Iberoamerican Journal of Medicine
Iberoamerican Journal of Medicine

Demystifying the conundrum of COVID-19 and cardiovascular system

Debabrata Dash

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The outbreak of novel Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic and a public health crisis. COVID-19 is the clinical manifestation of infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Although it is predominantly a respiratory illness, there is growing awareness of the cardiovascular manifestations of COVID-19 disease. Patients with pre-existing cardiovascular co-morbidities appear to be at highest risk for mortality from this disease along with the elderly. COVID-19 also contributes to cardiovascular complications, including myocardtits, acute coronary syndromes, arrhythmias, acute heart failure, and, in the most severe cases, cardiogenic shock and death. Several medications proposed in the treatment of this infection have cardiac-specific adverse effects that warrant cardiac monitoring. This review summarizes the rapidly emerging data on the cardiovascular implications of COVID-19.


COVID-19; SARS-CoV-2; Myocarditis; Heart failure; Arrhythmia


1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. 2020. doi: 10.1001/jama.2020.2648.
2. World Health Organization (WHO). The World Health Organization Coronavirus disease 2019 (COVID-19) situation report e61. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200321-sitrep-61-covid-19.pdf? sfvrsn¼f201f85c_2. (accessed April 2020).
3. Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020. doi: 10.1111/all.14238.
4. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020; 323(11):1061-9. doi: 10.1001/jama.2020.1585.
5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5.
6. Turner AJ, Hiscox JA, Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. Trends Pharmacol Sci. 2004;25(6):291-4. doi: 10.1016/j.tips.2004.04.001.
7. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3. doi: 10.1038/s41586-020-2012-7.
8. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS.. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46(4):586-90. doi: 10.1007/s00134-020-05985-9.
9. Zhang S, Diao M, Yu W, Peil L, Lin Z, Chen D. Estimation of the reproductive number of novel coronavirus (COVID-19) and the probable outbreak size on the Diamond Princess cruise ship: A data-driven analysis. Int J Infect Dis. 2020;93:201-4. doi: 10.1016/j.ijid.2020.02.033.
10. World Health Organization. Coronavirus Disease 2019 (COVID-19) Situation report - 46.Available from: https://www.who.int/docs/default-source/coronaviruse/situationreports/ 20200306-sitrep-46-covid- 19.pdf?sfvrsn=96b04adf_2 (accessed on March 2020).
11. Mizumoto K, Kagaya, K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the diamond princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 2020; 25(10):2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180.
12. Murthy S, Gomersall CD, Fowler RA. Care for critically ill patients with COVID-19. JAMA. 2020. doi: 10.1001/jama.2020.3633.
13. 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):846-8. doi: 10.1007/s00134-020-05991-x.
14. Chen W-H, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 vaccine pipeline: an overview. Curr Trop Med Rep. 2020;1-4. doi: 10.1007/s40475-020-00201-6.
15. Zidar DA, Al-Kindi SG, Liu Y, Krieger NI, Perzynski AT, Osnard M, et al. Association of lymphopenia with risk of mortality among adults in the US general population. JAMA Netw Open. 2019;2(12):e1916526. doi: 10.1001/jamanetworkopen.2019.16526.
16. Libby P, Ridker PM, Hansson GK, Leducq Transatlantic Network on Atherothrombosis. Inflammation in Atherosclerosis: From Pathophysiology to Practice. J Am Coll Cardiol. 2009;54(23):2129-38. doi: 10.1016/j.jacc.2009.09.009.
17. Tall AR, Yvan-Charvet L. Cholesterol, inflammation and innate immunity. Nat Rev Immunol. 2015;15(2):104-16. doi: 10.1038/nri3793.
18. Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017;127(1):1-4. doi: 10.1172/JCI92035.
19. Zheng YY, Ma YT, Zhang JY, et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17(5):259-60. doi: 10.1038/s41569-020-0360-5.
20. Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;09(5):531-8. doi: 10.1007/s00392-020-01626-9.
21. Sarkisian L, Saaby L, Poulsen TS, Gerke O, Jangaard N, Hosbond S, et al. Clinical characteristics and outcomes of patients with myocardial Infarction, myocardial Injury, and nonelevated troponins. Am J Med. 2016;129(4):446 e5-446 e21. doi: 10.1016/j.amjmed.2015.11.006.
22. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;72(18):2231-64. doi: 10.1016/j.jacc.2018.08.1038.
23. Zhou F, Yu T, Du R, Fan G, Liu L, Liu Z, et al. Clinical course and risk factors for mortality of adult in patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. doi: 10.1016/S0140-6736(20)30566-3.
24. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-81. doi: 10.1016/S2213-2600(20)30079-5.
25. 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. doi: 10.1016/j.pcad.2020.03.001.
26. Alhogbani T. Acute myocarditis associated with novel middle east respiratory syndrome coronavirus. Ann Saudi Med 2016;36(1):78-80. doi: 10.5144/0256-4947.2016.78.
27. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420-2. doi: 10.1016/S2213-2600(20)30076-X.
28. Liu Y, Yang Y, Zhang C, Wang F, Yuan G, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-74. doi: 10.1007/s11427-020-1643-8.
29. Liu K, Fang YY, Deng Y, Liu W, Wang MF, Ma JP, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;5;133(9):1025-31. doi: 10.1097/CM9.0000000000000744.
30. Hua A, O’Gallagher K, Sado D, Byrne J. Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19. Eur Heart J. 2020;ehaa253. doi: 10.1093/eurheartj/ehaa253.
31. Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med. 2018;378(4):345-53. doi: 10.1056/NEJMoa1702090.
32. Wood S. TCT the Heat Beat: COVID-19 and the Heart: Insights from the Front Lines. Available from: https://www.tctmd.com/news/covid-19-and-heart-insights-front-lines. (accessed March 2020).
33. Hui H, Zhang Y, Yang X, Wang X, He B, Li L, et al. Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia. MedRxiv. 2020. doi: https://doi.org/10.1101/2020.02.24.20027052.
34. Rali AS, Sauer AJ. COVID-19 pandemic and cardiovascular disease. US Cardiology Review. 2020;14:e01. doi: https://doi.org/10.15420/usc.2020.14.
35. Chen C, Zhou Y, Wang DW. SARS-CoV-2: a potential novel etiology of fulminant myocarditis. Herz. 2020;45(3):230-2. doi: 10.1007/s00059-020-04909-z.
36. Buzon J, Roignot O, Lemoine S, Perez P, Kimmoun A, Levy B, et al. Takotsubo cardiomyopathy triggered by influenza A virus. Intern Med 2015;54(16):2017-9. doi: 10.2169/internalmedicine.54.3606.
37. Driggin E, Madhavan MV, Bikdeli B, Chuich T, Laracy J, Biondi-Zoccai G, et al. Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) Pandemic. J Am Coll Cardiol. 2020;75(18):2352-71. doi: 10.1016/j.jacc.2020.03.031.
38. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and Cardiovascular Disease. Circulation. 2020;141(20):1648-55. doi: 10.1161/CIRCULATIONAHA.120.046941.
39. Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38(10):1573-82. doi: 10.1007/s00134-012-2682-1.
40. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-33. doi: 10.1001/jama.2012.5669.
41. Karmpaliotis D, Kirtane AJ, Ruisi CP, Polonsky T, Malhotra A, Talmor D, et al. Diagnostic and prognostic utility of brain natriuretic peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema. Chest. 2007;131(4):964-71. doi: 10.1378/chest.06-1247.
42. MacLaren G, Fisher D, Brodie D. Preparing for the most critically ill patients with COVID-19: The potential role of extracorporeal membrane oxygenation. JAMA. 2020. doi: 10.1001/jama.2020.2342.
43. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. doi: 10.1016/S0140-6736(20)30211-7.
44. 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):844-7. doi: 10.1111/jth.14768.
45. Fan BE, Chong VCL, Chan SSW, Lim GH, Lim KGE, Tan GB, et al. Hematologic parameters in patients with COVID-19 infection. Am J Hematol. 2020;95(6):E131-E134. doi: 10.1002/ajh.25774.
46. Wang T, Chen R, Liu C, Liang W, Guan W, Tang R, et al. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol. 2020;7(5):e362-e363. doi: 10.1016/S2352-3026(20)30109-5.
47. Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018;2(22):3257-91. doi: 10.1182/bloodadvances.2018024893.
48. Li F, Cai J, Dong N. First cases of COVID-19 in heart transplantation from China. J Heart Lung Transplant. 2020;39(5):496-7. doi: 10.1016/j.healun.2020.03.006.
49. Aslam S, Mehra MR. COVID-19: Yet another coronavirus challenge in transplantation. J Heart Lung Transplant. 2020;39(5):408-9. doi: 10.1016/j.healun.2020.03.007.
50. Ren ZL, Hu R, Wang ZW, Zhang M, Ruan YL, Wu ZY, et al. Epidemiologic and clinical characteristics of heart transplant recipients during the 2019 coronavirus outbreak in Wuhan, China: a descriptive survey report. J Heart Lung Transplant. 2020.39(5):412-7. doi: 10.1016/j.healun.2020.03.008.
51. Guidance for Cardiothoracic Transplant and Mechanical Circulatory Support Centers regarding SARS CoV-2 infection and COVID-19. Available from: https://community.ishlt.org/HigherLogic/System/DownloadDocumentFile.ashx?DocumentFileK ey=afb06f06-5d63-13d4-c107-d152a9f6cd46. (accessed March 2020)
52. American Society of Transplantation. 2019-nCoV (Coronavirus): FAQs for Organ Transplantation. Updated Feb 29, 2020. Available from: https://www.myast.org/sites/default/files/COVID19%20FAQ%20Tx%20Centers%20030220-1.pdf. (accessed March 2020)
53. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q, Meredith HR, et al. The Incubation period of Coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: estimation and application. Ann Intern Med. 2020;172(9):577-82. doi: 10.7326/M20-0504.
54. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus infected pneumonia. New Eng J Med. 2020;382(13):1199-207. doi: 10.1056/NEJMoa2001316.
55. Khalili JS, Zhu H, Mak NSA, Yan Y, Zhu Y. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID-19. J Med Virol. 2020. doi: 10.1002/jmv.25798.
56. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787‐99. doi: 10.1056/NEJMoa2001282.
57. DeCarolis DD, Westanmo AD, Chen YC, Boese AL, Walquist MA, Rector TS. Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin. Ann Pharmacother. 2016;50(11):909-17. doi: 10.1177/1060028016660325.
58. Frost CE, Byon W, Song Y, Wang J, Schuster AE, Boyd RA, et al. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. Br J Clin Pharmacol. 2015;79(5):838-46. doi: 10.1111/bcp.12541.
59. Mueck W, Kubitza D, Becka M. Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol. 2013;76(3):455-66. doi: 10.1111/bcp.12075.
60. Máchal J, Hlinomaz O. Efficacy of P2Y12 Receptor Blockers After Myocardial Infarction and Genetic Variability of their Metabolic Pathways. Curr Vasc Pharmacol. 2019;17(1):35‐40. doi: 10.2174/1570161116666180206110657.
61. Azran M, Tanaka KA. Interaction Between Ticagrelor and CYP3A4 Inhibitor: Importance of P2Y12 Function Testing to Assess Platelet Recovery Before Surgery. J Cardiothorac Vasc Anesth. 2019;33(11):3221‐2. doi: 10.1053/j.jvca.2019.05.004.
62. Itkonen MK, Tornio A, Lapatto-Reiniluoto O, Neuvonen M, Neuvonen PJ, Niemi M, et al. Clopidogrel increases dasabuvir exposure with or without ritonavir, and ritonavir Inhibits the bioactivation of clopidogrel. Clin Pharmacol Ther. 2019;105(1):219-28. doi: 10.1002/cpt.1099.
63. Marsousi N, Daali Y, Fontana P, Reny JL, Ancrenaz-Sirot V, Calmy A, et al. Impact of boosted antiretroviral therapy on the pharmacokinetics and efficacy of clopidogrel and prasugrel active metabolites. Clin Pharmacokinet 2018;57(10):1347-54. doi: 10.1007/s40262-018-0637-6.
64. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69. doi: 10.1186/1743-422X-2-69.
65. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30:269-71. doi: 10.1038/s41422-020-0282-0.
66. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-3. doi: 10.5582/bst.2020.
67. Page RL 2nd, O'Bryant CL, Cheng D, Dow TJ, Ky B, Stein CM, et al. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016;134(6):e32-69. doi: 10.1161/CIR.0000000000000426.
68. Tonnesmann E, Kandolf R, Lewalter T. Chloroquine cardiomyopathy - a review of the literature. Immunopharmacol Immunotoxicol. 2013;35(3):434-42. doi: 10.3109/08923973.2013.780078.
69. Arai T, Yasuda Y, Takaya T, Toshima S, Kashiki Y, Yoshimi N, et al. ACE inhibitors and reduction of the risk of pneumonia in elderly people. Am J Hypertens. 2000;13(9):1050-1. doi: 10.1016/s0895-7061(00)00301-0.
70. Shinohara Y, Origasa H. Post-stroke pneumonia prevention by angiotensin-converting enzyme inhibitors: results of a meta-analysis of five studies in Asians. Adv Ther. 2012;29(10):900-12. doi: 10.1007/s12325-012-0049-1.
71. Caldeira D, Alarcão J, Vaz-Carneiro A, Costa J. Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis. BMJ. 2012;345:e4260. doi: 10.1136/bmj.e4260.
72. de Simone G. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. March 13, 2020. Available
from: https://www.escardio.org/Councils/ Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang (accessed March 2020).
73. The World Health Organization. WHO Infection Prevention and Control Guidance for COVID-19. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/infection-prevention-and- control. (accessed April 2020)
74. Welt FGP, Shah PB, Aronow HD, Bornick AE, Henry TD, Sherwood MW, et al. Catheterizatiion laboratory considerations during the coronavirus (COVID-19) pandemic. From ACC’s Interventional Council and SCAI. J Am Coll Cardiol. 2020;75(18):2372-5. doi: 10.1016/j.jacc.2020.03.021.
75. Chow TT, Kwan A, Lin Z, Bai W. Conversion of operating theatre from positive to negative pressure environment. J Hosp Infect. 2006;64(4):371-8. doi: 10.1016/j.jhin.2006.07.020.
76. Hollander JE, Carr BG. Virtually perfect? Telemedicine for Covid-19. N Engl J Med. 2020;382(18):1679-81. doi: 10.1056/NEJMp2003539.
77. American College of Cardiology. COVID-19 Clinical Guidance For the Cardiovascular Care Team. Available online: https://www.acc.org//~/media/Non-Clinical/Files-PDFs-Excel-MSWord-etc/2020/02/S20028-ACC-Clinical-Bulletin-Coronavirus.pdf (accessed March 2020).
78. European Society of Cardiology. Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers. Available from: https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang. (accessed May 2020)
79. Hypertension Canada. Hypertension Canada’s Statement on: Hypertension, ACE-Inhibitors and Angiotensin Receptor Blockers and COVID-19. Availñable from: https://hypertension.ca/wp-content/uploads/2020/03/2020-30-15-Hypertension-Canada-Statement-on-COVID-19-ACEi-ARB.pdf. (accessed May 2020)
80. Canadian Cardiovascular Society. COVID-19 and concerns regarding use of ACEi/ARB/ARNi medications for heart failure or hypertension. Available from: https://www.ccs.ca/images/Images_2020/CCS_CHFS_statement_regarding_COVID_EN.pdf. (accessed May 2020)
81. International Society of Hypertension. A statement from the International Society of Hypertension on COVID-19. Available from: https://ish-world.com/news/a/A-statement-from-the-International-Society-of-Hypertension-on-COVID-19/. (accessed May 2020)
82. Mahmud E, Dauerman HL, Welt FG, Messenger JC, Rao SV, Grines C, et al. Management of acute myocardial infarction during the COVID-19 Pandemic. J Am Coll Cardiol. 2020;S0735-1097(20)35026-9. doi: 10.1016/j.jacc.2020.04.039.
83. Zeng J, Huang J, Pan L. How to balance acute myocardial infarction and COVID-19: the protocols from Sichuan Provincial People’s Hospital. Intensive Care Med. 2020;1-3. doi: 10.1007/s00134-020-05993-9.

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