COVID-19 and the heart: direct and indirect impact

Background. The pandemic of severe acute respiratory syndrome COVID-19 drew the attention of researchers and practitioners worldwide to severe cardiovascular injury incurred by the new SARS-CoV-2 coronavirus.

Objectives. A review and structuring of recent evidence on the pathophysiological mechanisms of SARS-CoV-2 impact on cardiovascular system and its major acute complications, assessment of indirect pandemic effects on treatment and diagnosis in practical cardiology.

Methods. Literature sources were mined in the PubMed database with keywords “COVID-19” and “SARS-CoV-2” and the source type “Clinical Trial”, “Meta-Analysis”, “Review”, “Systematic Review”. The search depth was unrestricted, as the vast majority of publications appeared during the past year.

Results. A screening of over 12,000 sources produced 329 most relevant articles available full-text, with 65 included in the review. A key factor of the SARS-CoV-2 penetration into human cell is protein S facilitating the virus—angiotensin-converting enzyme 2 binding and final fusion. Myocardial damage in COVID-19 can occur due to excessive inflammatory response, the disbalance of myocardial oxygen demand and supply, vasculitis, atherosclerotic plaque rupture, coronary spasm, hypoxic vascular damage and endothelial dysfunction, microthrombi formation. The most critical acute cardiovascular complications of COVID-19, apart from myocarditis, are cardiac arrhythmias, acute coronary syndromes, acute heart failure, thrombosis and embolism. The COVID-19 pandemic exerts an indirect negative influence on medical aid in patients with cardiovascular diseases and complications.

Conclusion. Knowledge of the pathophysiological mechanisms of SARS-CoV-2 impact on cardiovascular system and major types of its acute complications allows targeted research into the scenarios of their prevention and treatment. A rational balance is expected between the infection control and treatment for critical noncommunicable, particularly, cardiovascular diseases.

1. Avula A., Nalleballe K., Narula N., Sapozhnikov S., Dandu V., Toom S., Glaser A., Elsayegh D. COVID-19 presenting as stroke. Brain Behav. Immun. 2020; 87: 115-119. DOI: 10.1016/j.bbi.2020.04.077

2. Leisman D.E., Deutschman C.S., Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020; 46(6): 1105-1108. DOI: 10.1007/s00134-020-06059-6

3. Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Muller M.A., Drosten C., Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2): 271-280.e8. DOI: 10.1016/j.cell.2020.02.052

4. Li M.Y., Li L., Zhang Y., Wang X.S. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect. Dis. Poverty. 2020; 9(1): 45. DOI: 10.1186/s40249-020-00662-x

5. Forrester S.J., Booz G.W., Sigmund C.D., Coffman T.M., Kawai T., Rizzo V., Scalia R., Eguchi S. Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology. Physiol. Rev. 2018; 98(3): 1627-1738. DOI: 10.1152/phys-rev.00038.2017

6. Verdecchia P., Cavallini C., Spanevello A., Angeli F. The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur. J. Intern. Med. 2020; 76: 14-20. DOI: 10.1016/j.ejim.2020.04.037

7. South A.M., Diz D.I., Chappell M.C. COVID-19, ACE2, and the cardiovascular consequences. Am. J. Physiol. Heart Circ. Physiol. 2020; 318(5): H1084-H1090. DOI: 10.1152/ajpheart.00217.2020

8. Zhong J., Basu R., Guo D., Chow F.L., Byrns S., Schuster M., Loibner H., Wang X.H., Penninger J.M., Kassiri Z., Oudit G.Y. Angiotensin-converting enzyme 2 suppresses pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction. Circulation. 2010; 122(7): 717-728. DOI: 10.1161/CIRCULATIONA-HA.110.955369

9. Tanwar V., Adelstein J.M., Wold L.E. Double trouble: combined cardiovascular effects of particulate matter exposure and coronavirus disease 2019. Cardiovasc. Res. 2021; 117(1): 85-95. DOI: 10.1093/cvr/cvaa293

10. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H., Cheng Z., Xiong Y., Zhao Y., Li Y., Wang X., Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. J.A.M.A. 2020; 323(11): 1061-1069. DOI: 10.1001/jama.2020.1585

11. Ye Q., Wang B., Mao J. The pathogenesis and treatment of the 'Cytokine Storm’ in COVID-19. J. Infect. 2020; 80(6): 607-613. DOI: 10.1016/j.jinf.2020.03.037

12. Chen G., Wu D., Guo W., Cao Y., Huang D., Wang H., Wang T., Zhang X., Chen H., Yu H., Zhang X., Zhang M., Wu S., Song J., Chen T., Han M., Li S., Luo X., Zhao J., Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 2020; 130(5): 2620-2629. DOI: 10.1172/JCI137244

13. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., Liu S., Zhao P., Liu H., Zhu L., Tai Y., Bai C., Gao T., Song J., Xia P., Dong J., Zhao J., Wang F.S. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020; 8(4): 420-422. DOI: 10.1016/S2213-2600(20)30076-X

14. Mehta P., McAuley D.F., Brown M., Sanchez E., Tat-tersall R.S., Manson J.J.; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229): 1033-1034. DOI: 10.1016/S0140-6736(20)30628-0

15. Siddiqi H.K., Mehra M.R. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J. Heart Lung Transplant. 2020; 39(5): 405-407. DOI: 10.1016/j.healun.2020.03.012

16. Inciardi R.M., Lupi L., Zaccone G, Italia L, Raffo M, Tomasoni D, Cani DS, Cerini M, Farina D, Gavazzi E, Maroldi R, Adamo M, Ammirati E, Sinagra G, Lombardi CM, Metra M. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). J.A.M.A. Cardiol. 2020; 5(7): 819-824. DOI: 10.1001/jamacar-dio.2020.1096

17. Zeng J.H., Liu Y.X., Yuan J., Wang F.X., Wu W.B., Li J.X., Wang L.F., Gao H., Wang Y., Dong C.F., Li Y.J., Xie X.J., Feng C., Liu L. First case of COVID-19 complicated with fulminant myocarditis: a case report and insights. Infection. 2020; 48(5): 773-777. DOI: 10.1007/s15010-020-01424-5

18. Liu K., Fang Y.Y., Deng Y., Liu W., Wang M.F., Ma J.P., Xiao W., Wang Y.N., Zhong M.H., Li C.H., Li G.C., Liu H.G. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin. Med. J. (Engl). 2020; 133(9): 1025-1031. DOI: 10.1097/CM9.0000000000000744

19. Tavazzi G., Pellegrini C., Maurelli M., Belliato M., Sciutti F., Bottazzi A., Sepe P.A., Resasco T., Campo-rotondo R., Bruno R., Baldanti F., Paolucci S., Peleng-hi S., Iotti G.A., Mojoli F., Arbustini E. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur. J. Heart Fail. 2020; 22(5): 911-915. DOI: 10.1002/ejhf.1828

20. Fox S.E., Li G., Akmatbekov A., Harbert J.L., Lameira F.S., Brown J.Q., Vander Heide R.S. Unexpected Features of Cardiac Pathology in COVID-19 Infection. Circulation. 2020; 142(11): 1123-1125. DOI: 10.1161/CIRCULATIONAHA.120.049465

21. Kogan E.A., Berezovskiy Yu.S., Blagova O.V., Kukle-va A.D., Bogacheva G.A., Kurilina E.V., Kalinin D.V., Bagdasaryan T.R., Semeyonova L.A., Gretsov E.M., Ergeshov A.E., Fomin V.V. Miocarditis in Patients with COVID-19 Confirmed by Immunohistochemical. Kardiologiia. 2020; 60(7): 4-10 (In Russ., English abstract). DOI: 10.18087/cardio.2020.7.n1209

22. Mehra M.R., Ruschitzka F.. COVID-19 Illness and Heart Failure: A Missing Link? J.A.C.C. Heart Fail. 2020; 8(6): 512-514. DOI: 10.1016/j.jchf.2020.03.004

23. Cilli A., Cakin O., Aksoy E., Kargin F., Adiguzel N., Karakurt Z., Ergan B., Mersin S., Bozkurt S., Ciftci F., Cengiz M. Acute cardiac events in severe community-acquired pneumonia: A multicenter study. Clin. Respir. J. 2018; 12(7): 2212-2219. DOI: 10.1111/crj.12791

24. Cowan L.T., Lutsey P.L., Pankow J.S., Matsushita K., Ishigami J., Lakshminarayan K. Inpatient and Outpatient Infection as a Trigger of Cardiovascular Disease: The ARIC Study. J. Am. Heart Assoc. 2018; 7(22): e009683. DOI: 10.1161/JAHA.118.009683

25. Babapoor-Farrokhran S., Gill D., Walker J., Rasekhi R.T., Bozorgnia B., Amanullah A. Myocardial injury and COVID-19: Possible mechanisms. Life Sci. 2020; 253: 117723. DOI: 10.1016/j.lfs.2020.117723

26. Florea V.G., Cohn J.N. The autonomic nervous system and heart failure. Circ. Res. 2014; 114(11): 18151826. DOI: 10.1161/CIRCRESAHA.114.302589

27. Xiong T.Y., Redwood S., Prendergast B., Chen M. Coronaviruses and the cardiovascular system: acute and long-term implications. Eur. Heart J. 2020; 41(19): 1798-1800. DOI: 10.1093/eurheartj/ehaa231

28. Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab. Syndr. 2020; 14(3): 247-250. DOI: 10.1016/j.dsx.2020.03.013

29. Thygesen K., Alpert J.S., Jaffe A.S., Chaitman B.R., Bax J.J., Morrow D.A., White H.D.; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J. Am. Coll. Cardiol. 2018; 72(18): 2231-2264. DOI: 10.1016/j.jacc.2018.08.1038

30. Chapman A.R., Shah A.S.V., Lee K.K., Anand A., Francis O., Adamson P., McAllister D.A., Strachan F.E., Newby D.E., Mills N.L. Long-Term Outcomes in Patients With Type 2 Myocardial Infarction and Myocardial Injury. Circulation. 2018; 137(12): 1236-1245. DOI: 10.1161/CIRCULATIONAHA.117.031806

31. Shi S., Qin M., Shen B., Cai Y., Liu T., Yang F., Gong W., Liu X., Liang J., Zhao Q., Huang H., Yang B., Huang C. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. J.A.M.A. Cardiol. 2020; 5(7): 802-810. DOI: 10.1001/jamacardio.2020.0950

32. Guo T., Fan Y., Chen M., Wu X., Zhang L., He T., Wang H., Wan J., Wang X., Lu Z. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). J.A.M.A. Cardiol. 2020; 5(7): 811-818. DOI: 10.1001/jamacardio.2020.1017

33. Lazzerini P.E., Capecchi P.L., Laghi-Pasini F. Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. Eur. Heart J. 2017; 38(22): 17171727. DOI: 10.1093/eurheartj/ehw208

34. Shao F., Xu S., Ma X., Xu Z., Lyu J., Ng M., Cui H., Yu C., Zhang Q., Sun P., Tang Z. Inhospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China. Resuscitation. 2020; 151: 18-23. DOI: 10.1016/j.resuscitation.2020.04.005

35. Turagam M.K., Musikantow D., Goldman M.E., Bassily-Marcus A., Chu E., Shivamurthy P., Lampert J., Kawamura I., Bokhari M., Whang W., Bier B.A., Malick W., Hashemi H., Miller M.A., Choudry S., Pumill C., Ruiz-Maya T., Hadley M., Giustino G., Koruth J.S., Langan N., Sofi A., Dukkipati S.R., Halperin J.L., Fuster V., Kohli-Seth R., Reddy V.Y. Malignant Arrhythmias in Patients With COVID-19: Incidence, Mechanisms, and Outcomes. Circ. Arrhythm. Electrophysiol. 2020; 13(11): e008920. DOI: 10.1161/CIR-CEP.120.008920

36. Mercuro N.J., Yen C.F., Shim D.J., Maher T.R., McCoy C.M., Zimetbaum P.J., Gold H.S. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). J.A.M.A. Cardiol. 2020; 5(9): 1036-1041. DOI: 10.1001/jamac-ardio.2020.1834. Erratum in: J.A.M.A. Cardiol. 2020; 5(9): 1071.

37. Ardashev A., Oseroff O., Sansalone R., Zhelyakov E.G., Cappato R., Snezhitskiy V., Kanorskii S., Abzalieva S., Belenkov Yu., Karpenko Yu., Puodziukynas A., Sayganov S.A., Santini L., Speranza R., Yakovleva M., Kolotsey L. Recommendations for the management of COVID 19 patients regarding proar-rhythmic effects of some current treatments, specifically if these patients suffer from arrhythmias, and for those receiving antiarrhythmic therapy. Kardiologiia. 2020; 60(10): 4-12 (In Russ., English abstract). DOI: 10.18087/cardio.2020.10.n1283

38. Bessiere F., Roccia H., Deliniere A., Chamere R., Chevalier P., Argaud L, Cour M. Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit. J.A.M.A. Cardiol. 2020; 5(9): 1067-1069. DOI: 10.1001/jamacar-dio.2020.1787

39. Lakkireddy D.R., Chung M.K., Gopinathannair R., Patton K.K., Gluckman T.J., Turagam M., Cheung J.W., Patel P., Sotomonte J., Lampert R., Han J.K., Rajago-palan B., Eckhardt L., Joglar J., Sandau K.E., Olshansky B., Wan E., Noseworthy P.A., Leal M., Kaufman E., Gutierrez A., Marine J.E., Wang P.J., Russo A.M. Guidance for cardiac electrophysiology during the COVID-19 pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American Heart Association. Heart Rhythm. 2020; 17(9): e233-e241. DOI: 10.1016/j.hrthm.2020.03.028

40. Chen D., Li X., Song Q., Hu C., Su F., Dai J., Ye Y., Huang J., Zhang X. Assessment of Hypokalemia and Clinical Characteristics in Patients With Coronavirus Disease 2019 in Wenzhou, China. J.A.M.A. Netw. Open. 2020; 3(6): e2011122. DOI: 10.1001/jamanet-workopen.2020.11122

41. Lippi G., Lavie C.J., Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog. Cardiovasc. Dis. 2020; 63(3): 390-391. DOI: 10.1016/j.pcad.2020.03.001

42. Bangalore S., Sharma A., Slotwiner A., Yatskar L., Harari R., Shah B., Ibrahim H., Friedman G.H., Thompson C., Alviar C.L., Chadow H.L., Fishman G.I., Reynolds H.R., Keller N., Hochman J.S. ST-Segment Elevation in Patients with Covid-19 — A Case Series. N. Engl. J. Med. 2020; 382(25): 2478-2480. DOI: 10.1056/NEJMc2009020

43. Levy B.I., Heusch G., Camici P.G. The many faces of myocardial ischaemia and angina. Cardiovasc. Res. 2019; 115(10): 1460-1470. DOI: 10.1093/cvr/cvz160

44. Welt F.G.P., Shah P.B., Aronow H.D., Bortnick A.E., Henry T.D., Sherwood M.W., Young M.N., Davidson L.J., Kadavath S., Mahmud E., Kirtane A.J.; American College of Cardiology’s Interventional Council and the Society for Cardiovascular Angiography and Interventions. Catheterization Laboratory Considerations During the Coronavirus (COVID-19) Pandemic: From the ACC’s Interventional Council and SCAI. J. Am. Coll. Cardiol. 2020; 75(18): 2372-2375. DOI: 10.1016/j.jacc.2020.03.021

45. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229): 1054-1062. DOI: 10.1016/S0140-6736(20)30566-3

46. Ruan Q., Yang K., Wang W., Jiang L., Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020; 46(5): 846-848. DOI: 10.1007/s00134-020-05991-x

47. Caro-Codon J., Rey J.R., Buno A., Iniesta A.M., Rosil-lo S.O., Castrejon-Castrejon S., Rodriguez-Sotelo L., Martinez L.A., Marco I., Merino C., Martin-Polo L., Garcia-Veas J.M., Martinez-Cossiani M., Gonzalez-Valle L., Herrero A., Lopez-de-Sa E., Merino J.L.; CARD-COVID Investigators. Characterization of NT-PROBNP in a large cohort of COVID-19 patients. Eur. J. Heart Fail. 2021. Online ahead of print. DOI: 10.1002/ejhf.2095

48. Shi S., Qin M., Cai Y., Liu T., Shen B., Yang F., Cao S., Liu X., Xiang Y., Zhao Q., Huang H., Yang B., Huang C. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur. Heart J. 2020; 41(22): 2070-2079. DOI: 10.1093/eurheartj/ehaa408

49. Golukhova E.Z., Slivneva I.V., Rybka M.M., Mama-lyga M.L., Marapov D.I., Klyuchnikov I.V., Antonova D.E., Dibin D.A. Right ventricular systolic dysfunction as a predictor of adverse outcome in patients with COVID-19. Kardiologiia. 2020; 60(11): 16-29 (In Russ., English abstract). DOI: 10.18087/car-dio.2020.11.n1303

50. Giustino G., Croft L.B., Stefanini G.G., Bragato R., Sil-biger J.J., Vicenzi M., Danilov T., Kukar N., Shaban N., Kini A., Camaj A., Bienstock S.W., Rashed E.R., Rahman K., Oates C.P., Buckley S., Elbaum L.S., Ar-konac D., Fiter R., Singh R., Li E., Razuk V., Robinson S.E., Miller M., Bier B., Donghi V., Pisaniello M., Mantovani R., Pinto G., Rota I., Baggio S., Chiarito M., Fazzari F., Cusmano I., Curzi M., Ro R., Malick W., Kamran M., Kohli-Seth R., Bassily-Marcus A.M., Neibart E., Serrao G., Perk G., Mancini D., Reddy V.Y, Pinney S.P., Dangas G., Blasi F., Sharma S.K., Mehran R., Condorelli G., Stone G.W., Fuster V., Lerakis S., Goldman M.E. Characterization of Myocardial Injury in Patients With COVID-19. J. Am. Coll. Cardiol. 2020; 76(18): 2043-2055. DOI: 10.1016/j.jacc.2020.08.069

51. Rey J.R., Caro-Codón J., Rosillo S.O., Iniesta Á.M., Castrejón-Castrejón S., Marco-Clement I., Martm-Polo L., Merino-Argos C., Rodnguez-Sotelo L., García-Veas J.M., Martmez-Mann L.A., Martmez-Cos-siani M., Buno A., Gonzalez-Valle L., Herrero A., Lopez-Sendon J.L., Merino J.L.; CARD-COVID Investigators. Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications. Eur. J. Heart Fail. 2020: 10.1002/ejhf.1990. Online ahead of print. DOI: 10.1002/ejhf.1990

52. Shlyakho E.V., Konradi A.O., Arutyunov G.P., Arutyunov A.G., Bautin A.E., Boytsov S.A., Villevalde S.V., Grigoryeva N.Yu., Duplyakov D.V., Zvartau N.E., Koziolova N.A., Lebedev D.S., Malchikova S.V., Medvedeva E.A., Mikhailov E.N., Moiseeva O.M., Orlova Y.A., Pavlova T.V., Pevsner D.V., Petrova M.M., Rebrov A.P., Sitnikova M.Yu., Solovyova A.E., Tarlovskaya E.I., Trukshina M.A., Fedotov P.A., Fomin I.V., Khripun A.V., Chesnikova A.I., Shaposhnik I.I., Yavelov I.S., Yakovlev A.N. Guidelines for the diagnosis and treatment of circulatory diseases in the context of the COVID-19 pandemic. Russian Journal of Cardiology. 2020; 25(3): 3801 (In Russ.). DOI: 10.15829/1560-4071-2020-3-3801

53. Shlyakhto Y.V., Arutyunov G.P., Belenkov Yu.N., Tarlovskaya E.I., Konradi A.O., Panchenko E.P., Yavelov I.S., Tereshchenko S.N., Ardashev A.V., Arutyunov A.G., Grigorieva N.Yu., Dzhunusbekova G.A., Drapkina O.M., Koziolova N.A., Komarov A.L., Kropacheva E.S., Malchikova S.V., Mitkovskaya N.P., Orlova Y.A., Petrova M.M., Rebrov A.P., Sisakian H., Skibitsky V.V., Sugraliyev A.B., Fomin I.V., Chesnikova A.I., Shaposhnik I.I., Zhelya-kov E.G., Kanorskii S.G., Kolotsey L.V., Snezhits-kiy V.A. Use of Statins, Anticoagulants, Antiaggregants and Antiarrhythmic Drugs in Patients With COVID-19. The Agreed Experts’ Position of Russian Society of Cardiology, Eurasian Association of Therapists, National Society on Atherothrombosis, Societies of Experts in Urgent Cardiology, Eurasian Ar-rhythmology Association. Kardiologiia. 2020; 60(6): 4-14 (In Russ., English abstract). DOI: 10.18087/cardio.2020.6.n1180

54. Lodigiani C., Iapichino G., Carenzo L., Cecconi M., Ferrazzi P., Sebastian T., Kucher N., Studt J.D., Sacco C., Bertuzzi A., Sandri M.T., Barco S.; Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb. Res. 2020; 191: 9-14. DOI: 10.1016/j.throm-res.2020.04.024

55. Klok F.A., Kruip M.J.H.A., van der Meer N.J.M., Arbous M.S., Gommers D.A.M.P.J., Kant K.M., Kaptein F.H.J., van Paassen J., Stals M.A.M., Huisman M.V., Endeman H. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020; 191: 145-147. DOI: 10.1016/j.thromres.2020.04.013

56. Oxley T.J., Mocco J., Majidi S., Kellner C.P., Shoirah H., Singh I.P., De Leacy R.A., Shigematsu T., Ladner T.R., Yaeger K.A., Skliut M., Weinberger J., Dangayach N.S., Bederson J.B., Tuhrim S., Fifi J.T. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N. Engl. J. Med. 2020; 382(20): e60. DOI: 10.1056/NEJMc2009787

57. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020; 18(4): 844-847. DOI: 10.1111/jth.14768

58. Wichmann D., Sperhake J.P., Lutgehetmann M., Steurer S., Edler C., Heinemann A., Heinrich F., Mushumba H., Kniep I., Schroder A.S., Burdelski C., de Heer G., Nierhaus A., Frings D., Pfefferle S., Becker H., Bredereke-Wiedling H., de Weerth A., Paschen H.R., Sheikhzadeh-Eggers S., Stang A., Schmiedel S., Bokemeyer C., Addo M.M., Aepfelbacher M., Puschel K., Kluge S. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann. Intern. Med. 2020; 173(4): 268-277. DOI: 10.7326/M20-2003

59. Vieillard-Baron A., Naeije R., Haddad F., Bogaard H.J., Bull T.M., Fletcher N., Lahm T., Magder S., Orde S., Schmidt G., Pinsky M.R. Diagnostic workup, etiologies and management of acute right ventricle failure: A state-of-the-art paper. Intensive Care Med. 2018; 44(6): 774-790. DOI: 10.1007/s00134-018-5172-2

60. Bikdeli B., Madhavan M.V., Jimenez D., Chuich T., Dreyfus I., Driggin E., Nigoghossian C., Ageno W., Madjid M., Guo Y., Tang L.V., Hu Y., Giri J., Cushman M., Quere I., Dimakakos E.P., Gibson C.M., Lippi G., Favaloro E.J., Fareed J., Caprini J.A., Tafur A.J., Burton J.R., Francese D.P., Wang E.Y., Falanga A., Mc-Lintock C., Hunt B.J., Spyropoulos A.C., Barnes G.D., Eikelboom J.W., Weinberg I., Schulman S., Carrier M., Piazza G., Beckman J.A., Steg P.G., Stone G.W., Rosenkranz S., Goldhaber S.Z., Parikh S.A., Monreal M., Krumholz H.M., Konstantinides S.V., Weitz J.I., Lip G.Y.H.; Global COVID-19 Thrombosis Collaborative Group, Endorsed by the ISTH, NATF, ESVM, and the IUA, Supported by the ESC Working Group on Pulmonary Circulation and Right Ventricular Function. 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(23): 2950-2973. DOI: 10.1016/j.jacc.2020.04.031

61. Wadhera R.K., Shen C., Gondi S., Chen S., Kazi D.S., Yeh R.W. Cardiovascular Deaths During the COVID-19 Pandemic in the United States. J. Am. Coll. Cardiol. 2021; 77(2): 159-169. DOI: 10.1016/j.jacc.2020.10.055

62. Bhatt A.S., Moscone A., McElrath E.E., Varshney A.S., Claggett B.L., Bhatt D.L., Januzzi J.L., Butler J., Adler D.S., Solomon S.D., Vaduganathan M. Fewer Hospitalizations for Acute Cardiovascular Conditions During the COVID-19 Pandemic. J. Am. Coll. Cardiol. 2020; 76(3): 280-288. DOI: 10.1016/j.jacc.2020.05.038

63. Lai P.H., Lancet E.A., Weiden M.D., Webber M.P., Zeig-Owens R., Hall C.B., Prezant D.J. Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City. J.A.M.A. Cardiol. 2020; 5(10): 1154-1163. DOI: 10.1001/jamacardio.2020.2488

64. Einstein A.J., Shaw L.J., Hirschfeld C., Williams M.C., Villines T.C., Better N., Vitola J.V., Cerci R., Dorbala S., Raggi P., Choi A.D., Lu B., Sinitsyn V., Sergienko V., Kudo T., N0rgaard B.L., Maurovich-Horvat P., Campisi R., Milan E., Louw L., Allam A.H., Bhatia M., Malkovskiy E., Goebel B., Cohen Y., Randazzo M., Narula J., Pascual T.N.B., Pynda Y., Don-di M., Paez D.; INCAPS COVID Investigators Group. International Impact of COVID-19 on the Diagnosis of Heart Disease. J. Am. Coll. Cardiol. 2021; 77(2): 173185. DOI: 10.1016/j.jacc.2020.10.054

65. Puntmann V.O., Carerj M.L., Wieters I., Fahim M., Arendt C., Hoffmann J., Shchendrygina A., Escher F., Vasa-Nicotera M., Zeiher A.M., Vehreschild M., Nagel E. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). J.A.M.A. Cardiol. 2020; 5(11): 1265-1273. DOI: 10.1001/jamacar-dio.2020.3557