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Clinical, morphological and molecular biological examination of the myocardium in COVID-19 patients

https://doi.org/10.15829/1560-4071-2022-4810

Abstract

The presence of coronavirus-associated myocarditis remains controversial despite elevations in cardiac troponin and natriuretic peptide in many patients.

Aim. To assess the morphological changes in the myocardium of patients who died due to coronavirus disease 2019 (COVID-19) and compare them with the intravital level of cardiac biomarkers.

Material and methods. A total of 420 hospital charts and 77 autopsies of those who died from COVID-19 were analyzed. In 15 of 77 cases (19%) with histologically suspected myocarditis, an immunohistochemical examination of the myocardium with antibodies to CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, VP1 of enteroviruses was performed, and in 8 patients with immunohistochemically confirmed myocarditis (10%) — polymerase chain reaction for SARS-CoV-2.

Results. Hemorrhage, intramural thrombosis, necrosis of non-coronary origin, myocardial infarction and lymphocytic myocarditis were detected in 43%, 10%, 17%, 19% and 10% of cases, respectively, without coronavirus N and E gene sequences in the myocardium. Dysplasia, hyperplasia and hypertrophy of the vascular endothelium, expression of Ang1, VWF, VEGF, MHC1, C1q, VP1 of enteroviruses were determined in 100, 100, 87, 100, 75 and 62% of cases of myocarditis, respectively. There were no significant correlations between inflammatory biomarkers and myocarditis.

Conclusion. The main morphological manifestation of COVID-19 in the myocardium is the so-called endotheliitis with dysplasia and endothelial activation, leading to hemorrhages, intramural thrombosis and necrosis. There is no convincing evidence of a direct involvement of coronavirus in myocarditis induction.

About the Authors

L. B. Mitrofanova
Almazov National Medical Research Center
Russian Federation

St. Petersburg


Competing Interests:

none



I. A. Makarov
Almazov National Medical Research Center
Russian Federation

St. Petersburg


Competing Interests:

none



A. L. Runov
Almazov National Medical Research Center; D.I. Mendeleev Institute for Metrology
Russian Federation

St. Petersburg


Competing Interests:

none



M. S. Vonsky
Almazov National Medical Research Center; D.I. Mendeleev Institute for Metrology
Russian Federation

St. Petersburg


Competing Interests:

none



I. A. Danilova
Almazov National Medical Research Center
Russian Federation

St. Petersburg


Competing Interests:

none



V. S. Sidorin
Almazov National Medical Research Center
Russian Federation

St. Petersburg


Competing Interests:

none



O. M. Moiseva
Almazov National Medical Research Center
Russian Federation

St. Petersburg


Competing Interests:

none



A. O. Conradi
Almazov National Medical Research Center
Russian Federation

St. Petersburg


Competing Interests:

none



References

1. Bularga A, Chapman AR, Mills NL. Mechanisms of Myocardial Injury in COVID-19. Clin Chem. 2021;67(8):1044-1046. doi: 10.1093/clinchem/hvab111.

2. European Society of Cardiology. ESC Guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic. Last updated June 2020. https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance

3. Chapman AR, Bularga A, Mills NL. High-Sensitivity Cardiac Troponin Can Be an Ally in the Fight Against COVID-19. Circulation. 2020;141(22):1733-1735. doi: 10.1161/CIRCULATIONAHA.120.047008

4. Friedrich MG, Cooper LT. What we (don't) know about myocardial injury after COVID-19. Eur Heart J. 2021;42(19):1879-1882. doi: 10.1093/eurheartj/ehab145.

5. Weckbach LT, Curta A, Bieber S, et al. Myocardial Inflammation and Dysfunction in COVID-19-Associated Myocardial Injury. Circ Cardiovasc Imaging. 2021;14(1):e012220. doi: 10.1161/CIRCIMAGING.120.011713.

6. Suo T, Liu X, Feng J, et al. ddPCR: a more accurate tool for SARS-CoV-2 detection in low viral load specimens. Emerg Microbes Infect. 2020;9(1):1259-1268. doi: 10.1080/22221751.2020.1772678.

7. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045. doi: 10.2807/1560-7917.ES.2020.25.3.2000045.

8. Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol. 2007;50(19):1914-31. doi: 10.1016/j.jacc.2007.09.008. PMID: 17980265.

9. BIPM. National Measurement Institutes demonstrate high accuracy reference measurement system for SARS-CoV-2 testing. https://www.bipm.org/en/-/2020-nmi-covid (15.11.2021)

10. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418. doi: 10.1016/S0140-6736(20)30937-5.

11. Gheblawi M, Wang K, Viveiros A, et al. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circ Res. 2020;126(10):1456-1474. doi: 10.1161/CIRCRESAHA.120.317015.

12. Liu PP, Blet A, Smyth D, Li H. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulation. 2020;142(1):68-78. doi: 10.1161/CIRCULATIONAHA.120.047549.

13. 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(7):802-810. doi: 10.1001/jamacardio.2020.0950.

14. 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. doi: 10.1002/ejhf.1828.

15. Wenzel P, Kopp S, Göbel S, Jet 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. doi: 10.1093/cvr/cvaa160.

16. Kim IC, Kim JY, Kim HA, et al. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J. 2020;41(19):1859. doi: 10.1093/eurheartj/ehaa288.

17. 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. doi: 10.1002/ejhf.1828.

18. Giustino G, Pinney SP, Lala A, et al. Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar. J Am Coll Cardiol. 2020;76(17):2011-2023. doi: 10.1016/j.jacc.2020.08.059.

19. 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. doi: 10.1001/jamacardio.2020.3551.

20. Andréoletti L, Bourlet T, Moukassa D, et al. Enteroviruses can persist with or without active viral replication in cardiac tissue of patients with end-stage ischemic or dilated cardiomyopathy. J Infect Dis. 2000;182(4):1222-7. doi: 10.1086/315818.

21. Marjomäki V, Kalander K, Hellman M, et al. Enteroviruses and coronaviruses: similarities and therapeutic targets. Expert Opin Ther Targets. 2021;25(6):479-489. doi: 10.1080/14728222.2021.1952985.

22. Weckbach LT, Curta A, Bieber S, et al. Myocardial Inflammation and Dysfunction in COVID-19-Associated Myocardial Injury. Circ Cardiovasc Imaging. 2021;14(1):e012220. doi: 10.1161/CIRCIMAGING.120.011713.

23. Scott AJ, O'Dea KP, O'Callaghan D, et al. Reactive oxygen species and p38 mitogen-activated protein kinase mediate tumor necrosis factor α-converting enzyme (TACE/ADAM-17) activation in primary human monocytes. J Biol Chem. 2011;286(41):35466-35476. doi: 10.1074/jbc.M111.277434.

24. Basso C, Leone O, Rizzo S, et al. Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study. Eur Heart J. 2020;41(39):3827-3835. doi: 10.1093/eurheartj/ehaa664.

25. Fox SE, Li G, Akmatbekov A, et al. Unexpected Features of Cardiac Pathology in COVID-19 Infection. Circulation. 2020;142(11):1123-1125. doi: 10.1161/CIRCULATIONAHA.120.049465.

26. Tao Z, Chen B, Tan X, et al. Coexpression of VEGF and angiopoietin-1 promotes angiogenesis and cardiomyocyte proliferation reduces apoptosis in porcine myocardial infarction (MI) heart. Proc Natl Acad Sci U S A. 2011;108(5):2064-9. doi: 10.1073/pnas.1018925108.

27. Dallabrida SM, Ismail N, Oberle JR, et al. Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins. Circ Res. 2005;96(4):e8-24. doi: 10.1161/01.RES.0000158285.57191.60.

28. Ray PS, Estrada-Hernandez T, Sasaki H, et al. Early effects of hypoxia/reoxygenation on VEGF, ang-1, ang-2 and their receptors in the rat myocardium: implications for myocardial angiogenesis. Mol Cell Biochem. 2000;213(1-2):145-53. doi: 10.1023/a:1007180518474.

29. Mojiri A, Alavi P, Lorenzana Carrillo MA, et al. Endothelial cells of different organs exhibit heterogeneity in von Willebrand factor expression in response to hypoxia. Atherosclerosis. 2019;282:1-10. doi: 10.1016/j.atherosclerosis.2019.01.002.

30. Spiel AO, Gilbert JC, Jilma B. von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation. 2008;117(11):1449-59. doi: 10.1161/CIRCULATIONAHA.107.722827.

31. Witsch T, Martinod K, Sorvillo N, et al. Recombinant Human ADAMTS13 Treatment Improves Myocardial Remodeling and Functionality After Pressure Overload Injury in Mice. J Am Heart Assoc. 2018;7(3):e007004. doi: 10.1161/JAHA.117.007004.

32. Smeeth L, Thomas SL, Hall AJ, et al. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351(25):2611-8. doi: 10.1056/NEJMoa041747.

33. Hirsch JS, Ng JH, Ross DW, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98(1):209-218. doi: 10.1016/j.kint.2020.05.006.

34. Bonow RO, Fonarow GC, O'Gara PT, et al. Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality. JAMA Cardiol. 2020;5(7):751-753. doi: 10.1001/jamacardio.2020.1105.

35. Blanco-Melo D, Nilsson-Payant BE, Liu WC, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020;181(5):1036-1045.e9. doi: 10.1016/j.cell.2020.04.026.


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Mitrofanova L.B., Makarov I.A., Runov A.L., Vonsky M.S., Danilova I.A., Sidorin V.S., Moiseva O.M., Conradi A.O. Clinical, morphological and molecular biological examination of the myocardium in COVID-19 patients. Russian Journal of Cardiology. 2022;27(7):4810. (In Russ.) https://doi.org/10.15829/1560-4071-2022-4810

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ISSN 1560-4071 (Print)
ISSN 2618-7620 (Online)