Does SARS-CoV-2 infect cardiomyocytes directly? Yes, it does
, 1
Abstract
Introduction: COVID-19 (Coronavirus disease 2019) appeared in Wuhan, China, at the ending of 2019. The SARS-CoV-2 virus which causes the illness has spread all over the world and caused a pandemic. The first target of the virus is the respiratory tract; however, the COVID-19 may present different types of course. It is known that the SARS-CoV-2 affects multiple organs, including the heart. Cardiac manifestations of COVID-19 include myocarditis, myocardial infarction, heart failure, acute coronary syndrome, arrhythmia. The authors know about the patients who had only cardiovascular complications due to the COVID-19. Several mechanisms of heart injury are considered and so is the direct infection.
Aim of the study: The present review aimed to find out if the SARS-CoV-2 may infect the heart directly and in which mechanism. The review is an information collection considering the SARS-CoV-2 impact on the heart.
Material and methods: The authors have made research using the PubMed search engine to find studies and case reports considering the cardiovascular implications of COVID-19. The signs and symptoms in patients with cardiac implications were studied. The authors have also checked if studies explaining does the SARS-CoV-2 affects the heart directly were conducted.
Results: SARS-CoV-2 brings several cardiovascular signs such as changes in imaging tests and elevation of several laboratory markers. The changes may suggest myocarditis or mimic cardiac infarction. The SARS-CoV-2 may affect cardiomyocytes indirectly by causing hypoxia and cytokine storm. As the heart tissue presents a high level of ACE2 which is the target of the virus, the SARS-CoV may infect cardiomyocytes directly. The hypothesis was confirmed in endomyocardial biopsies, autopsy, and in vitro studies.
Conclusions: The SARS-CoV-2 impacts several organs. The heart may be injured indirectly (hypoxia and cytokine storm) and directly (ACE2 present in the heart), which gives consequences in a clinical course. The direct injury was confirmed in a variety of ways.
Keywords: SARS-CoV-2COVID-19cardiomyocyte
References
- Bogoch II, Watts A, Thomas-Bachli A, et al. Pneumonia of unknown aetiology in Wuhan, China: potential for international spread via commercial air travel. J Travel Med. 2020; 27(2).
- Zheng J. SARS-CoV-2: an emerging coronavirus that causes a global threat. Int J Biol Sci. 2020; 16(10): 1678–1685.
- WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 (10.04.2021).
- WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int/ (27.05.2021).
- García LF. Immune response, inflammation, and the clinical spectrum of COVID-19. Front Immunol. 2020; 11: 1441.
- Goha A, Mezue K, Edwards P, et al. COVID-19 and the heart: An update for clinicians. Clin Cardiol. 2020; 43(11): 1216–1222.
- Behzad S, Aghaghazvini L, Radmard AR, et al. Extrapulmonary manifestations of COVID-19: Radiologic and clinical overview. Clin Imaging. 2020; 66: 35–41.
- Zeng JH, Liu YX, Yuan J, et al. First case of COVID-19 complicated with fulminant myocarditis: a case report and insights. Infection. 2020; 48(5): 773–777.
- Fried J, Ramasubbu K, Bhatt R, et al. The Variety of cardiovascular presentations of COVID-19. Circulation. 2020; 141(23): 1930–1936.
- Inciardi R, Lupi L, Zaccone G, et al. Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19). JAMA Cardiology. 2020; 5(7): 819–824.
- Kazi DS, Martin LM, Litmanovich D, et al. Case 18-2020: A 73-year-old man with hypoxemic respiratory failure and cardiac dysfunction. N Engl J Med. 2020; 382(24): 2354–2364.
- Newton-Cheh C, Zlotoff DA, Hung J, et al. Case 24-2020: A 44-year-old woman with chest pain, dyspnea, and shock. N Engl J Med. 2020; 383(5): 475–484.
- Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiology. 2020; 5(7): 811–818.
- Stone JR, Tran KM, Conklin J, et al. Case 23-2020: A 76-year-old woman who died from Covid-19. N Engl J Med. 2020; 383(4): 380–387.
- Ho JSy, Tambyah PA, Ho AFw, et al. Effect of coronavirus infection on the human heart: A scoping review. Eur J Prev Cardiol. 2020; 27(11): 1136–1148.
- Leone O, Pieroni M, Rapezzi C, et al. The spectrum of myocarditis: from pathology to the clinics. Virchows Arch. 2019; 475(3): 279–301.
- Ho JSy, Sia CH, Chan MYy, et al. Coronavirus-induced myocarditis: A meta-summary of cases. Heart Lung. 2020; 49(6): 681–685.
- Coronavirus-induced myocarditis: A meta-summary of cases. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440036/ (Mar. 14, 2021).
- Shi S, Qin Mu, Shen Bo, et al. Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020; 5(7): 802–810.
- 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. The Lancet. 2020; 395(10229): 1054–1062.
- Zou X, Chen Ke, Zou J, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020; 14(2): 185–192.
- Hikmet F, Méar L, Edvinsson Å, et al. The protein expression profile of ACE2 in human tissues. Mol Syst Biol. 2020; 16(7): e9610.
- Rahman N, Basharat Z, Yousuf M, et al. Virtual screening of natural products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2) . Molecules. 2020; 25(10).
- Topol EJ. COVID-19 can affect the heart. Science. 2020; 370(6515): 408–409.
- Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020; 14(3): 247–250.
- Akhmerov A, Marbán E. COVID-19 and the heart. Circ Res. 2020; 126(10): 1443–1455.
- Bailey AL, Dmytrenko O, Greenberg L, et al. SARS-CoV-2 infects human engineered heart tissues and models COVID-19 myocarditis. JACC Basic Transl Sci. 2021; 6(4): 331–345.
- Bojkova D, Wagner JUG, Shumliakivska M, et al. SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes. Cardiovasc Res. 2020; 116(14): 2207–2215.
- Sharma A, Garcia G, Arumugaswami V, et al. Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 infection. Cell Rep Med. 2020; 1(4).
- Wenzel P, Kopp S, Göbel S, et al. Evidence of SARS-CoV-2 mRNA in endomyocardial biopsies of patients with clinically suspected myocarditis tested negative for COVID-19 in nasopharyngeal swab. Cardiovasc Res. 2020; 116(10): 1661–1663.
- 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(5): 2440–2447.
- Tavazzi G, Pellegrini C, Maurelli M, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020; 22(5): 911–915.
- Varga Z, Flammer A, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020; 395(10234): 1417–1418.
- 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(11): 1281–1285.
- Pesaresi M, Pirani F, Tagliabracci A, et al. SARS-CoV-2 identification in lungs, heart and kidney specimens by transmission and scanning electron microscopy. Eur Rev Med Pharmacol Sci. 2020; 24(9): 5186–5188.
- Bradley B, Maioli H, Johnston R, et al. Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. The Lancet. 2020; 396(10247): 320–332.
- Bulfamante GP, Perrucci GL, Falleni M, et al. Evidence of SARS-CoV-2 transcriptional activity in cardiomyocytes of COVID-19 patients with outclinical signs of cardiac involvement. Biomedicines. 2020; 8(12).