The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.

Laboratory of Neurobiology and Molecular Psychiatry Department of Biochemistry Faculty of Science Masaryk University Brno Czech Republic

See more in PubMed

Dziedzinska R, Kralik P, Šerý O. Occurrence of SARS-CoV-2 in indoor environments with increased circulation and gathering of people. Front Public Health. 2021;9:787841. doi: 10.3389/fpubh.2021.787841. PubMed DOI PMC

Kessler M, Vojtíšek T, Zeman T, Krajsa J, Srník M, Kralik P, Dziedzinska R, Šerý O. The protective effect of serum antibodies in preventing of SARS-CoV-2 virus entry into cardiac muscle. Physiol Res. 2024;73(Suppl 3):S715–S725. PubMed PMC

Wang YX, Wang YY, Chen Y, Qin QS. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020;92:568–576. doi: 10.1002/jmv.25748. PubMed DOI PMC

Kounis NG, Gogos C, de Gregorio C, Hung MY, Kounis SN, Tsounis EP, Assimakopoulos SF, et al. “When,” “where,” and “how” of SARS-CoV-2 infection affects the human cardiovascular system: A narrative review. Balkan Med J. 2024;41:7–22. doi: 10.4274/balkanmedj.galenos.2023.2023-10-25. PubMed DOI PMC

Salon A, Neshev R, Teraz K, Simunic B, Peskar M, Marusic U, Pisot S, et al. A pilot study: Exploring the influence of COVID-19 on cardiovascular physiology and retinal microcirculation. Microvasc Res. 2023;150:104588. doi: 10.1016/j.mvr.2023.104588. PubMed DOI

Ciabatti M, Zocchi C, Olivotto I, Bolognese L, Pieroni M. Myocarditis and COVID-19 related issues. Glob Cardiol Sci Pract. 2023;2023:e202328. doi: 10.21542/gcsp.2023.28. PubMed DOI PMC

V’Kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. Coronavirus biology and replication: Implications for SARS-CoV-2. Nat Rev Microbiol. 2021;19:155–170. doi: 10.1038/s41579-020-00468-6. PubMed DOI PMC

Gorbalenya AE, Enjuanes L, Ziebuhr J, Snijder EJ. Nidovirales: evolving the largest RNA virus genome. Virus Res. 2006;117:17–37. doi: 10.1016/j.virusres.2006.01.017. PubMed DOI PMC

Zheng G, Qiu G, Qian H, Shu Q, Xu J. Multifaceted role of SARS-CoV-2 structural proteins in lung injury. Front Immunol. 2024;15:1332440. doi: 10.3389/fimmu.2024.1332440. PubMed DOI PMC

Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41:1141–1149. doi: 10.1038/s41401-020-0485-4. PubMed DOI PMC

Belouzard S, Millet JK, Licitra BN, Whittaker GR. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. 2012;4:1011–1033. doi: 10.3390/v4061011. PubMed DOI PMC

Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci U S A. 2009;106:5871–5876. doi: 10.1073/pnas.0809524106. PubMed DOI PMC

Navaratnarajah CK, Pease DR, Halfmann PJ, Taye B, Barkhymer A, Howell KG, Charlesworth JE, et al. Highly efficient SARS-CoV-2 infection of human cardiomyocytes: Spike protein-mediated cell fusion and its inhibition. J Virol. 2021;95:e0136821. doi: 10.1128/JVI.01368-21. PubMed DOI PMC

Cai Y, Zhang J, Xiao T, Peng H, Sterling SM, Walsh RM, Jr, Rawson S, Rits-Volloch S, Chen B. Distinct conformational states of SARS-CoV-2 spike protein. Science. 2020;369:1586–1592. doi: 10.1126/science.abd4251. PubMed DOI PMC

Hoffmann M, Kleine-Weber H, Pöhlmann S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell. 2020;78:779–784.e775. doi: 10.1016/j.molcel.2020.04.022. PubMed DOI PMC

Bai Z, Cao Y, Liu W, Li J. The SARS-CoV-2 nucleocapsid protein and its role in viral structure, biological functions, and a potential target for drug or vaccine mitigation. Viruses. 2021;13:1115. doi: 10.3390/v13061115. PubMed DOI PMC

Lu X, Pan J, Tao J, Guo D. SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism. Virus Genes. 2011;42:37–45. doi: 10.1007/s11262-010-0544-x. PubMed DOI PMC

Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge. Virol J. 2019;16:69. doi: 10.1186/s12985-019-1182-0. PubMed DOI PMC

Nieto-Torres JL, Dediego ML, Alvarez E, Jiménez-Guardeño JM, Regla-Nava JA, Llorente M, Kremer L, et al. Subcellular location and topology of severe acute respiratory syndrome coronavirus envelope protein. Virology. 2011;415:69–82. doi: 10.1016/j.virol.2011.03.029. PubMed DOI PMC

Verdiá-Báguena C, Nieto-Torres JL, Alcaraz A, DeDiego ML, Torres J, Aguilella VM, Enjuanes L. Coronavirus E protein forms ion channels with functionally and structurally-involved membrane lipids. Virology. 2012;432:485–494. doi: 10.1016/j.virol.2012.07.005. PubMed DOI PMC

Zhang Z, Nomura N, Muramoto Y, Ekimoto T, Uemura T, Liu K, Yui M, et al. Structure of SARS-CoV-2 membrane protein essential for virus assembly. Nat Commun. 2022;13:4399. doi: 10.1038/s41467-022-32019-3. PubMed DOI PMC

He RT, Leeson A, Ballantine M, Andonov A, Baker L, Dobie F, Li Y, et al. Characterization of protein-protein interactions between the nucleocapsid protein and membrane protein of the SARS coronavirus. Virus Res. 2004;105:121–125. doi: 10.1016/j.virusres.2004.05.002. PubMed DOI PMC

Kumar P, Kumar A, Garg N, Giri R. An insight into SARS-CoV-2 membrane protein interaction with spike, envelope, and nucleocapsid proteins. J Biomol Struct Dyn. 2023;41:1062–1071. doi: 10.1080/07391102.2021.2016490. PubMed DOI

Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab. 2004;15:166–169. doi: 10.1016/j.tem.2004.03.001. PubMed DOI PMC

Zhou L, Niu Z, Jiang X, Zhang Z, Zheng Y, Wang Z, Zhu Y, et al. SARS-CoV-2 targets by the pscRNA profiling of ACE2, TMPRSS2 and furin proteases. iScience. 2020;23:101744. doi: 10.1016/j.isci.2020.101744. PubMed DOI PMC

Padmanabhan P, Desikan R, Dixit NM. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection. PLoS Comput Biol. 2020;16:e1008461. doi: 10.1371/journal.pcbi.1008461. PubMed DOI PMC

Koch J, Uckeley ZM, Doldan P, Stanifer M, Boulant S, Lozach PY. TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells. EMBO J. 2021;40:e107821. doi: 10.15252/embj.2021107821. PubMed DOI PMC

Moscucci F, Gallina S, Bucciarelli V, Aimo A, Pelà G, Cadeddu-Dessalvi C, Nodari S, et al. Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on ‘gender cardiovascular diseases’. J Cardiovasc Med (Hagerstown) 2023;24(Suppl 1):E15–E23. doi: 10.2459/JCM.0000000000001398. PubMed DOI PMC

Penna C, Mercurio V, Tocchetti CG, Pagliaro P. Sex-related differences in COVID-19 lethality. Br J Pharmacol. 2020;177:4375–4385. doi: 10.1111/bph.15207. PubMed DOI PMC

Sharma A, Garcia G, Wang YZ, Plummer JT, Morizono K, Arumugaswami V, Svendsen CN. Human iPSC-derived cardiomyocytes are susceptible to SARS-CoV-2 infection. Cell Rep Med. 2020;1:100052. doi: 10.1101/2020.04.21.051912. PubMed DOI PMC

Bojkova D, Wagner JUG, Shumliakivska M, Aslan GS, Saleem U, Hansen A, Luxán G, et al. SARS-CoV-2 infects and induces cytotoxic effacts in human cardiomyocytes. Cardiovasc Res. 2020;116:2207–2215. doi: 10.1093/cvr/cvaa267. PubMed DOI PMC

Lee CY, Huang CH, Rastegari E, Rengganaten V, Liu PC, Tsai PH, Chin YF, et al. Tumor necrosis factor-alpha exacerbates viral entry in SARS-CoV2-infected iPSC-derived cardiomyocytes. Int J Mol Sci. 2021;22:9869. doi: 10.3390/ijms22189869. PubMed DOI PMC

Gauchotte G, Venard V, Segondy M, Cadoz C, Esposito-Fava A, Barraud D, Louis G. SARS-Cov-2 fulminant myocarditis: An autopsy and histopathological case study. Int J Legal Med. 2021;135:577–581. doi: 10.1007/s00414-020-02500-z. PubMed DOI PMC

Chen L, Li XJ, Chen MQ, Feng Y, Xiong CL. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116:1097–1100. doi: 10.1093/cvr/cvaa078. PubMed DOI PMC

Qi J, Zhou Y, Hua J, Zhang LY, Bian JL, Liu BB, Zhao ZC, Jin SL. The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to SARS-CoV-2 infection. Int J Environ Res Public Health. 2021;18:284. doi: 10.3390/ijerph18010284. PubMed DOI PMC

Huang JY, Guo ZB, Duan JK, Zou Y, Chen K, Huang H, Zhang S, Zhou YG. Tissue expression of the SARS-CoV-2 cell receptor gene ACE2 in children. J Trop Pediatr. 2023;69:fmad027. doi: 10.1093/tropej/fmad027. PubMed DOI

Schurink B, Roos E, Radonic T, Barbe E, Bouman CSC, de Boer HH, de Bree GJ, et al. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe. 2020;1:E290–E299. doi: 10.1016/S2666-5247(20)30144-0. PubMed DOI PMC

Ren J, Zhang YZ, Liu SS, Li XJ, Sun XG. Detailed analyses of the expression patterns of potential severe acute respiratory syndrome Coronavirus 2 receptors in the human heart using single-nucleus RNA sequencing. Front Cardiovasc Med. 2021;8:757362. doi: 10.3389/fcvm.2021.757362. PubMed DOI PMC

Hanson PJ, Liu-Fei F, Ng C, Minato TA, Lai C, Hossain AR, Chan R, et al. Characterization of COVID-19-associated cardiac injury: evidence for a multifactorial disease in an autopsy cohort. Lab Invest. 2022;102:814–825. doi: 10.1038/s41374-022-00783-x. PubMed DOI PMC

Bristow MR, Zisman LS, Altman NL, Gilbert EM, Lowes BD, Minobe WA, Slavov D, et al. Dynamic regulation of SARS-CoV-2 binding and cell entry mechanisms in remodeled human ventricular myocardium. JACC Basic Transl Sci. 2020;5:871–883. doi: 10.1016/j.jacbts.2020.06.007. PubMed DOI PMC

Vukusic K, Thorsell A, Muslimovic A, Jonsson M, Dellgren G, Lindahl A, Sandstedt J, Hammarsten O. Overexpression of the SARS-CoV-2 receptor angiotensin converting enzyme 2 in cardiomyocytes of failing hearts. Sci Rep. 2022;12:965. doi: 10.1038/s41598-022-04956-y. PubMed DOI PMC

Nägele F, Graber M, Hirsch J, Pözl L, Sahanic S, Fiegl M, Hau D, et al. Correlation between structural heart disease and cardiac SARS-CoV-2 manifestations. Commun Med (Lond) 2022;2:142. doi: 10.1038/s43856-022-00204-6. PubMed DOI PMC

D’Onofrio N, Scisciola L, Sardu C, Trotta MC, De Feo M, Maiello C, Mascolo P, et al. Glycated ACE2 receptor in diabetes: Open door for SARS-COV-2 entry in cardiomyocyte. Cardiovasc Diabetol. 2021;20:99. doi: 10.1186/s12933-021-01286-7. PubMed DOI PMC

Chen J, Jiang Q, Xia X, Liu K, Yu Z, Tao W, Gong W, Han JJ. Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. Aging Cell. 2020;19:e13168. doi: 10.1111/acel.13168. PubMed DOI PMC

Schimmel L, Chew KY, Stocks CJ, Yordanov TE, Essebier P, Kulasinghe A, Monkman J, et al. Endothelial cells are not productively infected by SARS-CoV-2. Clin Transl Immunology. 2021;10:e1350. doi: 10.1002/cti2.1350. PubMed DOI PMC

Avdonin PP, Rybakova EY, Trufanov SK, Avdonin PV. SARS-CoV-2 receptors and their involvement in cell infection. Biochem (Mosc) Suppl Ser A Membr Cell Biol. 2023;17:1–11. doi: 10.1134/S1990747822060034. PubMed DOI PMC

Hou D, Cao W, Kim S, Cui X, Ziarnik M, Im W, Zhang XF. Biophysical investigation of interactions between SARS-CoV-2 spike protein and neuropilin-1. Protein Sci. 2023;32:e4773. doi: 10.1002/pro.4773. PubMed DOI PMC

Eberhardt N, Noval MG, Kaur R, Amadori L, Gildea M, Sajja S, Das D, et al. SARS-CoV-2 infection triggers pro-atherogenic inflammatory responses in human coronary vessels. Nat Cardiovasc Res. 2023;2:899–916. doi: 10.1038/s44161-023-00336-5. PubMed DOI PMC

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280.e278. doi: 10.1016/j.cell.2020.02.052. PubMed DOI PMC

Chong PY, Iqbal J, Yeong J, Aw TC, Chan KS, Chui PL. Immune response in myocardial injury: in situ hybridization and immunohistochemistry techniques for SARS-CoV-2 detection in COVID-19 autopsies. Front Mol Biosci. 2021;8:658932. doi: 10.3389/fmolb.2021.658932. PubMed DOI PMC

Wang XM, Mannan R, Xiao LB, Abdulfatah E, Qiao YY, Farver C, Myers JL, et al. Characterization of SARS-CoV-2 and host entry factors distribution in a COVID-19 autopsy series. Commun Med (Lond) 2021;1:24. doi: 10.1038/s43856-021-00025-z. PubMed DOI PMC

Wong DWL, Klinkhammer BM, Djudjaj S, Villwock S, Timm MC, Buhl EM, Wucherpfennig S, et al. Multisystemic cellular tropism of SARS-CoV-2 in autopsies of COVID-19 patients. Cells. 2021;10:1900. doi: 10.3390/cells10081900. PubMed DOI PMC

Sakamoto A, Kawakami R, Kawai K, Gianatti A, Pellegrini D, Kutys R, Guo L, et al. ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) expression and localization of SARS-CoV-2 infection in the human heart. Arterioscler Thromb Vasc Biol. 2021;41:542–544. doi: 10.1161/ATVBAHA.120.315229. PubMed DOI

Chen C, Wang J, Liu YM, Hu J. Single-cell analysis of adult human heart across healthy and cardiovascular disease patients reveals the cellular landscape underlying SARS-CoV-2 invasion of myocardial tissue through ACE2. J Transl Med. 2023;21:358. doi: 10.1186/s12967-023-04224-1. PubMed DOI PMC

Bozzo CP, Nchioua R, Volcic M, Koepke L, Krüger J, Schütz D, Heller S, et al. IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro. Nat Commun. 2021;12:4584. doi: 10.1038/s41467-021-24817-y. PubMed DOI PMC

Tang HT, Lu XS, Qie SY, Xi JN. Thoughts on detecting tissue distribution of potential COVID-19 receptors. Future Virol. 2020;15:489–496. doi: 10.2217/fvl-2020-0136. DOI

Ortega-Bernal D, Zarate S, Martinez-Cárdenas MD, Bojalil R. An approach to cellular tropism of SARS-CoV-2 through protein-protein interaction and enrichment analysis. Sci Rep. 2022;12:9399. doi: 10.1038/s41598-022-13625-z. PubMed DOI PMC

Adimulam T, Arumugam T, Gokul A, Ramsuran V. Genetic variants within SARS-CoV-2 human receptor genes may contribute to variable disease outcomes in different ethnicities. Int J Mol Sci. 2023;24:8711. doi: 10.3390/ijms24108711. PubMed DOI PMC

Dieter C, Brondani LD, Leitao CB, Gerchman F, Lemos NE, Crispim D. Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis. PLoS One. 2022;17:e0270627. doi: 10.1371/journal.pone.0270627. PubMed DOI PMC

Li J, Wang Y, Liu Y, Zhang Z, Zhai Y, Dai Y, Wu Z, Nie X, Du L. Polymorphisms and mutations of ACE2 and TMPRSS2 genes are associated with COVID-19: a systematic review. Eur J Med Res. 2022;27:26. doi: 10.1186/s40001-022-00647-6. PubMed DOI PMC

Pecoraro V, Cuccorese M, Trenti T. Genetic polymorphisms of ACE1, ACE2, IFTM3, TMPRSS2 and TNFα genes associated with susceptibility and severity of SARS-CoV-2 infection: a systematic review and meta-analysis. Clin Exp Med. 2023;23:3251–3264. doi: 10.1007/s10238-023-01038-9. PubMed DOI PMC

Strafella C, Caputo V, Termine A, Barati S, Gambardella S, Borgiani P, Caltagirone C, et al. Analysis of ACE2 genetic variability among populations highlights a possible link with COVID-19-related neurological complications. Genes (Basel) 2020;11:741. doi: 10.21203/rs.3.rs-28871/v1. PubMed DOI PMC

Posadas-Sánchez R, Fragoso JM, Sánchez-Muñoz F, Rojas-Velasco G, Ramírez-Bello J, López-Reyes A, Martínez-Gómez LE, et al. Association of the transmembrane serine protease-2 (TMPRSS2) polymorphisms with COVID-19. Viruses. 2022;14:1976. doi: 10.3390/v14091976. PubMed DOI PMC

Hamet P, Pausova Z, Attaoua R, Hishmih C, Haloui M, Shin J, Paus T, et al. SARS-CoV-2 receptor ACE2 gene is associated with hypertension and severity of COVID 19: Interaction with sex, obesity, and smoking. Am J Hypertens. 2021;34:367–376. doi: 10.1093/ajh/hpaa223. PubMed DOI PMC

Bulfamante GP, Perrucci GL, Falleni M, Sommariva E, Tosi D, Martinelli C, Songia P, et al. Evidence of SARS-CoV-2 transcriptional activity in cardiomyocytes of COVID-19 patients without clinical signs of cardiac involvement. Biomedicines. 2020;8:626. doi: 10.1101/2020.08.24.20170175. PubMed DOI PMC

Li X, Hu HR, Liu WL, Zhang QY, Wang YJ, Chen XJ, Zhu YP, et al. SARS-CoV-2-infected hiPSC-derived cardiomyocytes reveal dynamic changes in the COVID-19 hearts. Stem Cell Res Ther. 2023;14:361. doi: 10.1186/s13287-023-03603-1. PubMed DOI PMC

Bräuninger H, Stoffers B, Fitzek ADE, Meissner K, Aleshcheva G, Schweizer M, Weimann J, et al. Cardiac SARS-CoV-2 infection is associated with pro-inflammatory transcriptomic alterations within the heart. Cardiovasc Res. 2022;118:542–555. doi: 10.1093/cvr/cvab322. PubMed DOI PMC

Chang WT, Lin YW, Chen ZC, Liu PY. The S protein of SARS-CoV-2 injures cardiomyocytes indirectly through the release of cytokines instead of direct action. Acta Cardiol Sin. 2021;37:643–647. doi: 10.6515/ACS.202111_37(6).20210726B. PubMed DOI PMC

Yang LL, Han YL, Jaffré F, Nilsson-Payant BE, Bram Y, Wang PF, Zhu JJ, et al. An Immuno-cardiac model for macrophage-mediated inflammation in COVID-19 hearts. Circ Res. 2021;129:33–46. doi: 10.1161/CIRCRESAHA.121.319060. PubMed DOI PMC

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. PubMed DOI PMC

Alba JR, Zapater E, Martin C, Ocete D, Gonzalez-Cruz A, Angel-de-Miguel A, Ferrer C, Oishi N. Mapping of SARS-CoV-2 in Waldeyer’s lymphatic ring and visceral biopsies: the age and the illness duration’s impact. Braz J Otorhinolaryngol. 2023;89:101317. doi: 10.1016/j.bjorl.2023.101317. PubMed DOI PMC

Stein SR, Ramelli SC, Grazioli A, Chung JY, Singh M, Yinda CK, Winkler CW, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022;612:758–763. doi: 10.1038/s41586-022-05542-y. PubMed DOI PMC

Vymazalova K, Šerý O, Kralik P, Dziedzinska R, Musilova Z, Frishons J, Vojtisek T, Joukal M. Substantial decrease in SARS-CoV-2 RNA after fixation of cadavers intended for anatomical dissection. Anat Sci Int. 2023;98:441–447. doi: 10.1007/s12565-023-00707-9. PubMed DOI PMC

Kiseleva AA, Troisi EM, Hensley SE, Kohli RM, Epstein JA. SARS-CoV-2 spike protein binding selectively accelerates substrate-specific catalytic activity of ACE2. J Biochem. 2021;170:299–306. doi: 10.1093/jb/mvab041. PubMed DOI PMC

Chudasama YV, Zaccardi F, Gillies CL, Razieh C, Yates T, Kloecker DE, Rowlands AV, et al. Patterns of multimorbidity and risk of severe SARS-CoV-2 infection: an observational study in the UK. BMC Infect Dis. 2021;21:908. doi: 10.1186/s12879-021-06600-y. PubMed DOI PMC

Haslbauer JD, Tzankov A, Mertz KD, Schwab N, Nienhold R, Twerenbold R, Leibundgut G, et al. Characterisation of cardiac pathology in 23 autopsies of lethal COVID-19. J Pathol Clin Res. 2021;7:326–337. doi: 10.1002/cjp2.212. PubMed DOI PMC

Bansal M. Cardiovascular disease and COVID-19. Diabetes Metab Syndr. 2020;14:247–250. doi: 10.1016/j.dsx.2020.03.013. PubMed DOI PMC

Nassar Y, Mokhtar A, Elhadidy A, Elsayed M, Mostafa F, Rady A, Eladawy A, et al. Outcomes and risk factors for death in patients with coronavirus disease-2019 (COVID-19) pneumonia admitted to the intensive care units of an Egyptian University Hospital. A retrospective cohort study. J Infect Public Health. 2021;14:1381–1388. doi: 10.1016/j.jiph.2021.06.012. PubMed DOI PMC

Mitrofanova LB, Makarov IA, Gorshkov AN, Runov AL, Vonsky MS, Pisareva MM, Komissarov AB, et al. Comparative study of the myocardium of patients from four COVID-19 waves. Diagnostics (Basel) 2023;13:1645. doi: 10.3390/diagnostics13091645. PubMed DOI PMC

Greenwald MA, Namin S, Zajdowicz J, Jones AL, Fritts L, Kuehnert MJ, Miller CJ, Ray G. Testing of tissue specimens obtained from SARS-CoV-2 nasopharyngeal swab-positive donors. Cell Tissue Bank. 2024;25:583–604. doi: 10.1007/s10561-023-10119-8. PubMed DOI PMC

Reagan-Steiner S, Bhatnagar J, Martines RB, Milligan NS, Gisondo C, Williams FB, Lee E, et al. Detection of SARS-CoV-2 in neonatal autopsy tissues and placenta. Emerg Infect Dis. 2022;28:510–517. doi: 10.3201/eid2803.211735. PubMed DOI PMC

Falasca L, Nardacci R, Colombo D, Lalle E, Di Caro A, Nicastri E, Antinori A, et al. Postmortem findings in Italian patients with COVID-19: A descriptive full autopsy study of cases with and without comorbidities. J Infect Dis. 2020;222:1807–1815. doi: 10.1093/infdis/jiaa578. PubMed DOI PMC

Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, Thursz M, et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe. 2020;1:E245–E253. doi: 10.1016/S2666-5247(20)30115-4. PubMed DOI PMC

Remmelink M, De Mendonça R, D’Haene N, De Clercq S, Verocq C, Lebrun L, Lavis P, et al. Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care. 2020;24:495. doi: 10.1186/s13054-020-03218-5. PubMed DOI PMC

Tsatsakis A, Calina D, Falzone L, Petrakis D, Mitrut R, Siokas V, Pennisi M, et al. SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19. Food Chem Toxicol. 2020;146:111769. doi: 10.1016/j.fct.2020.111769. PubMed DOI PMC

Ishikura H, Maruyama J, Hoshino K, Matsuoka Y, Yano M, Arimura T, Katano H, et al. Coronavirus disease (COVID-19) associated delayed-onset fulminant myocarditis in patient with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. J Infect Chemother. 2021;27:1760–1764. doi: 10.1016/j.jiac.2021.08.007. PubMed DOI PMC

Marchiano S, Hsiang TY, Khanna A, Higashi T, Whitmore LS, Bargehr J, Davaapil H, et al. SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function. Stem Cell Reports. 2021;16:478–492. doi: 10.1016/j.stemcr.2021.02.008. PubMed DOI PMC

Yang YC, Wei ZY, Xiong CM, Qian HY. Direct mechanisms of SARS-CoV-2-induced cardiomyocyte damage: an update. Virol J. 2022;19:108. doi: 10.1186/s12985-022-01833-y. PubMed DOI PMC

Buchrieser J, Dufloo J, Hubert M, Monel B, Planas D, Rajah MM, Planchais C, et al. Syncytia formation by SARS-CoV-2-infected cells. EMBO J. 2020;39:e106267. doi: 10.15252/embj.2020106267. PubMed DOI PMC

Rajah MM, Bernier A, Buchrieser J, Schwartz O. The mechanism and consequences of SARS-CoV-2 spike-mediated fusion and syncytia formation. J Mol Biol. 2022;434:167280. doi: 10.1016/j.jmb.2021.167280. PubMed DOI PMC

Razaghi A, Szakos A, Al-Shakarji R, Björnstedt M, Szekely L. Morphological changes without histological myocarditis in hearts of COVID-19 deceased patients. Scand Cardiovasc J. 2022;56:166–173. doi: 10.1080/14017431.2022.2085320. PubMed DOI

Avolio E, Carrabba M, Milligan R, Williamson MK, Beltrami AP, Gupta K, Elvers KT, et al. The SARS-CoV-2 Spike protein disrupts human cardiac pericytes function through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease. Clin Sci (Lond) 2021;135:2668–2689. doi: 10.1042/CS20210735. PubMed DOI PMC

De Michele M, d’Amati G, Leopizzi M, Iacobucci M, Berto I, Lorenzano S, Mazzuti L, et al. Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients. J Hematol Oncol. 2022;15:108. doi: 10.1186/s13045-022-01329-w. PubMed DOI PMC

Mezache L, Nuovo GJ, Suster D, Tili E, Awad H, Radwanski PB, Veeraraghavan R. Histologic, viral, and molecular correlates of heart disease in fatal COVID-19. Ann Diagn Pathol. 2022;60:151983. doi: 10.1016/j.anndiagpath.2022.151983. PubMed DOI PMC

Cao X, Nguyen V, Tsai J, Gao C, Tian Y, Zhang Y, Carver W, et al. The SARS-CoV-2 spike protein induces long-term transcriptional perturbations of mitochondrial metabolic genes, causes cardiac fibrosis, and reduces myocardial contractile in obese mice. Mol Metab. 2023;74:101756. doi: 10.1016/j.molmet.2023.101756. PubMed DOI PMC

Huynh TV, Rethi L, Lee T-W, Higa S, Kao Y-H, Chen Y-J. Spike protein Impairs mitochondrial function in human cardiomyocytes: Mechanisms underlying cardiac injury in COVID-19. Cells. 2023;12:877. doi: 10.3390/cells12060877. PubMed DOI PMC

Fronza M, Thavendiranathan P, Chan V, Karur GR, Udell JA, Wald RM, Hong R, Hanneman K. Myocardial injury pattern at MRI in COVID-19 vaccine-associated myocarditis. Radiology. 2022;304:553–562. doi: 10.1148/radiol.212559. PubMed DOI PMC

Truong DT, Dionne A, Muniz JC, McHugh KE, Portman MA, Lambert LM, Thacker D, et al. Clinically suspected myocarditis temporally related to COVID-19 vaccination in adolescents and young adults: Suspected myocarditis after COVID-19 vaccination. Circulation. 2022;145:345–356. doi: 10.1161/CIRCULATIONAHA.121.056583. PubMed DOI

Nakahara T, Iwabuchi Y, Miyazawa R, Tonda K, Shiga T, Strauss HW, Antoniades C, Narula J, Jinzaki M. Assessment of myocardial (18)F-FDG uptake at PET/CT in asymptomatic SARS-CoV-2-vaccinated and nonvaccinated patients. Radiology. 2023;308:e230743. doi: 10.1148/radiol.230743. PubMed DOI

Zhou YB, Frey TK, Yang JJ. Viral calciomics: Interplays between Ca2+ and virus. Cell Calcium. 2009;46:1–17. doi: 10.1016/j.ceca.2009.05.005. PubMed DOI PMC

Wang WA, Carreras-Sureda A, Demaurex N. SARS-CoV-2 infection alkalinizes the ERGIC and lysosomes through the viroporin activity of the viral envelope protein. J Cell Sci. 2023;136:jcs260685. doi: 10.1242/jcs.260685. PubMed DOI PMC

Han Y, Zhu J, Yang L, Nilsson-Payant BE, Hurtado R, Lacko LA, Sun X, et al. SARS-CoV-2 infection induces ferroptosis of sinoatrial node pacemaker cells. Circ Res. 2022;130:963–977. doi: 10.1161/CIRCRESAHA.121.320518. PubMed DOI PMC

Chakraborty S, Chatterjee S, Mardi S, Mahata J, Kateriya S, Punnakkal P, Anirudhan G. COVID-19 ORF3a viroporin-influenced common and unique cellular signaling cascades in lung, heart, and the brain choroid plexus organoids with additional enriched microRNA network analyses for lung and the brain tissues. ACS Omega. 2023;8:45817–45833. doi: 10.1021/acsomega.3c06485. PubMed DOI PMC

Bois MC, Boire NA, Layman AJ, Aubry MC, Alexander MP, Roden AC, Hagen CE, et al. COVID-19-associated nonocclusive fibrin microthrombi in the heart. Circulation. 2021;143:230–243. doi: 10.1161/CIRCULATIONAHA.120.050754. PubMed DOI PMC

Kogan E, Berezovskiy Y, Blagova O, Kukleva A, Semyonova L, Gretsov E, Ergeshov A. Morphologically, immunohistochemically and PCR proven lymphocytic viral peri-, endo-, myocarditis in patients with fatal COVID-19. Diagn Pathol. 2022;17:31. doi: 10.1186/s13000-022-01207-6. PubMed DOI PMC

Duarte-Neto AN, Caldini EG, Gomes-Gouvêa MS, Kanamura CT, Monteiro RAD, Ferranti JF, Ventura AMC, et al. An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C. EClinicalMedicine. 2021;35:100850. doi: 10.1016/j.eclinm.2021.100850. PubMed DOI PMC

Bearse M, Hung YP, Krauson AJ, Bonanno L, Boyraz B, Harris CK, Helland TL, et al. Factors associated with myocardial SARS-CoV-2 infection, myocarditis, and cardiac inflammation in patients with COVID-19. Mod Pathol. 2021;34:1345–1357. doi: 10.1038/s41379-021-00790-1. PubMed DOI PMC

Egas D, Guadalupe JJ, Prado-Vivar B, Becerra-Wong M, Márquez S, Castillo S, Latta J, et al. SARS-CoV-2 detection and sequencing in heart tissue associated with myocarditis and persistent arrhythmia: A case report. IDCases. 2021;25:e01187. doi: 10.1016/j.idcr.2021.e01187. PubMed DOI PMC

Koskinas KC, Twerenbold R, Carballo D, Matter CM, Cook S, Heg D, Frenk A, et al. Effects of SARS-COV-2 infection on outcomes in patients hospitalized for acute cardiac conditions. A prospective, multicenter cohort study (Swiss Cardiovascular SARS-CoV-2 Consortium) Front Cardiovasc Med. 2023;10:1203427. doi: 10.3389/fcvm.2023.1203427. PubMed DOI PMC

Lira R, Luna-Rivero C, Morales-Bolaños FV, Sandoval-Gutiérrez JL, Moreno-Verduzco ER, Maldonado-Rodriguez A, Torres-Flores JM, Yocupicio-Monroy M, Sevilla-Reyes EE. Case report of a young adult with fatal COVID-19 and abundant SARS-CoV-2 nucleocapsid protein and lipofuscin accumulation in tissues. Heliyon. 2024;10:e23485. doi: 10.1016/j.heliyon.2023.e23485. PubMed DOI PMC

Wichmann D, Sperhake JP, Lügehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, et al. Autopsy findings and venous thromboembolism in patients with COVID-19. Ann Intern Med. 2020;173:268–277. doi: 10.7326/M20-2003. PubMed DOI PMC

Khismatullin RR, Ponomareva AA, Nagaswami C, Ivaeva RA, Montone KT, Weisel JW, Litvinov RI. Pathology of lung-specific thrombosis and inflammation in COVID-19. J Thromb Haemost. 2021;19:3062–3072. doi: 10.1111/jth.15532. PubMed DOI PMC

Cardona Buitrago C, Builes Gutierrez AM, Jimenez Marin D, Aristizabal Garcia C. Mechanical valve thrombosis secondary to severe acute respiratory syndrome Coronavirus 2 infection: A case report. Cureus. 2022;14:e23358. doi: 10.7759/cureus.23358. PubMed DOI PMC

McCrindle BW, Chasse M. Looking Backward and Forward: The Cardiovascular Complications of COVID-19. Can J Cardiol. 2023;39:710–712. doi: 10.1016/j.cjca.2023.04.006. PubMed DOI PMC

Ghantous E, Shetrit A, Hochstadt A, Banai A, Lupu L, Levi E, Szekely Y, et al. Cardiologic Manifestations in Omicron-Type Versus Wild-Type COVID-19: A Systematic Echocardiographic Study. J Am Heart Assoc. 2023;12:e027188. doi: 10.1161/JAHA.122.027188. PubMed DOI PMC

Yang CT, Liu F, Liu W, Cao GJ, Liu JC, Huang SJ, Zhu MX, et al. Myocardial injury and risk factors for mortality in patients with COVID-19 pneumonia. Int J Cardiol. 2021;326:230–236. doi: 10.1016/j.ijcard.2020.09.048. PubMed DOI PMC

Maheshwari A, Mahto D, Kumar V, Gulati S, Pemde H, Saha A, Mukherjee SB, et al. Comparison of clinical and laboratory profile of survivors and non-survivors of SARS-CoV-2-related multisystem inflammatory syndrome of childhood in India: An observational study. J Paediatr Child Health. 2022;58:136–140. doi: 10.1111/jpc.15675. PubMed DOI

Poe S, Vandivier-Pletsch RH, Clay M, Wong HR, Haynes E, Rothenberg FG. Cardiac troponin measurement in the critically Ill: Potential for guiding clinical management. J Investig Med. 2015;63:905–915. doi: 10.1097/JIM.0000000000000239. PubMed DOI PMC

Caforio AL, Brucato A, Doria A, Brambilla G, Angelini A, Ghirardello A, Bottaro S, et al. Anti-heart and anti-intercalated disk autoantibodies: evidence for autoimmunity in idiopathic recurrent acute pericarditis. Heart. 2010;96:779–784. doi: 10.1136/hrt.2009.187138. PubMed DOI

Caforio ALP, Re F, Avella A, Marcolongo R, Baratta P, Seguso M, Gallo N, et al. Evidence From family studies for autoimmunity in arrhythmogenic right ventricular cardiomyopathy: Associations of circulating anti-heart and anti-intercalated disk autoantibodies with disease severity and family history. Circulation. 2020;141:1238–1248. doi: 10.1161/CIRCULATIONAHA.119.043931. PubMed DOI

Escher F, Pietsch H, Aleshcheva G, Bock T, Baumeier C, Elsaesser A, Wenzel P, et al. Detection of viral SARS-CoV-2 genomes and histopathological changes in endomyocardial biopsies. Esc Heart Failure. 2020;7:2440–2447. doi: 10.1002/ehf2.12805. PubMed DOI PMC

Bürgi JJ, Rösslein M, Nolte O, Wick P, Boy RG, Stranders S, Dollenmaier G, et al. Mild COVID-19 induces early, quantifiable, persistent troponin I elevations in elder men. Front Cardiovasc Med. 2022;9:1053790. doi: 10.3389/fcvm.2022.1053790. PubMed DOI PMC

Alhindi T, Awad H, Alfaraj D, Salih SE, Abdelmoaty M, Muammar A. Troponin levels and the severity of COVID-19 pneumonia. Cureus. 2022;14:e23193. doi: 10.7759/cureus.23193. PubMed DOI PMC

Maggialetti N, Torrente A, Lazzari P, Villanova I, Marvulli P, Maresca R, Paparella C, et al. Coronary calcifications as a new prognostic marker in COVID-19 patients: role of CT. Eur Rev Med Pharmacol Sci. 2023;27:2173–2181. doi: 10.26355/eurrev_202303_31590. PubMed DOI

Blagova O, Lutokhina Y, Kogan E, Kukleva A, Ainetdinova D, Novosadov V, Rud R, et al. Chronic biopsy proven post-COVID myoendocarditis with SARS-Cov-2 persistence and high level of antiheart antibodies. Clin Cardiol. 2022;45:952–959. doi: 10.1002/clc.23886. PubMed DOI PMC

Makarov I, Mayrina S, Makarova T, Karonova T, Starshinova A, Kudlay D, Mitrofanova L. Morphological changes in the myocardium of patients with post-acute coronavirus syndrome: A study of endomyocardial biopsies. Diagnostics (Basel) 2023;13:2212. doi: 10.3390/diagnostics13132212. PubMed DOI PMC

The protective effect of serum antibodies in preventing SARS-CoV-2 virus entry into cardiac muscle