Hong Kong Med J 2022 Jun;28(3):249–56 | Epub 31 May 2022
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
Cardiovascular complications of COVID-19
YS Archie Lo, MD (UChicago), FACC1; C Jok, BA2; HF Tse, MD, FRCP3,4
1 Faculty of Medicine School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong
2 St Louis University School of Medicine, United States
3 Cardiology Division, Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong
4 Cardiac and Vascular Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, PR China
Corresponding author: Dr YS Archie Lo (email@example.com)
Cardiac injury associated with coronavirus disease 2019 (COVID-19) is associated with high fatality rates. We reviewed the literature on COVID-19-related cardiovascular complications to elucidate the putative causes, diagnosis, and management of cardiovascular complications of COVID-19. Putative causes of these cardiovascular complications include cytokine storm, myocarditis, coronary plaque rupture, hypercoagulability, stress cardiomyopathy or combinations thereof. Cardiac troponin, D-dimer, and N-terminal pro B-type natriuretic peptide levels all provide prognostic information on COVID-19-related cardiovascular complications: elevated levels correlate with poorer prognosis. Coronary thrombosis due to COVID-19 may be associated with a higher thrombus burden than that from other causes. Hypercoagulability can be extremely challenging to treat, and in the absence of contra-indications, thromboprophylaxis is generally indicated in intensive care unit patients. With the exception of percutaneous coronary intervention for acute myocardial infarction, there are no specific treatments for COVID-19-related cardiovascular complications and management is primarily supportive. Whether antiviral therapies, coupled with monoclonal antibodies administered early in the course of COVID-19 illness will prevent severe cardiovascular complications remains to be seen.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a contagious respiratory illness which can cause serious complications including stroke, kidney failure, and cardiovascular complications.1 Cardiovascular complications are a major risk factor for COVID-19 mortality.2 3 4 The aim of this paper was to review the literature, published by December 2020, in order to elucidate the risk factors, putative causes, diagnosis, and management of cardiovascular complications of COVID-19.
Incidence, risk factors and mortality in patients with COVID-19
Two early studies on COVID-19 reported that 20% to 28% of patients with COVID-19 had cardiac injury associated with cardiac dysfunction and arrhythmias.2 3 In a cohort of 416 patients hospitalised with confirmed COVID-19, cardiac injury was reported to occur in 19.7%, and was associated with an unexpectedly high risk of mortality during hospitalisation. Symptoms of COVID-19 were more severe when accompanied by cardiac injury; the mortality rate was higher among patients with cardiac injury than among those without (51.2% vs 4.5%).2
Risk factors: age, sex, and co-morbidities
Independently, in another cohort of 187 patients, those with cardiac injury were more likely to be male, older and to have more co-morbidities including diabetes, hypertension, coronary artery disease, chronic kidney disease, chronic lung disease, etc. Severe COVID-19 infections were also potentially associated with cardiac arrhythmias and the need for mechanical ventilation. The mortality during hospitalisation was 7.62% for patients without underlying cardiovascular disease and normal cardiac troponin (c-TN) levels, but as high as 69.44% for those with underlying cardiovascular disease and elevated c-TN.3
In another report of 72 314 cases (44 672 confirmed) of COVID-19, the crude mortality rate was 2.3%.4 For octogenarians, the case fatality rate was 14.8%. A history of coronary artery disease was present in 4.2% of all cases, but in 22.7% of fatal cases. Case fatality rates were 10.5% for coronary artery disease, 7.3% for diabetes, and 6% for hypertension. Risk of COVID-19 death is highest among the oldest and lowest among the youngest populations. Compared with those aged 18 to 29 years, people aged 75 to 84 years and those aged ≥85 years have 200-times and 630-times, respectively, higher average death rates.5
In a retrospective study of 393 patients, the prevalence of obesity and male sex also appears to be higher in patients with COVID-19 who developed severe symptoms compared with those who did not.6
Putative causes of cardiovascular complications in patients with COVID-19
Cardiovascular complications of COVID-19 are generally associated with poor prognosis. Therefore, prevention and treatment of COVID-19 should be considered a priority. To that end, an understanding of the possible pathogenetic mechanisms resulting in myocardial injury would be helpful. Putative causes of cardiovascular complications in patients with COVID-19 include: cytokine storm, myocarditis, extreme physical and emotional stress, ischaemic injury caused by cardiac microangiopathy or macrovascular coronary artery disease, hypercoagulopathy, right heart strain, and cor pulmonale associated with adult respiratory distress syndrome.
In addition to direct viral damage, uncontrolled inflammation or ‘cytokine storm’—indicated by high levels of inflammatory markers including C-reactive protein (CRP), ferritin, and D-dimer, and increased levels of inflammatory cytokines and chemokines—has been reported in patients with COVID-19.7 8 However, the exact pathogenetic relevance of cytokine storm has yet to be confirmed.9
Myocardial inflammation (myocarditis) is evidenced by elevated c-TN level in some patients10 and autopsy data show mononuclear infiltrate in the myocardium, with related cardiomyocyte necrosis.11 Although there have been case reports of myocarditis in patients with COVID-19, it is unclear whether myocarditis is caused by direct viral invasion or an uncontrolled inflammatory response.10 12
In a cohort study of 39 autopsy cases of COVID-19, cardiac infection with COVID-19 was frequently found; however, overt myocarditis was not observed in the acute phase.13 In contrast, another study reported on the detection of SARS-CoV-2 genomes in endomyocardial biopsies.14
A cardiac magnetic resonance (MR) imaging study of 100 patients recently recovered from COVID-19 reported cardiac involvement in 78% of them, with evidence of ongoing myocardial inflammation in 60% of them. Such involvement appeared independent of pre-existing conditions, severity, overall course of the acute illness, and the time from diagnosis.13 Of 26 competitive athletes, four (15.4%) had cardiac MR findings suggestive of myocarditis and eight additional athletes (30.8%) exhibited late gadolinium enhancement without T2 elevation suggestive of prior myocardial injury.15
In a study of 145 student athletes with COVID-19 who were either asymptomatic or had mild to moderate symptoms during acute infection, cardiac MR findings (at a median of 15 days after a positive test result for COVID-19) were consistent with myocarditis in only two patients (1.4%), based on updated Lake Louise criteria.16
In contrast, preliminary data based on a small autopsy study of 40 patients showed that cardiac injury results more from clotting than from inflammation; microthrombi were frequent, whereas none of the patients had myocarditis.17 While this observation has implications for thromboprophylaxis, whether COVID-19 can cause a viral myocarditis is yet to be confirmed.
Physical and emotional stress
Cases of typical stress cardiomyopathy have also been reported,18 suggesting that both physical and emotional stress may be in part contributory to some cases of cardiovascular complications of COVID-19.
In some patients, ST-segment elevation myocardial infarction (STEMI) may be the first clinical manifestation of COVID-19.19 However, patients with c-TN elevations may not have epicardial coronary artery obstruction at angiography. In a case series of 18 patients with COVID-19 with STEMI, nine patients underwent coronary angiography; six of them (67%) had obstructive disease. A total of 13 patients died in the hospital (4 due to fatal myocardial infarction and 9 due to noncoronary myocardial injury).20 In contrast, patients with COVID-19 with STEMI had more thrombus burden and required more anticoagulation than patients with no COVID-19 infection.21 Very-late stent thrombosis has also been reported with patients with COVID-19 and can be one of the presenting features of COVID-19 in those with a history of coronary stenting.22
Coronavirus disease 2019 is associated with a hypercoagulable state.23 Although the pathogenesis is not completely understood, the following may be observed: elevated fibrinogen and D-dimer; prolongation of both the prothrombin time and activated partial thromboplastin time; and mild thrombocytosis or thrombocytopenia. Major adverse cardiovascular events, and symptomatic thromboembolism, occur frequently in patients with COVID-19, especially among those in the intensive care unit (ICU), even after thromboprophylaxis.24
Unchecked vascular thrombosis may result in neurological complications. In a case series of 214 patients with COVID-19, neurological symptoms were seen in 36.4% of patients and were more common in patients with severe infection.25 A retrospective study of 214 patients reported six patients with acute stroke, of which five were ischaemic stroke.26 Stroke has also been reported in younger patients (aged 33-49 years) with COVID-19.27
Post-mortem studies of 12 patients have reported pulmonary embolism as the direct cause of death in four patients (33%) and deep venous thrombosis in seven patients (58%).28 The risk for venous thromboembolism is markedly elevated with prevalence up to 32%,24 29 30 highest with patients in the ICU.30 In a large study involving 3334 consecutive hospitalised patients with COVID-19, among 829 patients in the ICU, 29.4% had a thrombotic event (13.6% venous and 18.6% arterial).30 Although low-dose anticoagulation has been used for thromboprophylaxis, in a series of 184 critically ill patients with COVID-19, 31% suffered clinically significant thrombotic complications despite low-dose nadroparin.31
A meta-analysis demonstrated thrombocytopenia in patients with severe disease is associated with increased risk of COVID-19 mortality.32 How thrombocytopenia should be factored into the decision to prescribe anticoagulant therapy has yet to be studied.
Cor pulmonale, right heart strain, pulmonary hypertension
An echocardiographic study of 110 COVID-19 cases noted right ventricular dilation in 31% of patients.33 Another study demonstrated that when compared with those in the lowest quartile, patients with the highest right ventricular longitudinal strain quartile had an increased risk of elevated D-dimer and CRP levels, acute cardiac injury, acute respiratory distress syndrome, deep vein thrombosis as well as mortality.34 Acute cor pulmonale, right heart strain, and/or pulmonary hypertension should always be considered in critically ill patients with COVID-19.35
Other significant cardiac issues in COVID-19
Early data suggested an incidence of 16.7% arrhythmias among hospitalised patients with COVID-19 and 44.4% of ICU admissions.36 A multicentre study of 192 patients with COVID-19 reported a prevalence of 12.5% for atrial fibrillation among hospitalised patients with COVID-19.37 Another study evaluating 115 patients with COVID-19 reported atrial tachyarrhythmia in 16.5% of patients, with atrial fibrillation being the most common (63%).38 Those with atrial tachyarrhythmia had higher CRP and D-dimer levels compared with those without atrial tachyarrhythmia. Among 393 patients with COVID-19, atrial arrhythmias were more common among patients on ventilators (18.5% vs 1.9%).6 In another study of 700 patients with COVID-19, nine patients experienced cardiac arrest. All cardiac arrests occurred in patients in the ICU. No patients experienced sustained monomorphic ventricular tachycardia, ventricular fibrillation, or complete heart block. Twenty-five patients had atrial fibrillation, nine had significant bradyarrhythmia, and 10 had non-sustained ventricular tachycardia.39 Among 187 patients with COVID-19, when compared with patients with normal c-TN levels, those with elevated c-TN levels developed more frequent malignant arrhythmias (17.3% vs 1.5%), including ventricular tachycardia/ventricular fibrillation.3
Patients with cardiovascular disease and heart failure are more susceptible to COVID-19 and have a more severe clinical course once infected.40 41 In two studies of patients with COVID-19 hospitalised in Wuhan, heart failure was identified as a complication in about 50% of the fatalities.42 In a retrospective multicentred study, among 8383 patients with heart failure who were hospitalised with COVID-19, nearly one in four died during hospitalisation.43 Evidently, heart failure in patients with COVID-19 may be triggered or aggravated by the acute infection in patients with pre-existing cardiovascular disease or incident acute myocardial insult.
Malignant tachyarrhythmias resulting in cardiac arrest present a dilemma for caregivers. The outcomes of out-of-hospital cardiac arrest were worse during the first weeks of the COVID-19 pandemic in the United States, and this was observed not only in areas with high case-fatality rates but also ones with lower rates.44 In a retrospective study of 136 patients with COVID-19, 119 (87.5%) had a respiratory cause for their cardiac arrest, and the initial rhythm was asystole in 89.7%, pulseless electrical activity in 4.4%, and shockable in 5.9%. The return-of-spontaneous-circulation rate was 13.2% and 30-day survival rate was only 2.9%.45 In another study of 54 patients with COVID-19, the mortality rate following cardiopulmonary resuscitation was even worse (100%). The initial rhythm was non-shockable for 52 patients (96.3%), with pulseless electrical activity being the most common (81.5%). Although the return-of-spontaneous-circulation rate was achieved in 29 patients (53.7%), none survived to be discharged home.46
Prognostic laboratory parameters for cardiovascular complications in patients with COVID-19
Prognostic parameters for cardiovascular complications in patients with COVID-19 include c-TN level, D-dimer level, and N-terminal pro B-type natriuretic peptide (NT-proBNP) level.
Cardiac troponin level
Increases in c-TN level indicative of myocardial injury is common in patients with COVID-19 and is associated with adverse outcomes such as arrhythmias and death. The risk of cardiac injury, as diagnosed by increased c-TN levels (>99th percentile), was found in up to 22% of patients in the ICU, and in 59% of those that died.36 In another study of 2736 patients with COVID-19, c-TN elevation was observed in 36%, and c-TN elevation (>0.09 ng/dL) appears to triple the mortality risk.47 Other studies of patients with COVID-19 have also demonstrated a poorer prognosis, including mortality, in patients with c-TN elevation.41 48 Both c-TN and NT-proBNP levels were documented to be elevated significantly during the course of hospitalisation among those who eventually died, but no dynamic changes were observed among the survivors.3 Moreover, patients with COVID-19 with myocardial injury who also have transthoracic echocardiography abnormalities had a higher mortality risk.49
Elevated D-dimer levels were higher among patients with COVID-19 and was correlated with a poorer prognosis. Multivariate analysis showed increasing odds of in-hospital death associated with D-dimer value above 1 μg/mL.50 In a study of 343 patients with COVID-19, D-dimer levels ≥2.0 μg/mL had a higher incidence of mortality compared with those with D-dimer levels <2.0 μg/mL (12/67 vs 1/267, P<0.001).51 A markedly elevated D-dimer (>6 times the upper limit of normal) is a consistent predictor of thrombotic events and poor overall prognosis.52 Indeed, the International Society on Thrombosis and Haemostasis has advised that for patients who have markedly raised D-dimers (arbitrarily defined as three- to four-fold increase), admission to hospital should be considered even in the absence of other severe symptoms.53 The importance of D-dimer is emphasised in several other international guidelines.52 53 54 55
N-terminal pro B-type natriuretic peptide level
As a biomarker of heart failure, NT-proBNP levels are commonly elevated in hospitalised patients with COVID-19, particularly in those with elevated c-TN levels. The report by Shi et al2 showed that NT-proBNP levels were significantly higher in patients with elevated c-TN levels than in those without c-TN elevation (1689 vs 139 pg/mL). A study of 3219 hospitalised patients with COVID-19, elevated c-TN was detected in 6.5%, and an elevated NT-proBNP level in 12.9%.56 The adjusted hazard ratio for 28-day mortality for c-TN was 7.12 and for NT-proBNP 5.11, confirming that elevated NT-proBNP levels also carry prognostic information. Although NT-proBNP provides corroborating laboratory information on heart failure, the caveat is that NT-proBNP levels increase with age and with various other conditions including renal failure, thus compromising its utility in older patients with confounding variables.
Management of cardiovascular complications of COVID-19
The approach to the diagnosis and management of STEMI in patients with COVID-19 is similar to that for patients without (Table 1). The approaches endorsed by the American College of Cardiology are recommended57: their emphasis is on patient selection for the cardiac catheterisation laboratory, resource allocation, and protection of the interventional team and other healthcare workers involved in caring for the COVID-19 patient.
On occasion, it is reasonable to liberalise the use of intravenous thrombolytic therapy relative to primary percutaneous coronary intervention. Intravenous thrombolytic therapy can be considered for a relatively stable patient with STEMI and COVID-19. Obviously, in those STEMI patients who are critically ill with COVID-19, the decision to reperfuse with either primary percutaneous coronary intervention or intravenous thrombolytic therapy should be individualised, and contingent upon hospital resources. In this regard, the consensus statement from the Taiwan Society of Cardiology is both pragmatic and reasonable.58
In the event that primary percutaneous coronary intervention is to be performed, maximum personal protective equipment is essential. Intubation, suction, and cardiopulmonary resuscitation all result in aerosolisation of respiratory secretions and increase the risks to the hospital staff. Patients already intubated pose less of an infectious risk. Hence patients with COVID-19 or suspected COVID-19 requiring intubation should be intubated prior to arrival to the catheterisation suite.
In the treatment of STEMI patients, an early Hong Kong study reported that both the “symptom onset to first medical contact” and the “door-to-device” times pertaining to primary percutaneous coronary intervention were reported to be substantially prolonged.59
Studies from both England60 and the United States61 have confirmed that hospital admissions for acute coronary syndrome declined by 40% to 48% in the early days of COVID-19. It is likely that patients with acute coronary syndromes avoided attending hospital during this period.
Standard indications for use of various agents for treatment of heart failure apply to patients with COVID-19. The coexistence of heart failure and COVID-19 complicates diagnosis and management because of overlapping chest findings; however, there are notable differences in chest computed tomography between heart failure and COVID-19 pneumonia, such as lesion distribution/morphology, and pulmonary vein engorgement, which can all help to differentiate between the two.62
Cardiopulmonary resuscitation Cardiopulmonary resuscitation poses
Cardiopulmonary resuscitation poses a very high risk for viral spread, and full personal protective equipment should be provided. Immediate intubation should be prioritised in order to minimise the duration of any aerosolisation. While awaiting intubation, bag/mask ventilation with filter is advised.
Several international guidelines have issued recommendations advocating chemoprophylaxis in all hospitalised patients with COVID-19,63 64 65 66 in the absence of both contra-indications and bleeding complications (Table 2). In the event thromboprophylaxis is deemed indicated, low-molecular-weight heparin is preferred, but unfractionated heparin can be used if low-molecular-weight heparin is unavailable or if kidney function is severely impaired. Low-molecular-weight heparin may be preferred over unfractionated heparin for staff safety reasons.
Table 2. Current guideline recommendations for chemoprophylaxis for the prevention of thromboembolism in hospitalised patients with COVID-19 (who do not have suspected or confirmed VTE)
Athletes recovering from COVID-19
As for athletes who have recovered from COVID-19 infections, a recent expert consensus article recommended 2-week convalescence followed by no diagnostic cardiac testing if asymptomatic, and an electrocardiogram and transthoracic echocardiogram in mildly symptomatic athletes with COVID-19 to return to participate in competitive sports.67
Cardiovascular complications of COVID-19 are associated with higher fatality rates. Putative causes of cardiac injury include cytokine storm, myocarditis, extreme physical and emotional stress, ischaemic injury, hypercoagulopathy, right heart strain, and cor pulmonale, or combinations thereof. Echocardiography and c-TN, D-dimer, and NT-proBNP levels all provide prognostic information. Aside from percutaneous coronary intervention for STEMI, there is no specific treatment for COVID-19-associated cardiac injury, and management is primarily supportive. Whether antiviral therapies administered early in the course of disease will prevent severe disease and cardiovascular complications associated with COVID-19 remain to be seen.
Concept or design: YSA Lo.
Acquisition of data: YSA Lo, C Jok.
Analysis or interpretation of data: YSA Lo.
Drafting of the manuscript: YSA Lo.
Critical revision of the manuscript for important intellectual content: YSA Lo, HF Tse.
Acquisition of data: YSA Lo, C Jok.
Analysis or interpretation of data: YSA Lo.
Drafting of the manuscript: YSA Lo.
Critical revision of the manuscript for important intellectual content: YSA Lo, HF Tse.
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
Conflicts of interest
The authors have no conflicts of interest to disclose.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
1. Drake TM, Riad AM, Fairfield CJ, et al. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study. Lancet 2021;398:223-7. Crossref
2. Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol 2020;5:802-10. Crossref
3. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811-8. Crossref
4. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42. Crossref
5. Centers for Disease Control and Prevention, US Department of Health & Human Services. COVID-19 hospitalization and death by age. 11 February 2020 (updated 18 August 2020). Available from: https://www.cdc. gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html. Accessed 2 Dec 2020.
6. Goyal P, Choi JJ, Pinheiro LC, et al. Clinical characteristics of Covid-19 in New York city. N Engl J Med 2020;382:2372-4. Crossref
7. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4. Crossref
8. Zhang X, Tan Y, Ling Y, et al. Viral and host factors related to the clinical outcome of COVID-19. Nature 2020;583;437-40. Crossref
9. Sinha P, Matthay MA, Calfee CS. Is a “Cytokine Storm” relevant to COVID-19? JAMA Intern Med 2020;180:1152-4. Crossref
10. Zeng J, Liu Y, Yuan J, et al. First case of COVID-19 complicated with fulminant myocarditis: a case report and insights. Infection 2020;48:773-7. Crossref
11. Yao XH, Li TY, He ZC, et al. A pathological report of three COVID-19 cases by minimally invasive autopsies [in Chinese]. Zhonghua Bing Li Xue Za Zhi 2020;49:411-7.
12. Lindner D, Fitzek A, Bräuninger H, et al. Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases. JAMA Cardiol 2020;5:1281-5. Crossref
13. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:1265-73. Crossref
14. Escher F, Pietsch H, Aleshcheva G, et al. Detection of viral SARS-CoV-2 genomes and histopathological changes in endomyocardial biopsies. ESC Heart Fail 2020;7:2440-7. Crossref
15. Rajpal S, Tong MS; Borchers J, et al. Cardiovascular magnetic resonance findings in competitive athletes recovering from COVID-19 Infection. JAMA Cardiol 2021;6:116-8. Crossref
16. Starekova J, Bluemke DA, Bradham WS, et al. Evaluation for myocarditis in competitive student athletes recovering from coronavirus disease 2019 with cardiac magnetic resonance imaging. JAMA Cardiol 2021;6:945-50. Crossref
17. Phend C. COVID heart autopsies point more to clot damage than myocarditis. Available from: https://www.medpagetoday.com/meetingcoverage/tct/89143. Accessed 7 Dec 2020.
18. Jabri A, Kalra A, Kumar A, et al. Incidence of stress cardiomyopathy during the coronavirus disease 2019 pandemic. JAMA Netw Open 2020;3:e2014780. Crossref
19. Stefanini GG, Montorfano M, Trabattoni D, et al. ST-elevation myocardial infarction in patients with COVID-19: clinical and angiographic outcomes. Circulation 2020;141:2113-6. Crossref
20. Bangalore S, Sharma A, Slotwiner A, et al. ST-segment elevation in patients with Covid-19—a case series. N Engl J Med 2020;382:2478-80. Crossref
21. Choudry FA, Hamshere SM, Rathod KS, et al. High thrombus burden in patients with COVID-19 presenting with ST-segment elevation myocardial infarction. J Am Coll Cardiol 2020;76:1168-76. Crossref
22. Prieto-Lobato A, Ramos-Martínez R, Vallejo-Calcerrada N, Corbí-Pascual M, Córdoba-Soriano JG. A case series of stent thrombosis during the COVID-19 pandemic. JACC Case Rep 2020;2:1291-6. Crossref
23. Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A. COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia? Lancet 2020;395:1758-9. Crossref
24. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 2020;18:1421-4. Crossref
25. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90. Crossref
26. Li Y, Li M, Wang M, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol 2020;5:279-84. Crossref
27. Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020;382:e60. Crossref
28. Wichmann D, Sperhake JP, Lütgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 2020;173:268-77. Crossref
29. Artifoni M, Danic G, Gautier G, et al. Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors. J Thromb Thrombolysis 2020;50:211-6. Crossref
30. Bilaloglu S, Aphinyanaphongs Y, Jones S, Iturrate E, Hochman J, Berger JS. Thrombosis in hospitalized patients with COVID-19 in a New York City Health System. JAMA 2020;324:799-801. Crossref
31. Klok FA, Kruip MJ, van der Meer NJ, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 2020;191:153-5. Crossref
32. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020;506:145-8. Crossref
33. Argulian E, Sud K, Vogel B, et al. Right ventricular dilation in hospitalized patients with COVID-19 infection. JACC Cardiovasc Imaging 2020;13:2459-61. Crossref
34. Li Y, Li H, Zhu S, et al. Prognostic value of right ventricular longitudinal strain in patients with COVID-19. JACC Cardiovasc Imaging 2020;13:2287-99. Crossref
35. Creel-Bulos C, Hockstein M, Amin N, Melhem S, Truong A, Sharifpour M. Acute cor pulmonale in critically Ill patients with Covid-19. N Engl J Med 2020;382:e70. Crossref
36. Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9. Crossref
37. Russo M, Di Maio M, Attena E, et al. Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: a multicenter observational study. Pharmacol Res 2020;159:104965. Crossref
38. Colon CM, Barrios JG, Chiles JW, et al. Atrial arrhythmias in COVID-19 patients. JACC Clin Electrophysiol 2020;6:1189-90. Crossref
39. Bhatla A, Mayer MM, Adusumalli S, et al. COVID-19 and cardiac arrhythmias. Heart Rhythm 2020;17:1439-44. Crossref
40. Tomasoni D, Italia L, Adamo M, et al. COVID-19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease. Eur J Heart Fail 2020;22:957-66. Crossref
41. Du RH, Liang LR, Yang CQ, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. Eur Respir J 2020;55:2000524. Crossref
42. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020;368:m1091. Crossref
43. Bhatt AS, Jering KS, Vaduganathan M, et al. Clinical outcomes in patients with heart failure hospitalized with COVID-19. JACC Heart Fail 2021;9:65-73. Crossref
44. Chan PS, Girotra S, Tang Y, et al. Outcomes for out-of-hospital cardiac arrest in the United States during the coronavirus disease 2019 pandemic. JAMA Cardiol 2021;6:296-303. Crossref
45. Shao F, Xu S, Ma X, et al. In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China. Resuscitation 2020;151:18-23. Crossref
46. Thapa SB, Kakar TS, Mayer C, Khanal D. Clinical outcomes of in-hospital cardiac arrest in COVID-19. JAMA Intern Med 2021;181:279-81. Crossref
47. Lala A, Johnson KW, Januzzi JL, et al. Prevalence and impact of myocardial injury in patients hospitalized with COVID-19 infection. J Am Coll Cardiol 2020;76:533-46. Crossref
48. Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): evidence from a meta-analysis. Prog Cardiovasc Dis 2020;63:390-1. Crossref
49. Giustino G, Croft LB, Stefanini GG, et al. Characterization of myocardial injury in patients with COVID-19. J Am Coll Cardiol 2020;76:2043-55. Crossref
50. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. Crossref
51. Zhang L, Yan X, Fan Q, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost 2020;18:1324-9. Crossref
52. Spyropoulos AC, Levy JH, Ageno W, et al. Scientific and Standardization Committee communication: clinical guidance on the diagnosis, prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost 2020;18:1859-65. Crossref
53. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID- 19. J Thromb Haemost 2020;18:1023-6. Crossref
54. American Society of Hematology. COVID-19 and VTE/ anticoagulation: frequently asked questions. Available from: https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation. Accessed 23 Jun 2020.
55. Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020;75:2950-73. Crossref
56. Qin JJ, Cheng X, Zhou F, et al. Redefining cardiac biomarkers in predicting mortality of inpatients with COVID-19. Hypertension 2020;76:1104-12. Crossref
57. Mahmud E, Dauerman HL, Welt FG, et al. Management of acute myocardial infarction during the COVID-19 pandemic: a position statement from the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP). J Am Coll Cardiol 2020;76:1375-84. Crossref
58. Li YH, Wang MT, Huang WC, Hwang JJ. Management of acute coronary syndrome in patients with suspected or confirmed coronavirus disease 2019: Consensus from Taiwan Society of Cardiology. J Formos Med Assoc 2021;120:78-82. Crossref
59. Tam CC, Cheung KS, Lam S, et al. Impact of coronavirus disease 2019 (COVID-19) outbreak on ST-segment–elevation myocardial infarction care in Hong Kong, China. Circ Cardiovasc Qual Outcomes 2020;13:e006631. Crossref
60. Mafham MM, Spata E, Goldacre R, et al. COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England. Lancet 2020;396:381-9. Crossref
61. Solomon MD, McNulty EJ, Rana JS, et al. The covid-19 pandemic and the incidence of acute myocardial infarction. N Engl J Med 2020;383:691-3. Crossref
62. Zhu ZW, Tang JJ, Chai XP, et al. Comparison of heart failure and COVID-19 in chest CT features and clinical characteristics. Zhonghua Xin Xue Guan Bing Za Zhi 2020;48:467-71.
63. Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019 CHEST guideline and expert panel report. Chest 2020;158:1143-63. Crossref
64. American Society of Hematology. ASH Guidelines on Use of Anticoagulation in Patients with COVID-19. Available from: https://www.hematology.org/education/clinicians/guidelines-and-quality-care/clinical-practice-guidelines/venous-thromboembolism-guidelines/ash-guidelines-on-use-of-anticoagulation-in-patients-with-covid-19. Accessed 7 Dec 2020.
65. Thachil J, Juffermans NP, Ranucci M, et al. ISTH DIC subcommittee communication on anticoagulation in COVID-19. J Thromb Haemost 2020;18:2138-44. Crossref
66. National Institutes of Health. Antithrombotic therapy in patients with COVID-19. Last updated: 12 May 2020. Available from: https://www.covid19treatmentguidelines. nih.gov/adjunctive-therapy/antithrombotic-therapy/. Accessed 7 Dec 2020.
67. Phelan D, Kim JH, Chung EH. A game plan for the resumption of sport and exercise after coronavirus disease 2019 (COVID-19) infection. JAMA Cardiol 2020;5:1085-6. Crossref