.,D-dimer >4200 ng/mL risk stratified, but could not exclude PE.,Clinicians should have high index of suspicion for PE in COVID-19 | 1 |
The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide.,The infection can be life threatening and require intensive care treatment.,The transmission of the disease poses a risk to both patients and healthcare workers.,The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions.,This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic.,To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe.,Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge.,Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described.,In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries.,Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures. | Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | 1 |
Mobile health interventions, especially smartphone applications (apps), have been proposed as promising interventions for supporting adherence to healthy behaviour in patients post cardiac rehabilitation (CR).,The overall aim of the study was to examine the effect of individualized follow-up with an app for one year on peak oxygen uptake (VO2peak) in patients completing CR.,The study was designed as a single-blinded multicentre randomized controlled trial.,The intervention group (IG) received individualized follow-up enabled with an app for one year, while the control group (CG) received usual care.,The primary outcome was difference in VO2peak.,Secondary outcomes included exercise performance (time to exhaustion, peak incline (%) and peak velocity (km/h)), bodyweight, resting blood pressure, lipid profile, triglycerides, exercise habits, health-related quality of life, health status and self-perceived goal achievement.,In total, 113 patients completing CR (73.4% with coronary artery disease, 16.8% after valve surgery and 9.8% with other heart diseases) were randomly allocated to the IG or CG.,Intention to treat analyses showed a statistically significant difference in VO2peak between the groups at follow-up of 2.2 ml/kg/min, 95% confidence interval 0.9-3.5 (p < 0.001).,Statistically significant differences were also observed in exercise performance, exercise habits and in self-perceived goal achievement.,Individualized follow-up for one year with an app significantly improved VO2peak, exercise performance and exercise habits, as well as self-perceived goal achievement, compared with a CG in patients post-CR.,There were no statistically significant differences between the groups at follow-up in the other outcome measures evaluated. | Randomized controlled trials conducted in Mediterranean countries have shown that the Mediterranean diet lowers adverse cardiovascular events.,In the American population, diet remains the biggest uncontrolled risk factor for cardiovascular disease.,This study aimed to test the hypothesis that asynchronous dietary counseling supplied through a custom smartphone app results in better adherence to a Mediterranean diet in a non-Mediterranean population than traditional standard-of-care (SOC) counseling.,In total, 100 patients presenting to the cardiology clinic of an academic medical center were randomized to either the SOC or smartphone app-based experimental (EXP) Mediterranean diet intervention after informed consent and 1 hour of individual face-to-face dietary counseling with a registered dietitian.,Participants in EXP received a custom smartphone app that reinforced the Mediterranean diet, whereas participants in SOC received 2 additional sessions of in-person dietary counseling with the registered dietitian-30 min at 1 month and 30 min at 3 months.,Preexisting knowledge of a Mediterranean diet was measured by the validated Mediterranean Diet Score (MDS) instrument.,Baseline height, weight, blood pressure (BP), and laboratory biomarkers were collected.,At 1, 3, and 6 months, participants presented for a follow-up appointment to assess compliance to the Mediterranean diet using the MDS as well as a patient satisfaction survey, BP, and weight.,Repeat laboratory biomarkers were performed at 3 and 6 months.,Enrolled participants had a mean age with SE of 56.6 (SD 1.7) for SOC and 57.2 (SD 1.8) for EXP; 65.3% of SOC and 56.9% of EXP were male, and 20.4% of SOC and 35.3% of EXP had coronary artery disease.,There were no significant differences between EXP and SOC with regard to BP, lipid parameters, hemoglobin A1c, or C-reactive protein (CRP).,Participants in EXP achieved a significantly greater weight loss on average of 3.3 pounds versus 3.1 pounds for participants in SOC, P=.04.,Adherence to the Mediterranean diet increased significantly over time for both groups (P<.001), but there was no significant difference between groups (P=.69).,Similarly, there was no significant difference in diet satisfaction between EXP and SOC, although diet satisfaction increased significantly over time for both groups.,The proportion of participants with high Mediterranean diet compliance (defined as the MDS ≥9) increased significantly over time (P<.001)-from 18.4% to 57.1% for SOC and 27.5% to 64.7% for EXP; however, there was no significant difference between the groups.,Both traditional SOC counseling and smartphone-based counseling were effective in getting participants to adhere to a Mediterranean diet, and these dietary changes persisted even after counseling had ended.,However, neither method was more effective than the other.,This pilot study demonstrates that patients can change to and maintain a Mediterranean diet with either traditional or smartphone app-based nutrition counseling.,ClinicalTrials.gov NCT03897426;https://clinicaltrials.gov/ct2/show/NCT03897426 | 1 |
Access to quality hypertension care is often poor in sub-Saharan Africa.,Some community pharmacies offer hypertension monitoring services, with and without involvement of medical doctors.,To directly connect pharmacy staff and cardiologists a care model including a mobile application (mHealth) for remote patient monitoring was implemented and pilot tested in Lagos, Nigeria.,Pharmacists provided blood pressure measurements and counselling.,Cardiologists enrolled patients in the pilot program and remotely monitored them, for which patients paid a monthly fee.,We evaluated the feasibility of this care model at five private community pharmacies.,Outcome measures were retention in care, blood pressure change, quality of care, and patients’ and healthcare providers’ satisfaction with the care model.,Patients participated in the care model’s pilot at one of the five pharmacies for approximately 6-8 months from February 2016.,We conducted structured patient interviews and blood pressure measurements at pilot entry and exit, and used exports of the mHealth-application, in-depth interviews and focus group discussions with patients, pharmacists and cardiologists.,Of 336 enrolled patients, 236 (72%) were interviewed at pilot entry and exit.,According to the mHealth data 71% returned to the pharmacy after enrollment, with 3.3 months (IQR: 2.2-5.4) median duration of activity in the mHealth-application.,Patients self-reported more visits than recorded in the mHealth data.,Pharmacists mentioned use of paper records, understaffing, the application not being user-friendly, and patients’ unwillingness to pay as reasons for underreporting.,Mean systolic blood pressure decreased 9.9 mmHg (SD: 18).,Blood pressure on target increased from 24 to 56% and an additional 10% had an improved blood pressure at endline, however this was not associated with duration of mHealth activity.,Patients were satisfied because of accessibility, attention, adherence and information provision.,Patients, pharmacists and cardiologists adopted the care model, albeit with gaps in mHealth data.,Most patients were satisfied, and their mean blood pressure significantly reduced.,Usage of the mHealth application, pharmacy incentives, and a modified financing model are opportunities for improvement.,In addition, costs of implementation and availability of involved healthcare providers need to be investigated before such a care model can be further implemented.,The online version of this article (10.1186/s12913-018-3740-3) contains supplementary material, which is available to authorized users. | The Pan-African Society of Cardiology (PASCAR) has identified hypertension as the highest area of priority for action to reduce heart disease and stroke on the continent.,The aim of this PASCAR roadmap on hypertension was to develop practical guidance on how to implement strategies that translate existing knowledge into effective action and improve detection, treatment and control of hypertension and cardiovascular health in sub-Saharan Africa (SSA) by the year 2025.,Development of this roadmap started with the creation of a consortium of experts with leadership skills in hypertension.,In 2014, experts in different fields, including physicians and non-physicians, were invited to join.,Via faceto- face meetings and teleconferences, the consortium made a situation analysis, set a goal, identified roadblocks and solutions to the management of hypertension and customised the World Heart Federation roadmap to Africa.,Hypertension is a major crisis on the continent but very few randomised, controlled trials have been conducted on its management.,Also, only 25.8% of the countries have developed or adopted guidelines for the management of hypertension.,Other major roadblocks are either government and health-system related or healthcare professional or patient related.,The PASCAR hypertension task force identified a 10-point action plan to be implemented by African ministries of health to achieve 25% control of hypertension in Africa by 2025.,Hypertension affects millions of people in SSA and if left untreated, is a major cause of heart disease and stroke.,Very few SSA countries have a clear hypertension policy.,This PASCAR roadmap identifies practical and effective solutions that would improve detection, treatment and control of hypertension on the continent and could be implemented as is or adapted to specific national settings. | 1 |
Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death.,These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations.,The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients.,Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury.,The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.,•Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,•Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,•Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.,Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification. | Regular exercise has multiple benefits for physical and mental health, including the body’s ability to combat infections.,The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers.,The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period.,The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes. | 1 |
This study provides evidence that m6A methylation is dynamically regulated during human and murine cardiac disease and highlights an important role of the m6A methylase Mettl3 in regulating cardiac growth by gene expression control.,Conceptually similar to modifications of DNA, mRNAs undergo chemical modifications, which can affect their activity, localization, and stability.,The most prevalent internal modification in mRNA is the methylation of adenosine at the N6-position (m6A).,This returns mRNA to a role as a central hub of information within the cell, serving as an information carrier, modifier, and attenuator for many biological processes.,Still, the precise role of internal mRNA modifications such as m6A in human and murine-dilated cardiac tissue remains unknown.,Transcriptome-wide mapping of m6A in mRNA allowed us to catalog m6A targets in human and murine hearts.,Increased m6A methylation was found in human cardiomyopathy.,Knockdown and overexpression of the m6A writer enzyme Mettl3 affected cell size and cellular remodeling both in vitro and in vivo.,Our data suggest that mRNA methylation is highly dynamic in cardiomyocytes undergoing stress and that changes in the mRNA methylome regulate translational efficiency by affecting transcript stability.,Once elucidated, manipulations of methylation of specific m6A sites could be a powerful approach to prevent worsening of cardiac function. | Supplemental Digital Content is available in the text.,N6-Methyladenosine (m6A) methylation is the most prevalent internal posttranscriptional modification on mammalian mRNA.,The role of m6A mRNA methylation in the heart is not known.,To determine the role of m6A methylation in the heart, we isolated primary cardiomyocytes and performed m6A immunoprecipitation followed by RNA sequencing.,We then generated genetic tools to modulate m6A levels in cardiomyocytes by manipulating the levels of the m6A RNA methylase methyltransferase-like 3 (METTL3) both in culture and in vivo.,We generated cardiac-restricted gain- and loss-of-function mouse models to allow assessment of the METTL3-m6A pathway in cardiac homeostasis and function.,We measured the level of m6A methylation on cardiomyocyte mRNA, and found a significant increase in response to hypertrophic stimulation, suggesting a potential role for m6A methylation in the development of cardiomyocyte hypertrophy.,Analysis of m6A methylation showed significant enrichment in genes that regulate kinases and intracellular signaling pathways.,Inhibition of METTL3 completely abrogated the ability of cardiomyocytes to undergo hypertrophy when stimulated to grow, whereas increased expression of the m6A RNA methylase METTL3 was sufficient to promote cardiomyocyte hypertrophy both in vitro and in vivo.,Finally, cardiac-specific METTL3 knockout mice exhibit morphological and functional signs of heart failure with aging and stress, showing the necessity of RNA methylation for the maintenance of cardiac homeostasis.,Our study identified METTL3-mediated methylation of mRNA on N6-adenosines as a dynamic modification that is enhanced in response to hypertrophic stimuli and is necessary for a normal hypertrophic response in cardiomyocytes.,Enhanced m6A RNA methylation results in compensated cardiac hypertrophy, whereas diminished m6A drives eccentric cardiomyocyte remodeling and dysfunction, highlighting the critical importance of this novel stress-response mechanism in the heart for maintaining normal cardiac function. | 1 |
Optimally treated heart failure (HF) patients often have persisting symptoms and poor health-related quality of life.,Comorbidities are common, but little is known about their impact on these factors, and guideline-driven HF care remains focused on cardiovascular status.,The following hypotheses were tested: (i) comorbidities are associated with more severe symptoms and functional limitations and subsequently worse patient-rated health in HF, and (ii) these patterns of association differ among selected comorbidities.,The Swedish Heart Failure Registry (SHFR) is a national population-based register of HF patients admitted to >85% of hospitals in Sweden or attending outpatient clinics.,This study included 10,575 HF patients with patient-rated health recorded during first registration in the SHFR (1 February 2008 to 1 November 2013).,An a priori health model and sequences-of-regressions analysis were used to test associations among comorbidities and patient-reported symptoms, functional limitations, and patient-rated health.,Patient-rated health measures included the EuroQol-5 dimension (EQ-5D) questionnaire and the EuroQol visual analogue scale (EQ-VAS).,EQ-VAS score ranges from 0 (worst health) to 100 (best health).,Patient-rated health declined progressively from patients with no comorbidities (mean EQ-VAS score, 66) to patients with cardiovascular comorbidities (mean EQ-VAS score, 62) to patients with non-cardiovascular comorbidities (mean EQ-VAS score, 59).,The relationships among cardiovascular comorbidities and patient-rated health were explained by their associations with anxiety or depression (atrial fibrillation, odds ratio [OR] 1.16, 95% CI 1.06 to 1.27; ischemic heart disease [IHD], OR 1.20, 95% CI 1.09 to 1.32) and with pain (IHD, OR 1.25, 95% CI 1.14 to 1.38).,Associations of non-cardiovascular comorbidities with patient-rated health were explained by their associations with shortness of breath (diabetes, OR 1.17, 95% CI 1.03 to 1.32; chronic kidney disease [CKD, OR 1.23, 95% CI 1.10 to 1.38; chronic obstructive pulmonary disease [COPD], OR 95% CI 1.84, 1.62 to 2.10) and with fatigue (diabetes, OR 1.27, 95% CI 1.13 to 1.42; CKD, OR 1.24, 95% CI 1.12 to 1.38; COPD, OR 1.69, 95% CI 1.50 to 1.91).,There were direct associations between all symptoms and patient-rated health, and indirect associations via functional limitations.,Anxiety or depression had the strongest association with functional limitations (OR 10.03, 95% CI 5.16 to 19.50) and patient-rated health (mean difference in EQ-VAS score, −18.68, 95% CI −23.22 to −14.14).,HF optimizing therapies did not influence these associations.,Key limitations of the study include the cross-sectional design and unclear generalisability to other populations.,Further prospective HF studies are required to test the consistency of the relationships and their implications for health.,Identification of distinct comorbidity health pathways in HF could provide the evidence for individualised person-centred care that targets specific comorbidities and associated symptoms.,Using cross-sectional data from the Swedish Heart Failure Registry, Claire Lawson and colleagues examine the comorbidity patient-rated health pathways in heart failure patients | Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce.,We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014.,For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex.,Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months.,For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region.,We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates.,We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years).,From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94).,However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age.,The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616).,Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1).,Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference −3·51 years, 95% CI −3·77 to −3·25).,From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened.,Socioeconomically deprived individuals also had more comorbidities, despite their younger age.,Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined.,The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled.,British Heart Foundation and National Institute for Health Research. | 1 |
Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment.,However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported.,This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease.,Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients.,Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes.,Elevated inflammatory markers and evidence of cytokine storm were frequently observed.,A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation.,Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%.,Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase.,Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.,Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection.,Evidence is still scarce but rapidly emerging in the literature.,Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time.What is Known:• Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2.,What is New:• Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock.,• Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias.,• Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation.,• Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.,What is Known:,• Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2.,What is New:,• Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock.,• Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias.,• Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation.,• Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.,The online version of this article (10.1007/s00431-020-03766-6) contains supplementary material, which is available to authorized users. | Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia.,Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.,A 63-year-old male was admitted with pneumonia and cardiac symptoms.,He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission.,He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography.,The highest level of interleukin-6 was 272.40 pg/ml.,Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia.,Laboratory test results for viruses that cause myocarditis were all negative.,The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis.,After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL.,Moreover, the LVEF of the patient gradually recovered to 68%.,The patient died of aggravation of secondary infection on the 33rd day of hospitalization.,COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure.,This is the first report of COVID-19 complicated with fulminant myocarditis.,The mechanism of cardiac pathology caused by COVID-19 needs further study. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19. | 1 |
Visual impairment from diabetic retinopathy (DR) is an increasing global public health concern, which is preventable with screening and early treatment.,Digital retinal imaging has become a preferred choice as it enables higher coverage of screening.,The aim of this review is to evaluate how different characteristics of the DR screening (DRS) test impact on diagnostic test accuracy (DTA) and its relevance to a low-income setting.,We conducted a systematic literature search to identify clinic-based studies on DRS using digital retinal imaging of people with DM (PwDM).,Summary estimates of different sub-groups were calculated using DTA values weighted according to the sample size.,The DTA of each screening method was derived after exclusion of ungradable images and considering the eye as the unit of analysis.,The meta-analysis included studies which measured DTA of detecting any level of DR.,We also examined the effect on detection from using different combinations of retinal fields, pupil status, index test graders and setting.,Six thousand six hundred forty-six titles and abstracts were retrieved, and data were extracted from 122 potentially eligible full reports.,Twenty-six studies were included in the review, and 21 studies, mostly from high-income settings (18/21, 85.7%), were included in the meta-analysis.,The highest sensitivity was observed in the mydriatic greater than two field strategy (92%, 95% CI 90-94%).,The highest specificity was observed in greater than two field methods (94%, 95% CI 93-96%) where mydriasis did not affect specificity.,Overall, there was no difference in sensitivity between non-mydriatic and mydriatic methods (86%, 95% CI 85-87) after exclusion of ungradable images.,The highest DTA (sensitivity 90%, 95% CI 88-91%; specificity 95%, 95% CI 94-96%) was observed when screening was delivered at secondary/tertiary level clinics.,Non-mydriatic two-field strategy could be a more pragmatic approach in starting DRS programmes for facility-based PwDM in low-income settings, with dilatation of the pupils of those who have ungradable images.,There was insufficient evidence in primary studies to draw firm conclusions on how graders’ background influences DTA.,Conducting more context-specific DRS validation studies in low-income and non-ophthalmic settings can be recommended.,The online version of this article (10.1186/s13643-018-0846-y) contains supplementary material, which is available to authorized users. | The aim of this study is to analyze the yield of retinal images obtained in a rural diabetes eye care model.,An analysis of a sample of nonmydriatic fundus photography (NMFP) of posterior segment ophthalmic images, obtained by an indigenous equipment (3 nethra-Forus Royal), was done in a district-wide rural diabetic retinopathy (DR) screening program; a trained optometrist did the initial image grading.,DR and diabetic macular edema (DME) were classified based on international DR and DME severity scale.,The agreement between the optometrist and retina specialist was very good (κ = 0.932; standard error = 0.030; 95% confidence interval = 0.874-0.991).,Posterior segment images of 2000 eyes of 1000 people with diabetes mellitus (DM) were graded.,The mean age of the participants was 55.7 ± 11.5 standard deviation years.,Nearly 42% of the screened participants (n = 420/1000) needed referral.,The most common referable posterior segment abnormality was DR (8.2%).,The proportion of people with any form of DR was seen in 110/1225 eyes, and sight-threatening DR was seen in 35/1225 eyes.,About 62% of posterior segment images were gradable.,The reasons for ungradable posterior segment images (34%) were small pupil, unfocused/partially available field of images, and cataract.,A NMFP model was able to detect referable posterior segment abnormalities in a rural diabetes eye care program.,Reasons found for ungradability of images in the present study can be addressed while designing future DR screening programs in the rural areas. | 1 |
Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer.,Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19.,To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE.,We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19.,Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR).,There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care.,The diagnostic yield for PE was 37%.,The overall proportion of PE in patients with COVID-19 was 5.4%.,The proportions with Wells score of ≥4 (‘PE likely’) was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951).,The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3-9) in PE group vs 4 (IQR 2-7) in those without PE (P = 0.133).,D-dimer was higher in PE (median 8000 ng/mL; IQR 4665-8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210-4410 ng/mL, P < 0.001).,In the ‘low probability’ group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE.,Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common.,Of note, approaching half of PE events were diagnosed on hospital admission.,More data are needed to identify an optimal diagnostic pathway in patients with COVID-19.,Randomised controlled trials of intensified thromboprophylaxis are urgently needed.,•COVID-19 is associated with a higher rate of PE, particularly in critically-ill patients•Identifying those requiring PE imaging is challenging due to overlapping clinical presentation and high D-dimer in COVID-19•Single-centre study of imaging outcomes (for PE), in patients with suspected/confirmed COVID-19•37% of inpatients scanned had PE.,D-dimer >4200 ng/mL risk stratified, but could not exclude PE.,•Clinicians should have high index of suspicion for PE in COVID-19,COVID-19 is associated with a higher rate of PE, particularly in critically-ill patients,Identifying those requiring PE imaging is challenging due to overlapping clinical presentation and high D-dimer in COVID-19,Single-centre study of imaging outcomes (for PE), in patients with suspected/confirmed COVID-19,37% of inpatients scanned had PE.,D-dimer >4200 ng/mL risk stratified, but could not exclude PE.,Clinicians should have high index of suspicion for PE in COVID-19 | •COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,•Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,•Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low.,COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low. | 1 |
With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19. | Acute stroke remains a medical emergency even during the COVID-19 pandemic.,Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations.,Here we present a series of four patients with COVID-19 that presented with acute stroke.,We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection.,All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study.,Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study.,Retrospective patient data were obtained from electronic medical records.,Informed consent was obtained.,We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection.,We elucidate the clinical characteristics, imaging findings, and the clinical course.,Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke.,Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should don appropriate personal protective equipment in every suspected patient.,Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection. | 1 |
The coronavirus disease 2019 (COVID-19) outbreak, along with implementation of lockdown and strict public movement restrictions, in Greece has affected hospital visits and admissions.,We aimed to investigate trends of cardiac disease admissions during the outbreak of the pandemic and possible associations with the applied restrictive measures.,This is a retrospective observational study.,Data for 4970 patients admitted via the cardiology emergency department (ED) across 3 large-volume urban hospitals in Athens and 2 regional/rural hospitals from February 3, 2020, up to April 12 were recorded.,Data from the equivalent (for the COVID-19 outbreak) time period of 2019 and from the postlockdown time period were also collected.,A falling trend of cardiology ED visits and hospital admissions was observed starting from the week when the restrictive measures due to COVID-19 were implemented.,Compared with the pre-COVID-19 outbreak time period, acute coronary syndrome (ACS) [145 (29/week) vs. 60 (12/week), −59%, P < 0.001], ST elevation myocardial infarction [46 (9.2/week) vs.,21 (4.2/week), −54%, P = 0.002], and non-ST elevation ACS [99 cases (19.8/week) vs.,39 (7.8/week), −60% P < 0.001] were reduced at the COVID-19 outbreak time period.,Reductions were also noted for heart failure worsening and arrhythmias.,The ED visits in the postlockdown period were significantly higher than in the COVID-19 outbreak time period (1511 vs 660; P < 0.05).,Our data show significant drops in cardiology visits and admissions during the COVID-19 outbreak time period.,Whether this results from restrictive measures or depicts a true reduction of cardiac disease cases warrants further investigation.,•The coronavirus disease 2019 (COVID-19) outbreak has led to an unprecedented health system overload.,•The restrictive measures in Greece resulted in a low number of COVID-19 cases.,•Hospital visits and cardiovascular events have diminished after implementation of restrictive measures.,•Acute coronary syndromes reduced by approximately 55%, despite limited incidence of COVID-19.,•The multifactorial etiology of this finding should be thoroughly investigated.,The coronavirus disease 2019 (COVID-19) outbreak has led to an unprecedented health system overload.,The restrictive measures in Greece resulted in a low number of COVID-19 cases.,Hospital visits and cardiovascular events have diminished after implementation of restrictive measures.,Acute coronary syndromes reduced by approximately 55%, despite limited incidence of COVID-19.,The multifactorial etiology of this finding should be thoroughly investigated. | Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc).,To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals.,At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ.,Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy.,We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group).,A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days.,The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001).,One patient per group suffered a malignant ventricular arrhythmia.,Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days.,The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time. | 1 |
Previous studies has shown a significant relationship between baseline triglyceride-glucose (TyG) index and subsequent cardiovascular disease (CVD).,However, the effect of longitudinal changes in TyG index on the risk of CVD remains uncertain.,This study aimed to investigate the association between change in TyG index and the risk of CVD in the general population.,The current study included 62,443 Chinese population who were free of CVD.,The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2], and change in TyG index was defined as the difference between the TyG index in 2010 and that in 2006.,Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to examine the association between change in TyG index and the risk of CVD.,During a median follow-up of 7.01 years, 2530 (4.05%) incident CVD occurred, including 2018 (3.23%) incident stroke and 545 (0.87%) incident myocardial infarction (MI).,The risk of developing CVD increased with the quartile of change in TyG index, after adjustment for multiple potential confounders, the hazard ratios for the Q4 group versus the Q1 group were 1.37 (95% confidence interval [CI], 1.21-1.54) for the overall CVD, 1.38 (95% CI, 1.19-1.60) for stroke, and 1.36 (95% CI, 1.05-1.76) for MI.,Restricted cubic spline analysis also showed a cumulative increase in the risk of CVD with increases in the magnitude of change in TyG index.,The addition of change in TyG index to a baseline risk model for CVD improved the C-statistics (P = 0.0097), integrated discrimination improvement value (P < 0.0001), and category-free net reclassification improvement value (P < 0.0001).,Similar results were observed for stroke and MI.,Substantial changes in TyG index independently predict the risk of CVD in the general population.,Monitoring long-term changes in TyG may assist with in the early identification of individuals at high risk of CVD.,The online version contains supplementary material available at 10.1186/s12933-021-01305-7. | Data on the relationship between the triglyceride glucose (TyG) index and coronary artery calcification (CAC) progression is limited.,This longitudinal study evaluated the association of TyG index with CAC progression in asymptomatic adults.,We enrolled 12,326 asymptomatic Korean adults who had at least two CAC evaluations.,The TyG index was determined using ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2).,CAC progression was defined as a difference ≥ 2.5 between the square roots (√) of the baseline and follow-up coronary artery calcium score (CACS) (Δ√transformed CACS).,Annualized Δ√transformed CACS was defined as Δ√transformed CACS divided by the inter-scan period.,During a mean 3.3 years, the overall incidence of CAC progression was 30.6%.,The incidence of CAC progression (group I [lowest]: 22.7% versus [vs.] group II: 31.7% vs. group III [highest]: 37.5%, P < 0.001) and annualized Δ√transformed CACS (group I: 0.46 ± 1.44 vs. group II: 0.71 ± 2.02 vs. group III: 0.87 ± 1.75, P < 0.001) were markedly elevated with increasing TyG index tertiles.,Multivariate linear regression analysis showed that TyG index was associated with annualized Δ√transformed CACS (β = 0.066, P = 0.036).,In multivariate logistic regression analysis, the TyG index was significantly associated with CAC progression in baseline CACS ≤ 100.,The TyG index is an independent predictor of CAC progression, especially in adults without heavy baseline CAC. | 1 |
Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19. | We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia. | 1 |
Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs.,Whole-body autopsy studies of COVID-19 patients have been sparse.,To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy.,Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined.,Only lung tissues were subject to transmission electron microscopy.,COVID-19 caused multisystem pathology.,Pulmonary and cardiovascular involvement were dominant pathological features.,Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected.,These findings were similar in patients with or without preexisting medical comorbidities.,SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities.,Autopsy findings in patients with COVID-19 showed deaths were due to cardiorespiratory failure, predominantly caused by acute lung injury, microvascular damage, and thrombosis.,COVID-19 causes multisystem disease and significant pathology in most organs in patients with and without comorbidities. | An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health. | 1 |
The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity.,We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality.,We also carried out an updated meta-analysis on the relevant studies.,We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020.,The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not.,Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.,Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively.,Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR = 0.89, 0.67-1.19 for ACE-I and ARB, respectively).,Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78-1.26 and HR = 0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group.,Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association.,In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients. | Controversy has arisen in the scientific community on whether the use of renin‐angiotensin system (RAS) inhibitors in the context of COVID‐19 would be beneficial or harmful.,A meta‐analysis of eligible studies comparing the occurrence of severe and fatal COVID‐19 in infected hypertensive patients who were under treatment with angiotensin‐converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted.,PubMed, Google Scholar, the Cochrane Library, medRxiv and bioRxiv were searched for relevant studies.,Fixed‐effects models or random‐effects models were used depending on the heterogeneity between estimates.,A total of eighteen studies with 17 311 patients were included.,The use of RAS inhibitors was associated with a significant 16% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR: 0.84 (95% CI: 0.73‐0.95), P = .007, I2 = 65%.,The results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis of COVID‐19, and could even be protective in hypertensive subjects.,Hypertensive patients should continue these drugs even if they become infected with SARS‐CoV‐2.,Controversy exists on whether RAS inhibitors are beneficial or harmful in COVID‐19.,In this meta‐analysis, the use of RAS inhibitors was not associated with a worse COVID‐19 prognosis and was even protective in hypertensive patients.,Patients should continue these drugs during their COVID‐19 illness. | 1 |
Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19.,These data include elevated D-dimers observed among many COVID-19 patients.,We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals.,The primary outcome was all-cause mortality.,Secondary outcomes were intubation and venous thromboembolism (VTE).,Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE.,Using Cox proportional-hazard modeling, each 1 μg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04-1.08, p < 0.0001) for death, 1.08 (95%CI 1.06-1.10, p < 0.0001) for intubation, and 1.08 (95%CI 1.03-1.13, p = 0.0087) for VTE.,Time-dependent receiver-operator-curves for admission D-dimer as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.694, 0.621, and 0.565 respectively.,Joint-latent-class-modeling identified distinct groups of patients with respect to D-dimer trend.,Patients with stable D-dimer trajectories had HRs of 0.29 (95%CI 0.17-0.49, p < 0.0001) and 0.22 (95%CI 0.10-0.45, p = 0.0001) relative to those with increasing D-dimer trajectories, for the outcomes death and intubation respectively.,Patients with low-increasing D-dimer trajectories had a multivariable HR for VTE of 0.18 (95%CI 0.05-0.68, p = 0.0117) relative to those with high-decreasing D-dimer trajectories.,Time-dependent receiver-operator-curves for D-dimer trend as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.678, 0.699, and 0.722 respectively.,Although admission D-dimer levels, and D-dimer trends, are associated with outcomes in COVID-19, they have limited performance characteristics as prognostic tests.,•We present a retrospective analysis of admission D-dimer, and D-dimer trends, among adults hospitalized for COVID-19.•1065 inpatients from 6 hospitals were included; outcomes included mortality, intubation, and VTE.,•Admission D-dimers and D-dimer trends were associated with outcomes in COVID-19.,•However, D-dimer levels and trends were limited prognostic tests in COVID-19.,•The role of D-dimer levels in COVID-19 clinical decision making remains unclear.,We present a retrospective analysis of admission D-dimer, and D-dimer trends, among adults hospitalized for COVID-19.,1065 inpatients from 6 hospitals were included; outcomes included mortality, intubation, and VTE.,Admission D-dimers and D-dimer trends were associated with outcomes in COVID-19.,However, D-dimer levels and trends were limited prognostic tests in COVID-19.,The role of D-dimer levels in COVID-19 clinical decision making remains unclear. | Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients. | 1 |
Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19).,To evaluate the incidence of VTE in patients with COVID-19.,MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19.,Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis.,3487 patients from 30 studies were included.,Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%-66%).,PE with or without DVT occurred in 12% of patients (95% PI, 2%-46%) and DVT alone in 14% (95% PI, 1%-75%).,Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%-57%) and DVT in 6% (95% PI, 0%-60%), compared to 11% (95% PI, 2%-46%) and 24% (95% PI, 2%-85%) in studies using other diagnostic strategies or patient sampling.,In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%-66%), PE in 19% (95% PI, 6%-47%), and DVT alone in 7% (95% PI, 0%-69%).,Corresponding values in general wards were respectively 9% (95% PI, 0%-94%), 4% (95% PI, 0%-100%), and 7% (95% CI, 1%-49%).,VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE.,The threshold for clinical suspicion should be low to trigger prompt diagnostic testing.,•Incidence of venous thromboembolism (VTE) in Coronavirus Disease-2019 (COVID-19) is unclear.,•A total of 3487 patients with COVID-19 were included in 30 observational studies.,•VTE incidence varied due to differences in diagnostic protocols and hospital setting.,•VTE risk was higher in intensive care units, but seemed also substantial in general wards despite prophylaxis.,Incidence of venous thromboembolism (VTE) in Coronavirus Disease-2019 (COVID-19) is unclear.,A total of 3487 patients with COVID-19 were included in 30 observational studies.,VTE incidence varied due to differences in diagnostic protocols and hospital setting.,VTE risk was higher in intensive care units, but seemed also substantial in general wards despite prophylaxis. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019.,During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy.,Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer.,Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke. | Since the onset of the coronavirus 2019 (COVID-19) pandemic, doctors and public authorities have demonstrated concern about the reduction in quality of care for other health conditions due to social restrictions and lack of resources.,Using a population-based stroke registry, we investigated the impact of the onset of the COVID-19 pandemic in stroke admissions in Joinville, Brazil.,Patients admitted after the onset of COVID-19 restrictions in the city (defined as March 17, 2020) were compared with those admitted in 2019.,We analyzed differences between stroke incidence, types, severity, reperfusion therapies, and time from stroke onset to admission.,Statistical tests were also performed to compare the 30 days before and after COVID-19 to the same period in 2019.,We observed a decrease in total stroke admissions from an average of 12.9/100 000 per month in 2019 to 8.3 after COVID-19 (P=0.0029).,When compared with the same period in 2019, there was a 36.4% reduction in stroke admissions.,There was no difference in admissions for severe stroke (National Institutes of Health Stroke Scale score >8), intraparenchymal hemorrhage, and subarachnoid hemorrhage.,The onset of COVID-19 was correlated with a reduction in admissions for transient, mild, and moderate strokes.,Given the need to prevent the worsening of symptoms and the occurrence of medical complications in these groups, a reorganization of the stroke-care networks is necessary to reduce collateral damage caused by COVID-19. | 1 |
An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported.,Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown.,We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.,In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS).,The study was approved by the Institutional Ethics Committee.,The study comprised 156 patients (65.4% male).,All but three patients received standard doses of thromboprophylaxis.,Median days of hospitalization until CCUS was 9 (IQR 5-17).,CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT.,Seven patients (4.5%) had bilateral distal DVT.,Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001.,D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1).,D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84).,In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.,What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?,All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study.,Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events.,The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.,Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%).,Pulmonary embolism accounted for 52% of the recorded TCs.,High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).,High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage.,Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.,ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov | At the end of last year, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an acute respiratory illness epidemic in Wuhan, China [1, 2].,The World Health Organization (WHO) termed this illness coronavirus disease 2019 (COVID-19).,The coronavirus family have been shown to enter cells through binding angiotensin-converting enzyme 2 (ACE-2), found mainly on alveolar epithelium and endothelium.,Activation of endothelial cells is thought to be the primary driver for the increasingly recognised complication of thrombosis.,Pulmonary thrombosis appears to be common in COVID-19 pneumonia and takes two forms, proximal pulmonary emboli and/or distal thrombosis.,The possible mechanisms and clinical implications are discussed.https://bit.ly/372Xdhw | 1 |
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens.,Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self.,An example of a sterile injury is myocardial infarction (MI).,We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens.,DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs.,In steady state, cardiac self-antigen α-myosin was presented in the heart-draining mediastinal lymph node (mLN) by cDC1s, driving the proliferation of antigen-specific CD4+ TCR-M T cells and their differentiation into regulatory cells (Tregs).,Following MI, all DC subsets infiltrated the heart, whereas only cDCs migrated to the mLN.,Here, cDC2s induced TCR-M proliferation and differentiation into interleukin-(IL)-17/interferon-(IFN)γ-producing effector cells.,Thus, cardiac-specific autoreactive T cells get activated by mature DCs following myocardial infarction.,•IRF8+ cDC1, IRF4+ cDC2, moDCs, and macrophages are the APCs of the murine heart•Self-antigen presentation in the steady state drives Treg development via cDC1s•Myocardial infarction promotes infiltration, activation, and maturation of all DCs•Myocardial infarction promotes priming of Th1/Th17 autoreactive T cells via cDC2s,IRF8+ cDC1, IRF4+ cDC2, moDCs, and macrophages are the APCs of the murine heart,Self-antigen presentation in the steady state drives Treg development via cDC1s,Myocardial infarction promotes infiltration, activation, and maturation of all DCs,Myocardial infarction promotes priming of Th1/Th17 autoreactive T cells via cDC2s,Van der Borght et al. demonstrate that myocardial infarction induces the priming of autoreactive CD4+ T cells specific for cardiac self-antigen α-myosin in the heart-draining lymph node through the maturation and migration of conventional dendritic cells.,Using ex vivo co-culture systems, cDC2s are shown to be superior in presenting α-myosin. | Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction.,Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h.,Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction.,Monocytes would transdifferentiate into macrophages after transmigrating into the infarct area.,Both neutrophils and monocytes-derived macrophages are known to release proteases and cytokines that are detrimental to the surviving cardiomyocytes.,Paradoxically, these inflammatory cells also play critical roles in repairing the injured myocardium.,Depletion of either neutrophils or monocytes do not improve overall cardiac function after myocardial infarction.,Instead, the left ventricular function is further impaired and cardiac fibrosis persists.,Moreover, the inflammatory microenvironment created by the infiltrated neutrophils and monocytes-derived macrophages is essential for the recruitment of cardiac progenitor cells.,Recent studies also suggest that treatment with anti-inflammatory drugs may cause cardiac dysfunction after injury.,Indeed, clinical studies have shown that traditional ant-inflammatory strategies are ineffective to improve cardiac function after infarction.,Thus, the focus should be on how to harness these inflammatory events to either improve the efficacy of the delivered drugs or to favor the recruitment of cardiac progenitor cells. | 1 |
Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
What is the prevalence of dyslipidemia in Chinese adults and what are the treatment and control rates of elevated low-density lipoprotein cholesterol in both primary and secondary prevention populations?,In this cross-sectional study of 2 314 538 community residents, 33.8% had dyslipidemia, 3.2% had established atherosclerotic cardiovascular disease (ASCVD), and 10.2% had high risk of ASCVD; 26.6% of those with ASCVD and 42.9% of those at high risk of ASCVD achieved low-density lipoprotein cholesterol control targets.,Statins were available in 49.7% of the primary care institutions surveyed, with the lowest availability in rural village clinics.,These findings suggest that dyslipidemia has become a major public health problem in China and is often inadequately treated and uncontrolled.,This cross-sectional study assesses the prevalence, treatment, and control of dyslipidemia in community residents and the availability of lipid-lowering medications in primary care institutions in China.,Dyslipidemia, the prevalence of which historically has been low in China, is emerging as the second leading yet often unaddressed factor associated with the risk of cardiovascular diseases.,However, recent national data on the prevalence, treatment, and control of dyslipidemia are lacking.,To assess the prevalence, treatment, and control of dyslipidemia in community residents and the availability of lipid-lowering medications in primary care institutions in China.,This cross-sectional study used data from the China-PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, which enrolled 2 660 666 community residents aged 35 to 75 years from all 31 provinces in China between December 2014 and May 2019, and the China-PEACE primary health care survey of 3041 primary care institutions.,Data analysis was performed from June 2019 to March 2021.,Study period.,The main outcome was the prevalence of dyslipidemia, which was defined as total cholesterol greater than or equal to 240 mg/dL, low-density lipoprotein cholesterol (LDL-C) greater than or equal to 160 mg/dL, high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL, triglycerides greater than or equal to 200 mg/dL, or self-reported use of lipid-lowering medications, in accordance with the 2016 Chinese Adult Dyslipidemia Prevention Guideline.,This study included 2 314 538 participants with lipid measurements (1 389 322 women [60.0%]; mean [SD] age, 55.8 [9.8] years).,Among them, 781 865 participants (33.8%) had dyslipidemia.,Of 71 785 participants (3.2%) who had established atherosclerotic cardiovascular disease (ASCVD) and were recommended by guidelines for lipid-lowering medications regardless of LDL-C levels, 10 120 (14.1%) were treated.,The overall control rate of LDL-C (≤70 mg/dL) among adults with established ASCVD was 26.6% (19 087 participants), with the control rate being 44.8% (4535 participants) among those who were treated and 23.6% (14 552 participants) among those not treated.,Of 236 579 participants (10.2%) with high risk of ASCVD, 101 474 (42.9%) achieved LDL-C less than or equal to 100 mg/dL.,Among participants with established ASCVD, advanced age (age 65-75 years, odds ratio [OR], 0.63; 95% CI, 0.56-0.70), female sex (OR, 0.56; 95% CI, 0.53-0.58), lower income (reference category), smoking (OR, 0.89; 95% CI, 0.85-0.94), alcohol consumption (OR, 0.87; 95% CI, 0.83-0.92), and not having diabetes (reference category) were associated with lower control of LDL-C.,Among participants with high risk of ASCVD, younger age (reference category) and female sex (OR, 0.58; 95% CI, 0.56-0.59) were associated with lower control of LDL-C.,Of 3041 primary care institutions surveyed, 1512 (49.7%) stocked statin and 584 (19.2%) stocked nonstatin lipid-lowering drugs.,Village clinics in rural areas had the lowest statin availability.,These findings suggest that dyslipidemia has become a major public health problem in China and is often inadequately treated and uncontrolled.,Statins were available in less than one-half of the primary care institutions.,Strategies aimed at detection, prevention, and treatment are needed. | Dyslipidemia is a modifiable risk factor for cardiovascular disease (CVD).,We investigated the prevalence and associated risk factors of dyslipidemia- raised total cholesterol (TC), raised triglycerides (TG), raised low-density lipoprotein (LDL-C), low high-density lipoprotein (HDL-C), and raised non-high-density lipoprotein (non-HDL-C) in rural and urban China.,We analyzed data from 136,945 participants aged 40-100 years of the CNSSPP project for 2014.,Dyslipidemia was defined by the NCEP-ATP III and the 2016 Chinese guidelines for the management of dyslipidemia in adults.,Complete data on demographic, metabolic and lifestyle characteristics were used.,Chi-square tests and multivariable logistic regression were used to obtain age- and sex-adjusted prevalence and risk factors for dyslipidemia among participants.,A total of 53.1% participants lived in rural areas.,The prevalence of dyslipidemia was similar among rural and urban participants (43.2% vs.,43.3%).,Regarding the components of dyslipidemia: urban compared with rural participants had a higher prevalence of low HDL-C (20.8% vs.,19.2%), whereas the prevalence of raised LDL-C (7.8% vs.,8.3%), raised TC (10.9% vs.11.8%) and raised non-HDL-C (10.0% vs.,10.9%) were lower in urban residents, (all p < 0.001).,Women were more likely to have raised TC than men (adjusted OR [AOR] =1.83, 95% confidence interval [CI]:1.75-1.91), raised LDL-C (AOR = 1.55, 95% CI: 1.47-1.63) and high non-HDL-C (AOR = 1.52 95% CI: 1.45-1.59) (all p < 0.001).,Compared with rural, urban participants had higher odds of dyslipidemia: low HDL-C (AOR = 1.04, 95% CI: 1.01-1.07), and raised TG (AOR = 1.06, 95% CI: 1.04-1.09).,Hypertension and current drinker were less likely to get low HDL-C with AOR 0.93 (95% CI: 0.90-0.96) and AOR 0.73 (95% CI: 0.70-75), respectively.,Overweight, obesity, central obesity and diabetes had higher odds of all dyslipidemias (p < 0.001).,Low HDL-C was higher in urban areas, whereas the remaining dyslipidemia types were more common in rural areas.,Dyslipidemia was more common in women in both areas of residence.,Overweight, obesity, central obesity and diabetes were associated with dyslipidemias.,The need to intensify intervention programs to manage dyslipidemia and risk factors should be prioritized. | 1 |
Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability.,This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019.,GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019.,Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019.,The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period.,The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019.,The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019.,Cardiovascular diseases remain the leading cause of disease burden in the world.,CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries.,There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.,•The burden of CVD, in number of DALYs and deaths, continues to increase globally.,•CVD burden attributable to modifiable risk factors continues to increase globally.,•Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.,The burden of CVD, in number of DALYs and deaths, continues to increase globally.,CVD burden attributable to modifiable risk factors continues to increase globally.,Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD. | Ischemic heart disease and myocardial infarction remain leading causes of mortality worldwide.,Existing myocardial infarction treatments are incapable of fully repairing and regenerating the infarcted myocardium.,Stem cell transplantation therapy has demonstrated promising results in improving heart function following myocardial infarction.,However, poor cell survival and low engraftment at the harsh and hostile environment at the site of infarction limit the regeneration potential of stem cells.,Preconditioning with various physical and chemical factors, as well as genetic modification and cellular reprogramming, are strategies that could potentially optimize stem cell transplantation therapy for clinical application.,In this review, we discuss the most up-to-date findings related to utilizing preconditioned stem cells for myocardial infarction treatment, focusing mainly on preconditioning with hypoxia, growth factors, drugs, and biological agents.,Furthermore, genetic manipulations on stem cells, such as the overexpression of specific proteins, regulation of microRNAs, and cellular reprogramming to improve their efficiency in myocardial infarction treatment, are discussed as well. | 1 |
•Venous thrombosis is common in patients with severe COVID-19 pneumonia.,•Many of these thromboses may be immunothromboses due to local inflammation, rather than thromboembolic disease.,•Anticoagulated patients with COVID-19 pneumonia have a risk of major bleeding.,Venous thrombosis is common in patients with severe COVID-19 pneumonia.,Many of these thromboses may be immunothromboses due to local inflammation, rather than thromboembolic disease.,Anticoagulated patients with COVID-19 pneumonia have a risk of major bleeding. | The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19. | 1 |
Mitochondria are key regulators of cell fate through controlling ATP generation and releasing pro-apoptotic factors.,Cardiac ischemia/reperfusion (I/R) injury to the coronary microcirculation has manifestations ranging in severity from reversible edema to interstitial hemorrhage.,A number of mechanisms have been proposed to explain the cardiac microvascular I/R injury including edema, impaired vasomotion, coronary microembolization, and capillary destruction.,In contrast to their role in cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues.,It is clear that abnormal mitochondrial signatures, including mitochondrial oxidative stress, mitochondrial fission, mitochondrial fusion, and mitophagy, play a substantial role in endothelial cell function.,While the pathogenic role of each of these mitochondrial alterations in the endothelial cells I/R injury remains complex, profiling of mitochondrial oxidative stress and mitochondrial dynamics in endothelial cell dysfunction may offer promising potential targets in the search for novel diagnostics and therapeutics in cardiac microvascular I/R injury.,The objective of this review is to discuss the role of mitochondrial oxidative stress on cardiac microvascular endothelial cells dysfunction.,Mitochondrial dynamics, including mitochondrial fission and fusion, are critically discussed to understand their roles in endothelial cell survival.,Finally, mitophagy, as a degradative mechanism for damaged mitochondria, is summarized to figure out its contribution to the progression of microvascular I/R injury. | Ripk3-required necroptosis and mitochondria-mediated apoptosis are the predominant types of cell death that largely account for the development of cardiac ischemia reperfusion injury (IRI).,Here, we explored the effect of Ripk3 on mitochondrial apoptosis.,Compared with wild-type mice, the infarcted area in Ripk3-deficient (Ripk3-/-) mice had a relatively low abundance of apoptotic cells.,Moreover, the loss of Ripk3 protected the mitochondria against IRI and inhibited caspase9 apoptotic pathways.,These protective effects of Ripk3 deficiency were relied on mitophagy activation.,However, inhibition of mitophagy under Ripk3 deficiency enhanced cardiomyocyte and endothelia apoptosis, augmented infarcted area and induced microvascular dysfunction.,Furthermore, ischemia activated mitophagy by modifying FUNDC1 dephosphorylation, which substantively engulfed mitochondria debris and cytochrome-c, thus blocking apoptosis signal.,However, reperfusion injury elevated the expression of Ripk3 which disrupted FUNDC1 activation and abated mitophagy, increasing the likelihood of apoptosis.,In summary, this study confirms the promotive effect of Ripk3 on mitochondria-mediated apoptosis via inhibition of FUNDC1-dependent mitophagy in cardiac IRI.,These findings provide new insight into the roles of Ripk3-related necroptosis, mitochondria-mediated apoptosis and FUNDC1-required mitophagy in cardiac IRI.,fx1,•Cardiac IR injury augments Ripk3 expression that contributes to cardiac dysfunction and microvascular collapse.,•Ripk3 activates mitochondria-dependent cellular apoptosis which is responsible for the cardiomyocyte and endothelia death.,•In the ischemic phase, FUNDC1-required mitophagy has the ability to block caspase-9 related mitochondrial apoptosis pathways.,•After reperfusion, Ripk3 is upregulated and impairs the FUNDC1-required mitophagy, leading to cellular apoptosis.,Cardiac IR injury augments Ripk3 expression that contributes to cardiac dysfunction and microvascular collapse.,Ripk3 activates mitochondria-dependent cellular apoptosis which is responsible for the cardiomyocyte and endothelia death.,In the ischemic phase, FUNDC1-required mitophagy has the ability to block caspase-9 related mitochondrial apoptosis pathways.,After reperfusion, Ripk3 is upregulated and impairs the FUNDC1-required mitophagy, leading to cellular apoptosis. | 1 |
A higher risk of thrombosis has been described as a prominent feature of coronavirus disease 2019 (COVID-19).,This systematic review synthesizes current data on thrombosis risk, prognostic implications, and anticoagulation effects in COVID-19.,We included 37 studies from 4070 unique citations.,Meta-analysis was performed when feasible.,Coagulopathy and thrombotic events were frequent among patients with COVID-19 and further increased in those with more severe forms of the disease.,We also present guidance on the prevention and management of thrombosis from a multidisciplinary panel of specialists from Mayo Clinic.,The current certainty of evidence is generally very low and continues to evolve. | Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected.,Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases.,Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders.,Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19.,This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed.,With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions. | 1 |
Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome.,Assess the effect of ACEI/ARBs on outcome in COVID-19 patients.,Hospital-based prospective study.,A total of 431 patients consecutively presenting at the Emergency Department and found to be affected by COVID-19 were assessed.,Relevant clinical and laboratory variables were recorded, focusing on the type of current anti hypertensive treatment.,Outcome variables were NO, MILD, SEVERE respiratory distress (RD) operationally defined and DEATH.,Hypertension was the single most frequent comorbidity (221/431 = 51%).,Distribution of antihypertensive treatment was: ACEIs 77/221 (35%), ARBs 63/221 (28%), OTHER than ACEIs or ARBs 64/221 (29%).,In 17/221 (8%) antihypertensive medication was unknown.,The proportion of patients taking ACEIs, ARBs or OTHERs who developed MILD or SEVERE RD was 43/77 (56%), 33/53 (52%), 39/64 (61%) and 19/77 (25%), 16/63 (25%) and 16/64 (25%), respectively, with no statistical difference between groups.,Despite producing a RR for SEVERE RD of 2.59 (95% CI 1.93-3.49), hypertension was no longer significant in a logistic regression analysis that identified age, CRP and creatinine as the sole independent predictors of SEVERE RD and DEATH.,ACEIs and ARBs do not promote a more severe outcome of COVID-19.,There is no reason why they should be withheld in affected patients. | Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | 1 |
We aimed to compare the outcome of acute ischemic stroke (AIS) patients who received endovascular thrombectomy (EVT) with confirmed COVID-19 to those without.,We performed a retrospective analysis using the Vizient Clinical Data Base and included hospital discharges from April 1 to July 31 2020 with ICD-10 codes for AIS and EVT.,The primary outcome was in-hospital death and the secondary outcome was favorable discharge, defined as discharge home or to acute rehabilitation.,We compared patients with laboratory-confirmed COVID-19 to those without.,As a sensitivity analysis, we compared COVID-19 AIS patients who did not undergo EVT to those who did, to balance potential adverse events inherent to COVID-19 infection.,We identified 3165 AIS patients who received EVT during April to July 2020, in which COVID-19 was confirmed in 104 (3.3%).,Comorbid COVID-19 infection was associated with younger age, male sex, diabetes, black race, Hispanic ethnicity, intubation, acute coronary syndrome, acute renal failure, and longer hospital and intensive care unit length of stay.,The rate of in-hospital death was 12.4% without COVID-19 vs 29.8% with COVID-19 (P<0.001).,In mixed-effects logistic regression that accounted for patient clustering by hospital, comorbid COVID-19 increased the odds of in-hospital death over four-fold (OR 4.48, 95% CI 3.02 to 6.165).,Comorbid COVID-19 was also associated with lower odds of a favorable discharge (OR 0.43, 95% CI 0.30 to 0.61).,In the sensitivity analysis, comparing AIS patients with COVID-19 who did not undergo EVT (n=2139) to the AIS EVT patients with COVID-19, there was no difference in the rate of in-hospital death (30.6% vs 29.8%, P=0.868), and AIS EVT patients had a higher rate of favorable discharge (32.4% vs 47.1%, P=0.002).,In AIS patients treated with EVT, comorbid COVID-19 infection was associated with in-hospital death and a lower odds of favorable discharge compared with patients without COVID-19, but not compared with AIS patients with COVID-19 who did not undergo EVT.,AIS EVT patients with COVID-19 were younger, more likely to be male, have systemic complications, and almost twice as likely to be black and over three times as likely to be Hispanic. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health.,Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases.,Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes.,Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein.,In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19.,We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction.,Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells.,Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process. | An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as a global pandemic.,SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality.,It is unclear whether cardiac injury is caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation.,Here, we investigate whether cardiomyocytes are permissive for SARS-CoV-2 infection.,Two strains of SARS-CoV-2 infected human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) as demonstrated by detection of intracellular double-stranded viral RNA and viral spike glycoprotein expression.,Increasing concentrations of viral RNA are detected in supernatants of infected cardiomyocytes, which induced infections in Caco-2 cell lines, documenting productive infections.,SARS-COV-2 infection and induced cytotoxic and proapoptotic effects associated with it abolished cardiomyocyte beating.,RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signalling, apoptosis, and reactive oxygen stress.,SARS-CoV-2 infection and cardiotoxicity was confirmed in a 3D cardiosphere tissue model.,Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2.,Coronavirus particles were further observed in cardiomyocytes of a patient with COVID-19.,Infection of iPS-CMs was dependent on cathepsins and angiotensin-converting enzyme 2 (ACE2), and was blocked by remdesivir.,This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an ACE2- and cathepsin-dependent manner.,SARS-CoV-2 infection of cardiomyocytes is inhibited by the antiviral drug remdesivir.,Although this study cannot address whether cardiac injury and dysfunction in COVID-19 patients is caused by direct infection of cardiomyocytes, the demonstration of direct cardiotoxicity in cardiomyocytes, organ mimics, human heart slices and human hearts warrants the further monitoring of cardiotoxic effects in COVID-19 patients.,Graphical Abstract | This study evaluated cardiac involvement in patients recovered from coronavirus disease-2019 (COVID-19) using cardiac magnetic resonance (CMR).,Myocardial injury caused by COVID-19 was previously reported in hospitalized patients.,It is unknown if there is sustained cardiac involvement after patients’ recovery from COVID-19.,Twenty-six patients recovered from COVID-19 who reported cardiac symptoms and underwent CMR examinations were retrospectively included.,CMR protocols consisted of conventional sequences (cine, T2-weighted imaging, and late gadolinium enhancement [LGE]) and quantitative mapping sequences (T1, T2, and extracellular volume [ECV] mapping).,Edema ratio and LGE were assessed in post-COVID-19 patients.,Cardiac function, native T1/T2, and ECV were quantitatively evaluated and compared with controls.,Fifteen patients (58%) had abnormal CMR findings on conventional CMR sequences: myocardial edema was found in 14 (54%) patients and LGE was found in 8 (31%) patients.,Decreased right ventricle functional parameters including ejection fraction, cardiac index, and stroke volume/body surface area were found in patients with positive conventional CMR findings.,Using quantitative mapping, global native T1, T2, and ECV were all found to be significantly elevated in patients with positive conventional CMR findings, compared with patients without positive findings and controls (median [interquartile range]: native T1 1,271 ms [1,243 to 1,298 ms] vs. 1,237 ms [1,216 to 1,262 ms] vs. 1,224 ms [1,217 to 1,245 ms]; mean ± SD: T2 42.7 ± 3.1 ms vs.,38.1 ms ± 2.4 vs.,39.1 ms ± 3.1; median [interquartile range]: 28.2% [24.8% to 36.2%] vs.,24.8% [23.1% to 25.4%] vs.,23.7% [22.2% to 25.2%]; p = 0.002; p < 0.001, and p = 0.002, respectively).,Cardiac involvement was found in a proportion of patients recovered from COVID-19.,CMR manifestation included myocardial edema, fibrosis, and impaired right ventricle function.,Attention should be paid to the possible myocardial involvement in patients recovered from COVID-19 with cardiac symptoms. | 1 |
Little is known about the arterial complications and hypercoagulability associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.,We sought to characterize our experience with arterial thromboembolic complications in patients with hospitalized for coronavirus disease 2019 (COVID-19).,All patients admitted from March 1 to April 20, 2020, and who underwent carotid, upper, lower and aortoiliac arterial duplex, computed tomography angiogram or magnetic resonance angiography for suspected arterial thrombosis were included.,A retrospective case control study design was used to identify, characterize and evaluate potential risk factors for arterial thromboembolic disease in SARS-CoV-2 positive patients.,Demographics, characteristics, and laboratory values were abstracted and analyzed.,During the study period, 424 patients underwent 499 arterial duplex, computed tomography angiogram, or magnetic resonance angiography imaging studies with an overall 9.4% positive rate for arterial thromboembolism.,Of the 40 patients with arterial thromboembolism, 25 (62.5%) were SARS-CoV-2 negative or admitted for unrelated reasons and 15 (37.5%) were SARS-CoV-2 positive.,The odds ratio for arterial thrombosis in COVID-19 was 3.37 (95% confidence interval, 1.68-6.78; P = .001).,Although not statistically significant, in patients with arterial thromboembolism, patients who were SARS-CoV-2 positive compared with those testing negative or not tested tended to be male (66.7% vs 40.0%; P = .191), have a less frequent history of former or active smoking (42.9% vs 68.0%; P = .233) and have a higher white blood cell count (14.5 vs 9.9; P = .208).,Although the SARS-CoV-2 positive patients trended toward a higher the neutrophil-to-lymphocyte ratio (8.9 vs 4.1; P = .134), creatinine phosphokinase level (359.0 vs 144.5; P = .667), C-reactive protein level (24.2 vs 13.8; P = .627), lactate dehydrogenase level (576.5 vs 338.0; P = .313), and ferritin level (974.0 vs 412.0; P = .47), these differences did not reach statistical significance.,Patients with arterial thromboembolic complications and SARS-CoV-2 positive when compared with SARS-CoV-2 negative or admitted for unrelated reasons were younger (64 vs 70 years; P = .027), had a significantly higher body mass index (32.6 vs 25.5; P = .012), a higher d-dimer at the time of imaging (17.3 vs 1.8; P = .038), a higher average in hospital d-dimer (8.5 vs 2.0; P = .038), a greater distribution of patients with clot in the aortoiliac location (5 vs 1; P = .040), less prior use of any antiplatelet medication (21.4% vs 62.5%; P = .035), and a higher mortality rate (40.0% vs 8.0%; P = .041).,Treatment of arterial thromboembolic disease in COVID-19 positive patients included open thromboembolectomy in six patients (40%), anticoagulation alone in four (26.7%), and five (33.3%) did not require or their overall illness severity precluded additional treatment.,Patients with SARS-CoV-2 are at risk for acute arterial thromboembolic complications despite a lack of conventional risk factors.,A hyperinflammatory state may be responsible for this phenomenon with a preponderance for aortoiliac involvement.,These findings provide an early characterization of arterial thromboembolic disease in SARS-CoV-2 patients. | Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | 1 |
During the COVID-19 pandemic, excess mortality has been reported, while hospitalisations for acute cardiovascular events reduced.,Brazil is the second country with more deaths due to COVID-19.,We aimed to evaluate excess cardiovascular mortality during COVID-19 pandemic in 6 Brazilian capital cities.,Using the Civil Registry public database, we evaluated total and cardiovascular excess deaths, further stratified in specified cardiovascular deaths (acute coronary syndromes and stroke) and unspecified cardiovascular deaths in the 6 Brazilian cities with greater number of COVID-19 deaths (São Paulo, Rio de Janeiro, Fortaleza, Recife, Belém, Manaus).,We compared observed with expected deaths from epidemiological weeks 12-22 of 2020.,We also compared the number of hospital and home deaths during the period.,There were 65 449 deaths and 17 877 COVID-19 deaths in the studied period and cities for 2020.,Cardiovascular mortality increased in most cities, with greater magnitude in the Northern capitals.,However, while there was a reduction in specified cardiovascular deaths in the most cities, the Northern capitals showed an increase of these events.,For unspecified cardiovascular deaths, there was a marked increase in all cities, which strongly correlated to the rise in home deaths (r=0.86, p=0.01).,Excess cardiovascular mortality was greater in the less developed cities, possibly associated with healthcare collapse.,Specified cardiovascular deaths decreased in the most developed cities, in parallel with an increase in unspecified cardiovascular and home deaths, presumably as a result of misdiagnosis.,Conversely, specified cardiovascular deaths increased in cities with a healthcare collapse. | Although patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk patient segment.,This study sought to examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care health system.,Acute cardiovascular hospitalizations were tracked between January 1, 2019, and March 31, 2020.,Daily hospitalization rates were estimated using negative binomial models.,Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference.,From January 1, 2019, to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons.,There were 43.4% (95% confidence interval [CI]: 27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 compared with March 2019 (p < 0.001).,The daily rate of hospitalizations did not change throughout 2019 (-0.01% per day [95% CI: -0.04% to +0.02%]; p = 0.50), January 2020 (-0.5% per day [95% CI: -1.6% to +0.5%]; p = 0.31), or February 2020 (+0.7% per day [95% CI: -0.6% to +2.0%]; p = 0.27).,There was significant daily decline in hospitalizations in March 2020 (-5.9% per day [95% CI: -7.6% to -4.3%]; p < 0.001).,Length of stay was shorter (4.8 days [25th to 75th percentiles: 2.4 to 8.3 days] vs.,6.0 days [25th to 75th percentiles: 3.1 to 9.6 days]; p = 0.003) and in-hospital mortality was not significantly different (6.2% vs.,4.4%; p = 0.30) in March 2020 compared with March 2019.,During the first phase of the COVID-19 pandemic, there was a marked decline in acute cardiovascular hospitalizations, and patients who were admitted had shorter lengths of stay.,These data substantiate concerns that acute care of cardiovascular conditions may be delayed, deferred, or abbreviated during the COVID-19 pandemic. | 1 |
Patients with coronavirus disease 2019 (COVID-19) who are critically ill develop vascular complications characterized by thrombosis of small, medium, and large vessels.,Dysfunction of the vascular endothelium due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been implicated in the pathogenesis of the COVID-19 vasculopathy.,Although initial reports suggested that endothelial injury was caused directly by the virus, recent studies indicate that endothelial cells do not express angiotensin-converting enzyme 2, the receptor that SARS-CoV-2 uses to gain entry into cells, or express it at low levels and are resistant to the infection.,These new findings, together with the observation that COVID-19 triggers a cytokine storm capable of injuring the endothelium and disrupting its antithrombogenic properties, favor an indirect mechanism of endothelial injury mediated locally by an augmented inflammatory reaction to infected nonendothelial cells, such as the bronchial and alveolar epithelium, and systemically by the excessive immune response to infection.,Herein we review the vascular pathology of COVID-19 and critically discuss the potential mechanisms of endothelial injury in this disease. | In December 2019, the world was introduced to a new betacoronavirus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) for its propensity to cause rapidly progressive lung damage, resulting in high death rates.,As fast as the virus spread, it became evident that the novel coronavirus causes a multisystem disease (COVID‐19) that may involve multiple organs and has a high risk of thrombosis associated with striking elevations in pro‐inflammatory cytokines, D‐dimer, and fibrinogen, but without disseminated intravascular coagulation.,Postmortem studies have confirmed the high incidence of venous thromboembolism, but also notably revealed diffuse microvascular thrombi with endothelial swelling, consistent with a thrombotic microangiopathy, and inter‐alveolar endothelial deposits of complement activation fragments.,The clinicopathologic presentation of COVID‐19 thus parallels that of other thrombotic diseases, such as atypical hemolytic uremic syndrome (aHUS), that are caused by dysregulation of the complement system.,This raises the specter that many of the thrombotic complications arising from SARS‐CoV‐2 infections may be triggered and/or exacerbated by excess complement activation.,This is of major potential clinical relevance, as currently available anti‐complement therapies that are highly effective in protecting against thrombosis in aHUS, could be efficacious in COVID‐19.,In this review, we provide mounting evidence for complement participating in the pathophysiology underlying the thrombotic diathesis associated with pathogenic coronaviruses, including SARS‐CoV‐2.,Based on current knowledge of complement, coagulation and the virus, we suggest lines of study to identify novel therapeutic targets and the rationale for clinical trials with currently available anti‐complement agents for COVID‐19. | 1 |
Controversy has arisen in the scientific community on whether the use of renin‐angiotensin system (RAS) inhibitors in the context of COVID‐19 would be beneficial or harmful.,A meta‐analysis of eligible studies comparing the occurrence of severe and fatal COVID‐19 in infected hypertensive patients who were under treatment with angiotensin‐converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted.,PubMed, Google Scholar, the Cochrane Library, medRxiv and bioRxiv were searched for relevant studies.,Fixed‐effects models or random‐effects models were used depending on the heterogeneity between estimates.,A total of eighteen studies with 17 311 patients were included.,The use of RAS inhibitors was associated with a significant 16% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR: 0.84 (95% CI: 0.73‐0.95), P = .007, I2 = 65%.,The results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis of COVID‐19, and could even be protective in hypertensive subjects.,Hypertensive patients should continue these drugs even if they become infected with SARS‐CoV‐2.,Controversy exists on whether RAS inhibitors are beneficial or harmful in COVID‐19.,In this meta‐analysis, the use of RAS inhibitors was not associated with a worse COVID‐19 prognosis and was even protective in hypertensive patients.,Patients should continue these drugs during their COVID‐19 illness. | A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19. | 1 |
The aim of this study was to describe clinical, imaging, and laboratory features of acute pulmonary embolism (APE) in patients with COVID-19 associated pneumonia.,Patients with COVID-19 associated pneumonia who underwent a computed tomography pulmonary artery (CTPA) scan for suspected APE were retrospectively studied.,Laboratory data and CTPA images were collected.,Imaging characteristics were analyzed descriptively.,Laboratory data were analyzed and compared between patients with and without APE.,A series of 25 COVID-19 patients who underwent CTPA between January 2020 and February 2020 were enrolled.,The median D-dimer level founded in these 25 patients was 6.06 μg/mL (interquartile range [IQR] 1.90-14.31 μg/mL).,Ten (40%) patients with APE had a significantly higher level of D-dimer (median, 11.07 μg/mL; IQR, 7.12-21.66 vs median, 2.44 μg/mL; IQR, 1.68-8.34, respectively, P = .003), compared with the 15 (60%) patients without APE.,No significant differences in other laboratory data were found between patients with and without APE.,Among the 10 patients with APE, 6 (60%) had a bilateral pulmonary embolism, while 4 had a unilateral embolism.,The thrombus-prone sites were the right lower lobe (70%), the left upper lobe (60%), both upper lobe (40%) and the right middle lobe (20%).,The thrombus was partially or completely absorbed after anticoagulant therapy in 3 patients who underwent a follow-up CTPA.,Patients with COVID-19 associated pneumonia have a risk of developing APE during the disease.,When the D-dimer level abnormally increases in patients with COVID-19 pneumonia, CTPA should be performed to detect and assess the severity of APE. | Unlabelled Image,•Venous thromboembolism (VTE) is a frequent complication in COVID-19 patients.,•Single-center study of COVID-19 patients admitted to general ward.,•17.0% of patients with VTE•Lack of thromboprophylaxis and leukocytosis were independent risk factors of VTE.,•VTE is independently associated with worse in-hospital outcomes.,Venous thromboembolism (VTE) is a frequent complication in COVID-19 patients.,Single-center study of COVID-19 patients admitted to general ward.,17.0% of patients with VTE,Lack of thromboprophylaxis and leukocytosis were independent risk factors of VTE.,VTE is independently associated with worse in-hospital outcomes. | 1 |
This cohort study assess the association of receipt of medication for opioid use disorder and mortality after hospitalization for injection drug use-associated infective endocarditis in Massachusetts.,Is there an association between receipt of medication for opioid use disorder (MOUD) and mortality after hospitalization for injection drug use-associated infective endocarditis?,In this cohort study 679 individuals hospitalized with injection drug use-associated endocarditis, 24% received MOUD within 3 months of discharge.,MOUD receipt within 3 months of discharge was not associated with reduced mortality but was associated with a reduction in mortality in the month received.,In this study, treatment with MOUD was uncommon and was associated with reduced mortality in the time-varying analysis but not the main analysis, possibly owing to poor treatment retention.,Although hospitalizations for injection drug use-associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown.,To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality.,This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE-related discharges between July 1, 2011, and June, 30, 2015, were analyzed.,All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge.,Data were analyzed from November 11, 2018, to June 23, 2020.,Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE.,The main outcome was all-cause mortality.,The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated.,Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness.,In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure.,Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness.,A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge.,Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine.,The crude mortality rate was 9.2 deaths per 100 person-years.,MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89).,In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use-associated endocarditis only in the month it was received.,Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial. | The rising incidence of infective endocarditis (IE) among people who inject drugs (PWID) has been a major concern across North America.,The coincident rise in IE and change of drug preference to hydromorphone controlled-release (CR) among our PWID population in London, Ontario intrigued us to study the details of injection practices leading to IE, which have not been well characterized in literature.,A case-control study, using one-on-one interviews to understand risk factors and injection practices associated with IE among PWID was conducted.,Eligible participants included those who had injected drugs within the last 3 months, were > 18 years old and either never had or were currently admitted for an IE episode.,Cases were recruited from the tertiary care centers and controls without IE were recruited from outpatient clinics and addiction clinics in London, Ontario.,Thirty three cases (PWID IE+) and 102 controls (PWID but IE-) were interviewed.,Multivariable logistic regressions showed that the odds of having IE were 4.65 times higher among females (95% CI 1.85, 12.28; p = 0.001) and 5.76 times higher among PWID who did not use clean injection equipment from the provincial distribution networks (95% CI 2.37, 14.91; p < 0.001).,Injecting into multiple sites and heating hydromorphone-CR prior to injection were not found to be significantly associated with IE.,Hydromorphone-CR was the most commonly injected drug in both groups (90.9% cases; 81.4% controls; p = 0.197).,Our study highlights the importance of distributing clean injection materials for IE prevention.,Furthermore, our study showcases that females are at higher risk of IE, which is contrary to the reported literature.,Gender differences in injection techniques, which may place women at higher risk of IE, require further study.,We suspect that the very high prevalence of hydromorphone-CR use made our sample size too small to identify a significant association between its use and IE, which has been established in the literature. | 1 |
While pulmonary embolism (PE) appears to be a major issue in COVID-19, data remain sparse.,We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of COVID-19 patients.,In a retrospective multicentre observational study, we included consecutive patients hospitalized for COVID-19.,Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit (ICU) were excluded.,Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA.,The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both P < 0.001).,In an univariable analysis, traditional venous thrombo-embolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic dose anticoagulation before hospitalization or prophylactic dose anticoagulation introduced during hospitalization had lower PE occurrence [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.14-0.91, P = 0.04; and OR 0.11, 95% CI 0.06-0.18, P < 0.001, respectively].,In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95% CI 1.003-1.069, P = 0.04), anticoagulation with a prophylactic dose (OR 0.83, 95% CI 0.79-0.85, P < 0.001) or a therapeutic dose (OR 0.87, 95% CI 0.82-0.92, P < 0.001), C-reactive protein (OR 1.03, 95% CI 1.01-1.04, P = 0.001), and time from symptom onset to hospitalization (OR 1.02, 95% CI 1.006-1.038, P = 0.002).,PE risk factors in the COVID-19 context do not include traditional thrombo-embolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.,Graphical Abstract | Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival. | 1 |
COVID-19 has rapidly impacted on mortality worldwide.1 There is unprecedented urgency to understand who is most at risk of severe outcomes, requiring new approaches for timely analysis of large datasets.,Working on behalf of NHS England we created OpenSAFELY: a secure health analytics platform covering 40% of all patients in England, holding patient data within the existing data centre of a major primary care electronic health records vendor.,Primary care records of 17,278,392 adults were pseudonymously linked to 10,926 COVID-19 related deaths.,COVID-19 related death was associated with: being male (hazard ratio 1.59, 95%CI 1.53-1.65); older age and deprivation (both with a strong gradient); diabetes; severe asthma; and various other medical conditions.,Compared to people with white ethnicity, black and South Asian people were at higher risk even after adjustment for other factors (HR 1.48, 1.29-1.69 and 1.45, 1.32-1.58 respectively).,We have quantified a range of clinical risk factors for COVID-19 related death in the largest cohort study conducted by any country to date.,OpenSAFELY is rapidly adding further patients’ records; we will update and extend results regularly. | Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense.,Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported.,SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated.,Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed.,EMB analysis included histology, immunohistochemistry, and detection of SARS‐CoV‐2 genomes by real‐time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany.,Among 104 EMBs investigated, five were confirmed with SARS‐CoV‐2 infected by reverse real‐time transcriptase polymerase chain reaction.,We describe patients of different history of symptoms and time duration.,Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage.,This is the first report that established the evidence of SARS‐CoV‐2 genomes detection in EMBs.,In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases.,EMB‐based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS‐CoV‐2‐infection and to design future specific and personalized treatment strategies. | 1 |
Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival. | The novel coronavirus, SARS-CoV-2, is causing a global pandemic of life-threatening multiorgan disease, called COVID-19.,Accumulating evidence indicates that patients with COVID-19 are at significant risk of thromboembolic complications, mainly affecting the venous, but also the arterial vascular system.,While the risk of venous thromboembolism (VTE) appears to be higher in patients requiring intensive care unit support compared to those admitted to general wards, recent autopsy findings and data on the timing of VTE diagnosis relative to hospitalization clearly suggest that thromboembolic events also contribute to morbidity and mortality in the ambulatory setting.,In addition to a severe hypercoagulable state caused by systemic inflammation and viral endotheliitis, some patients with advanced COVID-19 may develop a coagulopathy, which meets established laboratory criteria for disseminated intravascular coagulation, but is not typically associated with relevant bleeding.,Similar to other medical societies, the Society of Thrombosis and Haemostasis Research has issued empirical recommendations on initiation, dosing, and duration of pharmacological VTE prophylaxis in COVID-19 patients. | 1 |
The vascular endothelium provides the crucial interface between the blood compartment and tissues, and displays a series of remarkable properties that normally maintain homeostasis.,This tightly regulated palette of functions includes control of haemostasis, fibrinolysis, vasomotion, inflammation, oxidative stress, vascular permeability, and structure.,While these functions participate in the moment-to-moment regulation of the circulation and coordinate many host defence mechanisms, they can also contribute to disease when their usually homeostatic and defensive functions over-reach and turn against the host.,SARS-CoV-2, the aetiological agent of COVID-19, causes the current pandemic.,It produces protean manifestations ranging from head to toe, wreaking seemingly indiscriminate havoc on multiple organ systems including the lungs, heart, brain, kidney, and vasculature.,This essay explores the hypothesis that COVID-19, particularly in the later complicated stages, represents an endothelial disease.,Cytokines, protein pro-inflammatory mediators, serve as key danger signals that shift endothelial functions from the homeostatic into the defensive mode.,The endgame of COVID-19 usually involves a cytokine storm, a phlogistic phenomenon fed by well-understood positive feedback loops that govern cytokine production and overwhelm counter-regulatory mechanisms.,The concept of COVID-19 as an endothelial disease provides a unifying pathophysiological picture of this raging infection, and also provides a framework for a rational treatment strategy at a time when we possess an indeed modest evidence base to guide our therapeutic attempts to confront this novel pandemic. | Is psychological, social, and economic stress associated with coronavirus disease 2019 (COVID-19) associated with the incidence of stress cardiomyopathy?,This cohort study included 1914 patients with acute coronary syndrome to compare patients presenting during the COVID-19 pandemic with patients presenting across 4 timelines prior to the pandemic and found a significantly increased incidence of 7.8% of stress cardiomyopathy during the COVID-19 pandemic, compared with prepandemic incidences that ranged from 1.5% to 1.8%.,These findings suggest that psychological, social, and economic stress related to the COVID-19 pandemic was associated with an increased incidence of stress cardiomyopathy.,This cohort study compares the incidence of stress cardiomyopathy among patients presenting with acute coronary syndrome at 2 Ohio hospitals during the coronavirus disease 2019 pandemic vs prepandemic time points.,The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe psychological, social, and economic stress in people’s lives.,It is not known whether the stress of the pandemic is associated with an increase in the incidence of stress cardiomyopathy.,To determine the incidence and outcomes of stress cardiomyopathy during the COVID-19 pandemic compared with before the pandemic.,This retrospective cohort study at cardiac catheterization laboratories with primary percutaneous coronary intervention capability at 2 hospitals in the Cleveland Clinic health system in Northeast Ohio examined the incidence of stress cardiomyopathy (also known as Takotsubo syndrome) in patients presenting with acute coronary syndrome who underwent coronary arteriography.,Patients presenting during the COVID-19 pandemic, between March 1 and April 30, 2020, were compared with 4 control groups of patients with acute coronary syndrome presenting prior to the pandemic across 4 distinct timelines: March to April 2018, January to February 2019, March to April 2019, and January to February 2020.,Data were analyzed in May 2020.,Patients were divided into 5 groups based on the date of their clinical presentation in relation to the COVID-19 pandemic.,Incidence of stress cardiomyopathy.,Among 1914 patient presenting with acute coronary syndrome, 1656 patients (median [interquartile range] age, 67 [59-74]; 1094 [66.1%] men) presented during the pre-COVID-19 period (390 patients in March-April 2018, 309 patients in January-February 2019, 679 patients in March-April 2019, and 278 patients in January-February 2020), and 258 patients (median [interquartile range] age, 67 [57-75]; 175 [67.8%] men) presented during the COVID-19 pandemic period (ie, March-April 2020).,There was a significant increase in the incidence of stress cardiomyopathy during the COVID-19 period, with a total of 20 patients with stress cardiomyopathy (incidence proportion, 7.8%), compared with prepandemic timelines, which ranged from 5 to 12 patients with stress cardiomyopathy (incidence proportion range, 1.5%-1.8%).,The rate ratio comparing the COVID-19 pandemic period to the combined prepandemic period was 4.58 (95% CI, 4.11-5.11; P < .001).,All patients during the COVID-19 pandemic had negative reverse transcription-polymerase chain reaction test results for COVID-19.,Patients with stress cardiomyopathy during the COVID-19 pandemic had a longer median (interquartile range) hospital length of stay compared with those hospitalized in the prepandemic period (COVID-19 period: 8 [6-9] days; March-April 2018: 4 [3-4] days; January-February 2019: 5 [3-6] days; March-April 2019: 4 [4-8] days; January-February: 5 [4-5] days; P = .006).,There were no significant differences between the COVID-19 period and the overall pre-COVID-19 period in mortality (1 patient [5.0%] vs 1 patient [3.6%], respectively; P = .81) or 30-day rehospitalization (4 patients [22.2%] vs 6 patients [21.4%], respectively; P = .90).,This study found that there was a significant increase in the incidence of stress cardiomyopathy during the COVID-19 pandemic when compared with prepandemic periods. | 1 |
The genetic architecture of sporadic congenital heart disease (CHD) is characterized by enrichment in damaging de novo variants in chromatin-modifying genes.,To test the hypothesis that gene pathways contributing to de novo forms of CHD are distinct from those for recessive forms, we analyze 2391 whole-exome trios from the Pediatric Cardiac Genomics Consortium.,We deploy a permutation-based gene-burden analysis to identify damaging recessive and compound heterozygous genotypes and disease genes, controlling for confounding effects, such as background mutation rate and ancestry.,Cilia-related genes are significantly enriched for damaging rare recessive genotypes, but comparatively depleted for de novo variants.,The opposite trend is observed for chromatin-modifying genes.,Other cardiac developmental gene classes have less stratification by mode of inheritance than cilia and chromatin-modifying gene classes.,Our analyses reveal dominant and recessive CHD are associated with distinct gene functions, with cilia-related genes providing a reservoir of rare segregating variation leading to CHD.,Large whole-exome sequencing studies have suggested that the genetic architecture of syndromic congenital heart disease (CHD) is different from sporadic forms.,Here, Watkins et al. estimate the relative contribution of damaging recessive and de novo genotypes to CHD in 2391 trios and find them to be associated with different gene functions. | Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment.,It is increasingly recognized as a highly heritable condition.,The aim of the study was to search for sequence variants that affect the risk of CoA.,We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing.,We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10−22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein.,Approximately 20% of individuals with CoA in Iceland carry this mutation.,We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve.,We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation.,Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA.,This is the first mutation associated with non-familial or sporadic form of CoA at a population level.,The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function. | 1 |
Increases in cardiac troponin indicative of myocardial injury are common in patients with coronavirus disease-2019 (COVID-19) and are associated with adverse outcomes such as arrhythmias and death.,These increases are more likely to occur in those with chronic cardiovascular conditions and in those with severe COVID-19 presentations.,The increased inflammatory, prothrombotic, and procoagulant responses following severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection increase the risk for acute nonischemic myocardial injury and acute myocardial infarction, particularly type 2 myocardial infarction, because of respiratory failure with hypoxia and hemodynamic instability in critically ill patients.,Myocarditis, stress cardiomyopathy, acute heart failure, and direct injury from SARS-CoV-2 are important etiologies, but primary noncardiac conditions, such as pulmonary embolism, critical illness, and sepsis, probably cause more of the myocardial injury.,The structured use of serial cardiac troponin has the potential to facilitate risk stratification, help make decisions about when to use imaging, and inform stage categorization and disease phenotyping among hospitalized COVID-19 patients.,•Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,•Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,•Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification.,Increases in cardiac troponin indicative of myocardial injury are common and prognostic in COVID-19.,Increases can be due to chronic injury, acute nonischemic injury, or acute MI.,Troponin, along with inflammatory and thrombotic markers, may facilitate COVID-19 stage classification and risk stratification. | The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world.,Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system.,In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm.,This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19.,There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19.,Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address.,We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients.,A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications. | 1 |
The COVID-19 pandemic required a significant redeployment of worldwide healthcare resources.,Fear of infection, national lockdowns and altered healthcare priorities have the potential to impact utilisation of healthcare resources for non-communicable diseases.,To survey health professionals’ views of the impact of the COVID-19 pandemic on the rate and timing of admission of patients with ST-elevation myocardial infarction (STEMI), the European Society of Cardiology (ESC) administered an internet-based questionnaire to cardiologists and cardiovascular nurses across 6 continents.,3101 responses were received from 141 countries across 6 continents.,88.3% responded that their country was in “total lockdown” and 7.1% in partial lockdown.,78.8% responded that the number of patients presenting with STEMI was reduced since the coronavirus outbreak and 65.2% indicated that the reduction in STEMI presentations was >40%.,Approximately 60% of all respondents reported that STEMI patients presented later than usual and 58.5% that >40% of STEMI patients admitted to hospital presented beyond the optimal window for primary percutaneous intervention (PCI) or thrombolysis.,Independent predictors of the reported higher rate of delayed STEMI presentation were a country in total lockdown, >100 COVID-19 cases admitted locally, and the complete restructuring of the local cardiology service.,The survey indicates that the impact of COVID-19 on STEMI presentations is likely to be substantial, with both lower presentations and a higher rate of delayed presentations occurring.,This has potentially important ramifications for future healthcare and policy planning in the event of further waves of this pandemic. | The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed. | 1 |
Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement.,Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality.,The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease.,Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death.,Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients.,This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
Individual studies have reported widely variable rates for VTE and bleeding among hospitalized patients with coronavirus disease 2019 (COVID-19).,What is the incidence of VTE and bleeding among hospitalized patients with COVID-19?,In this systematic review and meta-analysis, 15 standard sources and COVID-19-specific sources were searched between January 1, 2020, and July 31, 2020, with no restriction according to language.,Incidence estimates were pooled by using random effects meta-analyses.,Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using the Begg and Egger tests.,The pooled incidence was 17.0% (95% CI, 13.4-20.9) for VTE, 12.1% (95% CI, 8.4-16.4) for DVT, 7.1% (95% CI, 5.3-9.1) for pulmonary embolism (PE), 7.8% (95% CI, 2.6-15.3) for bleeding, and 3.9% (95% CI, 1.2-7.9) for major bleeding.,In subgroup meta-analyses, the incidence of VTE was higher when assessed according to screening (33.1% vs 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs 7.1% in the ward), in prospective studies (25.5% vs 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs.,The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%).,Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT, and subsegmental PE, in critically ill patients and in prospective studies.,Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants and nature of data collection.,Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes.,PROSPERO; No.: CRD42020198864; URL: https://www.crd.york.ac.uk/prospero/. | COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence. | 1 |
Current management of liver ischemia-reperfusion (I/R) injury is mainly based on supportive care and no specific treatment is available.,Irisin, a recently identified hormone, plays pivotal roles in energy expenditure and oxidative metabolism; however, it remains unknown whether irisin has any protective effects on hepatic I/R injury.,In this study, we found that serum and liver irisin levels were markedly decreased at 24 h after hepatic I/R.,Treatment with exogenous irisin improved liver function, reduced liver necrosis and cell apoptosis, and relieved inflammatory response after hepatic I/R.,Meanwhile, exogenous irisin markedly inhibited mitochondrial fission related protein dynamin related protein 1 (drp-1) and fission 1 (Fis-1) expression in hepatic I/R.,Additionally, treatment with exogenous irisin increased mitochondrial content and increased mitochondrial biogenesis related peroxisome proliferative activated receptor-γ (PPARγ) co-activator 1α (PGC-1α) and mitochondrial transcription factor (TFAM) expression.,Furthermore, irisin decreased oxidative stress by upregulating uncoupling proteins (UCP) 2 expression in hepatic I/R.,The results reveal that treatment with exogenous irisin alleviated hepatic I/R injury by restraining mitochondrial fission, promoting mitochondrial biogenesis and relieving oxidative stress.,Irisin treatment appears to be a novel and promising therapeutic approach for hepatic I/R injury.,fx1,•Irisin protects hepatocytes against ischemia/reperfusion (I/R)-induced injury.,•Irisin inhibits excessive mitochondrial fission after hepatic I/R.,•Irisin promotes mitochondrial biogenesis after hepatic I/R.,•Irisin reduces oxidative stress after hepatic I/R.,Irisin protects hepatocytes against ischemia/reperfusion (I/R)-induced injury.,Irisin inhibits excessive mitochondrial fission after hepatic I/R.,Irisin promotes mitochondrial biogenesis after hepatic I/R.,Irisin reduces oxidative stress after hepatic I/R. | Mitochondria are key regulators of cell fate during disease.,They control cell survival via the production of ATP that fuels cellular processes and, conversely, cell death via the induction of apoptosis through release of pro-apoptotic factors such as cytochrome C.,Therefore, it is essential to have stringent quality control mechanisms to ensure a healthy mitochondrial network.,Quality control mechanisms are largely regulated by mitochondrial dynamics and mitophagy.,The processes of mitochondrial fission (division) and fusion allow for damaged mitochondria to be segregated and facilitate the equilibration of mitochondrial components such as DNA, proteins, and metabolites.,The process of mitophagy are responsible for the degradation and recycling of damaged mitochondria.,These mitochondrial quality control mechanisms have been well studied in chronic and acute pathologies such as Parkinson’s disease, Alzheimer’s disease, stroke, and acute myocardial infarction, but less is known about how these two processes interact and contribute to specific pathophysiologic states.,To date, evidence for the role of mitochondrial quality control in acute and chronic disease is divergent and suggests that mitochondrial quality control processes can serve both survival and death functions depending on the disease state.,This review aims to provide a synopsis of the molecular mechanisms involved in mitochondrial quality control, to summarize our current understanding of the complex role that mitochondrial quality control plays in the progression of acute vs chronic diseases and, finally, to speculate on the possibility that targeted manipulation of mitochondrial quality control mechanisms may be exploited for the rationale design of novel therapeutic interventions. | 1 |
Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations.,An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.,We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine.,For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables.,Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator.,To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons.,The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.,In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons.,Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2).,SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.,In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined.,The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons).,The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection.,(Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.) | Supplemental Digital Content is available in the text.,Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males.,According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age.,In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels.,ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients.,There was no evidence of acute COVID-19 or other viral infections.,In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased.,Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed.,The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women.,Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.,Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown.,COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors.,We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood.,In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs.,This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension. | 1 |
To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States.,Observational cohort study.,Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.,All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.,The main outcome was 30 day mortality.,Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.,Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission.,More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation.,Most deaths (510/622, 82%) occurred during hospital stay.,Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not.,Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81).,Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation.,Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05).,Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality).,Results persisted in several sensitivity analyses.,Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events.,These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission. | Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19. | 1 |
At the end of last year, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an acute respiratory illness epidemic in Wuhan, China [1, 2].,The World Health Organization (WHO) termed this illness coronavirus disease 2019 (COVID-19).,The coronavirus family have been shown to enter cells through binding angiotensin-converting enzyme 2 (ACE-2), found mainly on alveolar epithelium and endothelium.,Activation of endothelial cells is thought to be the primary driver for the increasingly recognised complication of thrombosis.,Pulmonary thrombosis appears to be common in COVID-19 pneumonia and takes two forms, proximal pulmonary emboli and/or distal thrombosis.,The possible mechanisms and clinical implications are discussed.https://bit.ly/372Xdhw | Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients. | 1 |
Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications.,So far information is scarce and rapidly emerging.,We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients.,Additional studies were identified by secondary review and alert services.,Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively.,A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units.,The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined.,Although an increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known.,A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.,•Thrombotic events, venous and arterial are frequent in COVID-19, more so in critically ill patients.,•Valid biomarkers to define risk and prognosis are still lacking.,•Anticoagulant prophylaxis is needed in all patients.,•The role of higher doses of anticoagulants in all patients is unclear.,•There is a need to develop standard clinical definitions, common data elements, and standard reporting criteria.,Thrombotic events, venous and arterial are frequent in COVID-19, more so in critically ill patients.,Valid biomarkers to define risk and prognosis are still lacking.,Anticoagulant prophylaxis is needed in all patients.,The role of higher doses of anticoagulants in all patients is unclear.,There is a need to develop standard clinical definitions, common data elements, and standard reporting criteria. | Patients with COVID-19 have a coagulopathy and high thrombotic risk.,In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients.,Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially).,Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma.,In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients.,Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes. | 1 |
Admission rates for acute decompensated heart failure (HF) declined during the COVID‐19 pandemic.,However, the impact of this reduction on hospital mortality is unknown.,We describe temporal trends in the presentation of patients with acute HF and their in‐hospital outcomes at two referral centres in London during the COVID‐19 pandemic.,A total of 1372 patients hospitalized for HF in two referral centres in South London between 7 January and 14 June 2020 were included in the study and their outcomes compared with those of equivalent patients of the same time period in 2019.,The primary outcome was all‐cause in‐hospital mortality.,The number of HF hospitalizations was significantly reduced during the COVID‐19 pandemic, compared with 2019 (P < 0.001).,Specifically, we observed a temporary reduction in hospitalizations during the COVID‐19 peak, followed by a return to 2019 levels.,Patients admitted during the COVID‐19 pandemic had demographic characteristics similar to those admitted during the equivalent period in 2019.,However, in‐hospital mortality was significantly higher in 2020 than in 2019 (P = 0.015).,Hospitalization in 2020 was independently associated with worse in‐hospital mortality (hazard ratio 2.23, 95% confidence interval 1.34-3.72; P = 0.002).,During the COVID‐19 pandemic there was a reduction in HF hospitalization and a higher rate of in‐hospital mortality.,Hospitalization for HF in 2020 is independently associated with more adverse outcomes.,Further studies are required to investigate the predictors of these adverse outcomes to help inform potential changes to the management of HF patients while some constraints to usual care remain.,Temporal trends in heart failure admission and adjusted Kaplan-Meier curves for in‐hospital mortality during the COVID‐19 pandemic. | The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has important implications for the safety of participants in clinical trials and the research staff caring for them and, consequently, for the trials themselves.,Patients with heart failure may be at greater risk of infection with COVID-19 and the consequences might also be more serious, but they are also at risk of adverse outcomes if their clinical care is compromised.,As physicians and clinical trialists, it is our responsibility to ensure safe and effective care is delivered to trial participants without affecting the integrity of the trial.,The social contract with our patients demands no less.,Many regulatory authorities from different world regions have issued guidance statements regarding the conduct of clinical trials during this COVID-19 crisis.,However, international trials may benefit from expert guidance from a global panel of experts to supplement local advice and regulations, thereby enhancing the safety of participants and the integrity of the trial.,Accordingly, the Heart Failure Association of the European Society of Cardiology on 21 and 22 March 2020 conducted web-based meetings with expert clinical trialists in Europe, North America, South America, Australia, and Asia.,The main objectives of this Expert Position Paper are to highlight the challenges that this pandemic poses for the conduct of clinical trials in heart failure and to offer advice on how they might be overcome, with some practical examples.,While this panel of experts are focused on heart failure clinical trials, these discussions and recommendations may apply to clinical trials in other therapeutic areas. | 1 |
Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death.,Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial.,Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein.,The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-β2GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically.,Epitope specificity of anti-β2GPI antibodies was not reported.,To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β2GPI antibodies.,ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19.,Of them, 16 displayed major thrombotic events.,Anti-β2GPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA.,Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA.,No association between thrombosis and aPL was found.,Reactivity against domain 1 and 4-5 of β2GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β2GPI nor with thrombosis.,aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against β2GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome. | •COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,•Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,•Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low.,COVID-19 pneumonia could be associated with an increased risk of venous thrombosis.,Antiphospholipid antibodies might be involved in thrombosis in COVID-19 patients.,Prevalence of antiphospholipid antibodies in COVID-19 and venous thrombosis was low. | 1 |
Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE).,These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE.,ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest.,The panel included 3 patient representatives.,The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020).,The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients.,The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.,The panel agreed on 2 recommendations.,The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE.,These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation.,They will be updated using a living recommendation approach as new evidence becomes available. | The association of severe coronavirus disease 2019 (COVID-19) with an increased risk of venous thromboembolism (VTE) has resulted in specific guidelines for its prevention and management.,The VTE risk appears highest in those with critical care admission.,The need for postdischarge thromboprophylaxis remains controversial, which is reflected in conflicting expert guideline recommendations.,Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only.,We report postdischarge VTE data from an ongoing quality improvement program incorporating root-cause analysis of hospital-associated VTE (HA-VTE).,Following 1877 hospital discharges associated with COVID-19, 9 episodes of HA-VTE were diagnosed within 42 days, giving a postdischarge rate of 4.8 per 1000 discharges.,Over 2019, following 18 159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges).,The odds ratio for postdischarge HA-VTE associated with COVID-19 compared with 2019 was 1.6 (95% confidence interval, 0.77-3.1).,COVID-19 hospitalization does not appear to increase the risk of postdischarge HA-VTE compared with hospitalization with other acute medical illness.,Given that the risk-benefit ratio of postdischarge thromboprophylaxis remains uncertain, randomized controlled trials to evaluate the role of continuing thromboprophylaxis in COVID-19 patients following hospital discharge are required.,•The rate of symptomatic postdischarge VTE following hospitalization with COVID-19 is low.,The rate of symptomatic postdischarge VTE following hospitalization with COVID-19 is low. | 1 |
Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk. | As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the “off-label” repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which have the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death.,With the possibility that a considerable proportion of the world’s population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment. | 1 |
Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations.,An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.,We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine.,For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables.,Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator.,To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons.,The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.,In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons.,Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2).,SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.,In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined.,The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons).,The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection.,(Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.) | This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury. | 1 |
Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).,Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19.,Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.,Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed.,Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.,Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage.,COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05).,In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001).,Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died.,The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.,As of 24 March 2020, six patients with CVD died (54.5%).,Acute CVD is not uncommon in COVID-19.,Our findings suggest that older patients with risk factors are more likely to develop CVD.,The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak. | Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series.,Larger studies have been limited by both geography and specialty.,Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies.,The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.,During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care.,Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations).,Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available.,Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.,The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020.,Data lock for this report was on April 26, 2020.,During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies.,Median patient age was 71 years (range 23-94; IQR 58-79).,Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis.,The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses.,Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.,To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19.,Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients.,This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.,None. | 1 |
Cardiovascular diseases are the leading cause of mortality worldwide.,It is widely known that non-resolving inflammation results in atherosclerotic conditions, which are responsible for a host of downstream pathologies including thrombosis, myocardial infarction (MI), and neurovascular events.,Macrophages, as part of the innate immune response, are among the most important cell types in every stage of atherosclerosis.,In this review we discuss the principles governing macrophage function in the healthy and infarcted heart.,More specifically, how cardiac macrophages participate in myocardial infarction as well as cardiac repair and remodeling.,The intricate balance between phenotypically heterogeneous populations of macrophages in the heart have profound and highly orchestrated effects during different phases of myocardial infarction.,In the early “inflammatory” stage of MI, resident cardiac macrophages are replaced by classically activated macrophages derived from the bone marrow and spleen.,And while the macrophage population shifts towards an alternatively activated phenotype, the inflammatory response subsides giving way to the “reparative/proliferative” phase.,Lastly, we describe the therapeutic potential of cardiac macrophages in the context of cell-mediated cardio-protection.,Promising results demonstrate innovative concepts; one employing a subset of yolk sac-derived, cardiac macrophages that have complete restorative capacity in the injured myocardium of neonatal mice, and in another example, post-conditioning of cardiac macrophages with cardiosphere-derived cells significantly improved patient’s post-MI diagnoses. | Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury.,In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction.,In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging.,Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation.,These diverse properties are attributed to distinct macrophage subtypes and polarization status.,Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post- MI.,Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification.,This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation. | 1 |
A high prevalence of venous thromboembolism (VTE) has been reported during intensive care unit (ICU) hospitalisation in patients with severe coronavirus disease 2019 (COVID-19) [1, 2].,In most cases, the diagnosis of pulmonary embolism (PE) was incidental as patients underwent computed tomography pulmonary angiography (CTPA) for aggravation of their respiratory condition.,Higher mortality is also described in patients with high D-dimer levels suggesting that VTE complication may contribute to unfavourable prognosis [3, 4].,Even though, prevalence of thromboembolic complications during ICU hospitalisation seems to be high, the prevalence of pulmonary embolism at hospital admission for COVID-19 is unknown and may be underestimated.,There is a high prevalence of pulmonary embolism in patients with COVID-19 at the time of hospital admissionhttps://bit.ly/3reaLjv | Recent studies suggest that thrombotic complications are a common phenomenon in the novel SARS-CoV-2 infection.,The main objective of our study is to assess cumulative incidence of pulmonary embolism (PE) in non critically ill COVID-19 patients and to identify its predicting factors associated to the diagnosis of pulmonary embolism.,We retrospectevely reviewed 452 electronic medical records of patients admitted to Internal Medicine Department of a secondary hospital in Madrid during Covid 19 pandemic outbreak.,We included 91 patients who underwent a multidetector Computed Tomography pulmonary angiography(CTPA) during conventional hospitalization.,The cumulative incidence of PE was assessed ant the clinical, analytical and radiological characteristics were compared between patients with and without PE.,PE incidence was 6.4% (29/452 patients).,Most patients with a confirmed diagnosed with PE recieved low molecular weight heparin (LMWH): 79.3% (23/29).,D-dimer peak was significatly elevated in PE vs non PE patients (14,480 vs 7230 mcg/dL, p = 0.03).,In multivariate analysis of patients who underwent a CTPA we found that plasma D-dimer peak was an independen predictor of PE with a best cut off point of > 5000 µg/dl (OR 3.77; IC95% (1.18-12.16), p = 0.03).,We found ninefold increased risk of PE patients not suffering from dyslipidemia (OR 9.06; IC95% (1.88-43.60).,Predictive value of AUC for ROC is 75.5%.,We found a high incidence of PE in non critically ill hospitalized COVID 19 patients despite standard thromboprophylaxis.,An increase in D-dimer levels is an independent predictor for PE, with a best cut-off point of > 5000 µg/ dl. | 1 |
The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge.,Guidelines have delineated how best to diagnose and manage patients with PE.,However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms.,Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care.,The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis.,The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects.,This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19. | Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients. | 1 |
Receptor-interacting protein 3 (Ripk3)-mediated necroptosis contributes to cardiac ischaemia-reperfusion (IR) injury through poorly defined mechanisms.,Our results demonstrated that Ripk3 was strongly upregulated in murine hearts subjected to IR injury and cardiomyocytes treated with LPS and H2O2.,The higher level of Ripk3 was positively correlated to the infarction area expansion, cardiac dysfunction and augmented cardiomyocytes necroptosis.,Function study further illustrated that upregulated Ripk3 evoked the endoplasmic reticulum (ER) stress, which was accompanied with an increase in intracellular Ca2+ level ([Ca2+]c) and xanthine oxidase (XO) expression.,Activated XO raised cellular reactive oxygen species (ROS) that mediated the mitochondrial permeability transition pore (mPTP) opening and cardiomyocytes necroptosis.,By comparison, genetic ablation of Ripk3 abrogated the ER stress and thus blocked the [Ca2+]c overload-XO-ROS-mPTP pathways, favouring a pro-survival state that ultimately resulted in the inhibition of cardiomyocytes necroptosis in the setting of cardiac IR injury.,In summary, the present study helps to elucidate how necroptosis is mediated by ER stress, via the calcium overload /XO/ROS/mPTP opening axis.,Ripk3 was strongly upregulated in murine hearts subjected to IR injury and cardiomyocytes treated with LPS and H2O2.,The upregulated Ripk3 may evoke the ER stress, which was accompanied with intracellular calcium overload and XO expression.,Activated XO raised cellular reactive oxygen species (ROS) that mediated the mPTP and cardiomyocytes necroptosis.fx1,•ER stress is activated by Ripk3 in cardiac IR injury.,•ER stress induces calcium overload which triggers XO-dependent ROS overproduction.,•ROS outburst promotes mPTP opening that accounts for the necroptosis.,•Inhibiting ER stress favors cardiomyocytes survival and protects cardiac function.,ER stress is activated by Ripk3 in cardiac IR injury.,ER stress induces calcium overload which triggers XO-dependent ROS overproduction.,ROS outburst promotes mPTP opening that accounts for the necroptosis.,Inhibiting ER stress favors cardiomyocytes survival and protects cardiac function. | This study aimed to investigate the role of the intrinsic cardiac nervous system in the mechanism of classical myocardial ischaemic preconditioning (IPC).,Isolated perfused rat hearts were subjected to 35-min regional ischaemia and 60-min reperfusion.,IPC was induced as three cycles of 5-min global ischaemia-reperfusion, and provided significant reduction in infarct size (IS/AAR = 14 ± 2% vs control IS/AAR = 48 ± 3%, p < 0.05).,Treatment with the ganglionic antagonist, hexamethonium (50 μM), blocked IPC protection (IS/AAR = 37 ± 7%, p < 0.05 vs IPC).,Moreover, the muscarinic antagonist, atropine (100 nM), also abrogated IPC-mediated protection (IS/AAR = 40 ± 3%, p < 0.05 vs IPC).,This indicates that intrinsic cardiac ganglia remain intact in the Langendorff preparation and are important in the mechanism of IPC.,In a second group of experiments, coronary effluent collected following IPC, from ex vivo perfused rat hearts, provided significant cardioprotection when perfused through a naïve isolated rat heart prior to induction of regional ischaemia-reperfusion injury (IRI) (IS/ARR = 19 ± 2, p < 0.05 vs control effluent).,This protection was also abrogated by treating the naïve heart with hexamethonium, indicating the humoral trigger of IPC induces protection via an intrinsic neuronal mechanism (IS/AAR = 46 ± 5%, p < 0.05 vs IPC effluent).,In addition, a large release in ACh was observed in coronary effluent was observed following IPC (IPCeff = 0.36 ± 0.03 μM vs C eff = 0.04 ± 0.04 μM, n = 4, p < 0.001).,Interestingly, however, IPC effluent was not able to significantly protect isolated cardiomyocytes from simulated ischaemia-reperfusion injury (cell death = 45 ± 6%, p = 0.09 vs control effluent).,In conclusion, IPC involves activation of the intrinsic cardiac nervous system, leading to release of ACh in the ventricles and induction of protection via activation of muscarinic receptors. | 1 |
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in December 2019 form Wuhan, China leads to coronavirus disease 2019 (COVID-19) pandemic.,While the common cold symptoms are observed in mild cases, COVID-19 is accompanied by multiorgan failure in severe patients.,The involvement of different organs in severe patients results in lengthening the hospitalization duration and increasing the mortality rate.,In this review, we aimed to investigate the involvement of different organs in COVID-19 patients, particularly in severe cases.,Also, we tried to define the potential underlying mechanisms of SARS-CoV2 induced multiorgan failure.,The multi-organ dysfunction is characterized by acute lung failure, acute liver failure, acute kidney injury, cardiovascular disease, and as well as a wide spectrum of hematological abnormalities and neurological disorders.,The most important mechanisms are related to the direct and indirect pathogenic features of SARS-CoV2.,Although the presence of angiotensin-converting enzyme 2, a receptor of SARS-CoV2 in the lung, heart, kidney, testis, liver, lymphocytes, and nervous system was confirmed, there are controversial findings to about the observation of SARS-CoV2 RNA in these organs.,Moreover, the organ failure may be induced by the cytokine storm, a result of increased levels of inflammatory mediators, endothelial dysfunction, coagulation abnormalities, and infiltration of inflammatory cells into the organs.,Therefore, further investigations are needed to detect the exact mechanisms of pathogenesis.,Since the involvement of several organs in COVID-19 patients is important for clinicians, increasing their knowledge may help to improve the outcomes and decrease the rate of mortality and morbidity. | Since the outbreak and rapid spread of COVID-19 starting late December 2019, it has been apparent that disease prognosis has largely been influenced by multiorgan involvement.,Comorbidities such as cardiovascular diseases have been the most common risk factors for severity and mortality.,The hyperinflammatory response of the body, coupled with the plausible direct effects of severe acute respiratory syndrome on body-wide organs via angiotensin-converting enzyme 2, has been associated with complications of the disease.,Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock, and multiorgan failure have precipitated death.,Acknowledging the comorbidities and potential organ injuries throughout the course of COVID-19 is therefore crucial in the clinical management of patients.,This paper aims to add onto the ever-emerging landscape of medical knowledge on COVID-19, encapsulating its multiorgan impact. | 1 |
Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) have a high rate of thrombosis.,We hypothesized that severe acute respiratory syndrome coronavirus 2 infection leads to induction of TF (tissue factor) expression and increased levels of circulating TF-positive extracellular vesicles (EV) that may drive thrombosis.,We measured levels of plasma EV TF activity in 100 patients with COVID-19 with moderate and severe disease and 28 healthy controls.,Levels of EV TF activity were significantly higher in patients with COVID-19 compared with controls.,In addition, levels of EV TF activity were associated with disease severity and mortality.,Finally, levels of EV TF activity correlated with several plasma markers, including D-dimer, which has been shown to be associated with thrombosis in patients with COVID-19.,Our results indicate that severe acute respiratory syndrome coronavirus 2 infection induces the release of TF-positive EVs into the circulation that are likely to contribute to thrombosis in patients with COVID-19.,EV TF activity was also associated with severity and mortality. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries.,This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition.,Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients.,Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly.,This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2.,The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction.,And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition.,The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2. | Supplemental Digital Content is available in the text.,The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function.,Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD.,In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function.,The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging.,Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample.,Among 3254 patients, RD was present in 487 patients (15%).,The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001).,Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function.,Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function.,In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased.,Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm.,URL: https://www.clinicaltrials.gov.,Unique identifier: NCT00470587. | 1 |
Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people.,However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.,We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke.,Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019-September 2020).,The review protocol was previously registered (PROSPERO ID = CRD42020185476).,Data were extracted from articles reporting ≥5 stroke cases in COVID-19.,We complied with the PRISMA guidelines and used the Newcastle-Ottawa Scale to assess data quality.,Data were pooled using a random-effect model.,Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis.,Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9).,The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%).,Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7-22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94-27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34-9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61-6.02), and severe infection (OR = 5.10; 95%CI: 2.72-9.54).,Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3-9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63-4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43-7.90).,Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors.,The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries.,This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition.,Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients.,Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly.,This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2.,The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction.,And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition.,The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2. | •The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen.,•Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death.,•Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications.,•Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function.,•Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment.,•This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.,The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen.,Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death.,Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications.,Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function.,Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment.,This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.,The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a major health crisis, with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) having infected over a million people around the world within a few months of its identification as a human pathogen.,Initially, SARS-CoV-2 infects cells in the respiratory system and causes inflammation and cell death.,Subsequently, the virus spreads out and damages other vital organs and tissues, triggering a complicated spectrum of pathophysiological changes and symptoms, including cardiovascular complications.,Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function.,Diverse clinical manifestations and laboratory abnormalities occur in patients with cardiovascular injury in COVID-19, characterizing the development of this complication, as well as providing clues to diagnosis and treatment.,This review provides a summary of the rapidly appearing laboratory and clinical evidence for the pathophysiology and therapeutic approaches to COVID-19 pulmonary and cardiovascular complications.,Image, graphical abstract | 1 |
Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving. | A potential link between mortality, D-dimer values and a prothrombotic syndrome has been reported in patients with COVID-19 infection.,The National Institute for Public Health of the Netherlands asked a group of Radiology and Vascular Medicine experts to provide guidance for the imaging workup and treatment of these important complications.,This report summarizes evidence for thromboembolic disease, potential diagnostic and preventive actions as well as recommendations for patients with COVID-19 infection. | 1 |
Atrial fibrillation (AF) is the most encountered arrhythmia and has been associated with worse in-hospital outcomes.,This study was to determine the incidence of AF in patients hospitalized with coronavirus disease 2019 (COVID-19) as well as its impact on in-hospital mortality.,Patients hospitalized with a positive COVID-19 polymerase chain reaction test between March 1 and April 27, 2020, were identified from the common medical record system of 13 Northwell Health hospitals.,Natural language processing search algorithms were used to identify and classify AF.,Patients were classified as having AF or not.,AF was further classified as new-onset AF vs history of AF.,AF occurred in 1687 of 9564 patients (17.6%).,Of those, 1109 patients (65.7%) had new-onset AF.,Propensity score matching of 1238 pairs of patients with AF and without AF showed higher in-hospital mortality in the AF group (54.3% vs 37.2%; P < .0001).,Within the AF group, propensity score matching of 500 pairs showed higher in-hospital mortality in patients with new-onset AF as compared with those with a history of AF (55.2% vs 46.8%; P = .009).,The risk ratio of in-hospital mortality for new-onset AF in patients with sinus rhythm was 1.56 (95% confidence interval 1.42-1.71; P < .0001).,The presence of cardiac disease was not associated with a higher risk of in-hospital mortality in patients with AF (P = .1).,In patients hospitalized with COVID-19, 17.6% experienced AF.,AF, particularly new-onset, was an independent predictor of in-hospital mortality. | Association of renin-angiotensin system inhibitors with risk of death in patients with hypertension (HTN) and coronavirus disease 2019 (COVID-19) is not well characterized.,The aim of this study was to evaluate the outcomes of patients with HTN and COVID-19 with respect to different chronic antihypertensive drug intake.,We performed a retrospective, observational study from a large cohort of patients with HTN and with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the Emergency Rooms (ER) of the Piacenza Hospital network from February 21, 2020 to March 20, 2020.,There were 1050 patients admitted to the ERs of the Piacenza Hospital network with COVID-19.,HTN was present in 590 patients [median age, 76.2 years (IQR 68.2-82.6)]; 399 (66.1%) patients were male.,Of them, 248 patients were chronically treated with ACEi, 181 with ARBs, and 161 with other drugs (O-drugs) including beta blockers, diuretics and calcium-channel inhibitors.,With respect to the antihypertensive use, there was no difference between comorbid conditions.,During a follow-up of 38 days (IQR 7.0-46.0), 256 patients (43.4%) died, without any difference stratifying for antihypertensive drugs.,Of them, 107 (43.1%) were in ACEi group vs 67 (37%) in ARBs group vs 82 (50.7%) in O-drugs group, (log-rank test: p = 0.066).,In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality.,After adjusting for potential confounders in risk prediction, the rate of death was similar.,Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19. | 1 |
Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival. | Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic. | 1 |
Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients. | Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | 1 |
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).,This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital.,The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China.,Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection.,Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension.,After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs.,1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013].,Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs.,3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041).,The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs.,3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774).,However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20).,While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19.,However, the results should be considered as exploratory and interpreted cautiously. | To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19. | 1 |
Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed. | There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications. | 1 |
Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs.,The processes that trigger organ damage in COVID-19 are incompletely understood.,Samples were donated from hospitalized patients.,Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.,Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels.,Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage.,In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs.,In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity.,Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage.,These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.,Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung | Patients with COVID-19 have a coagulopathy and high thrombotic risk.,In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients.,Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially).,Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma.,In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients.,Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes. | 1 |
Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role.,Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies.,Critically however, ethnicity has major effects on thrombotic risk, with a 3-4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans.,In this study, we investigated COVID19 coagulopathy in Caucasian patients.,Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity.,Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC).,In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease.,Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC.,Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality. | Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users. | 1 |
Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving. | Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE. | 1 |
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