Mechanisms of Damage to the Cardiovascular System in COVID-19

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Abstract

The review article is devoted to the analysis of the literature on the various mechanisms of damage to the cardiovascular system in COVID-19. The article briefly outlines the epidemiology and urgency of the COVID-19 problem, describes the features of the clinical picture of heart muscle damage in COVID-19. The pathophysiology, morphology and pathogenetic mechanisms of myocardial involvement in cases of SARS-CoV-2 lesion are considered in detail. The authors present a diagram of various mechanisms of myocardial damage in COVID-19, which includes mediated damage to the heart muscle through angiotensin-converting enzyme 2, myocardial damage caused by hypoxemia, microvascular heart damage, and systemic inflammatory response syndrome. A detailed scheme of cardiomyocyte infection with the involvement of cytokines, which ultimately leads to myocardial remodeling and dilated cardiomyopathy, is presented. The pathophysiological foundations of the development of sudden cardiac death in COVID-19, which include the mechanisms of life-threatening arrhythmias, acute coronary syndrome, and heart failure, are considered. The authors analyzed scientific studies of the toxic effects of COVID-19 drug treatment on the heart muscle, in particular, antiviral, antibacterial, antimalarial agents. Their potential benefits and harms, as well as the likelihood of developing cardiovascular events, in particular sudden cardiac death, were assessed.

About the authors

Alexandr Y. Fisun

Military Innovative Technopolis «ERA»

Email: era_1@mil.ru
SPIN-code: 9692-8019

MD, PhD, Professor, Corresponding Member of the RAS, Deputy Head

Russian Federation, 353456, Krasnodar region, Anapa, Pionersky pr., 41

Yuriy V. Lobzin

Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency

Email: niidi@niidi.ru
ORCID iD: 0000-0002-6934-2223
SPIN-code: 1172-3156

MD, PhD, Professor, academician of RAS, center president 

Russian Federation, 9, st. Professors Popov, St. Petersburg,197022

Dmitry V. Cherkashin

Military Medical Academy named after S.M. Kirov

Author for correspondence.
Email: cherkashin_dmitr@mail.ru
ORCID iD: 0000-0003-1363-6860
SPIN-code: 2781-9507

MD, PhD, Professor, Head of the Department and Clinic of Naval Therapy

Russian Federation, 6-A k. Lebedeva str., St. Petersburg, 194044

Vadim V. Tyrenko

Military Medical Academy named after S.M. Kirov

Email: vadim_tyrenko@mail.ru
ORCID iD: 0000-0002-0470-1109
SPIN-code: 3022-5038

MD, PhD, Head of the Department and Clinic of Faculty Therapy n.a. S.P. Botkin

Russian Federation, 6-A k. Lebedeva str., St. Petersburg, 194044

Konstantin N. Tkachenko

Military Medical Academy named after S.M. Kirov

Email: constantt@rambler.ru
ORCID iD: 0000-0002-3432-0278
SPIN-code: 7098-4783

MD, PhD, Lecturer at the Department of Naval Therapy

Russian Federation, 6-A k. Lebedeva str., St. Petersburg, 194044

Vasilii A. Kachnov

Military Medical Academy named after S.M. Kirov

Email: kvasa@mail.ru
ORCID iD: 0000-0002-6601-5366
SPIN-code: 2084-0290

MD, PhD, doctoral student at the Department of Faculty Therapy

Russian Federation, 6-A k. Lebedeva str., St. Petersburg, 194044

Gennadiy G. Kutelev

Military Medical Academy named after S.M. Kirov

Email: kutelev@mail.ru
ORCID iD: 0000-0002-6489-9938
SPIN-code: 5139-8511

MD, PhD, doctoral student at the Department of Naval Therapy

Russian Federation, 6-A k. Lebedeva str., St. Petersburg, 194044

Ignat V. Rudchenko

Military Innovative Technopolis «ERA»

Email: ignatrudchenko@mail.ru
ORCID iD: 0000-0001-7737-3604
SPIN-code: 8918-5849

MD, PhD, Head of the Laboratory of Biotechnical Systems and Technologies

Russian Federation, 353456, Krasnodar region, Anapa, Pionersky pr., 41

Alexey D. Sobolev

Military Medical Academy named after S.M. Kirov

Email: sobolevvmeda@rambler.ru
ORCID iD: 0000-0002-8085-5425
SPIN-code: 3831-6584

Adjunct at the Department of Naval Therapy

Russian Federation, 6-A k. Lebedeva str., St. Petersburg, 194044

References

  1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020;91(1):157–160. doi: https://doi.org/10.23750/abm.v91i1.9397
  2. COVID-19 Map. Johns Hopkins Coronavirus Resource Center. Accessed October 13, 2020. Available from: https://coronavirus.jhu.edu/map.html
  3. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. 2020;5(7):831–840. doi: https://doi.org/10.1001/jamacardio.2020.1286
  4. 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: https://doi.org/10.1161/CIRCULATIONAHA.120.0475491
  5. Inciardi RM, Lupi L, Zaccone G, et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):819–824. doi: https://doi.org/10.1001/jamacardio.2020.1096
  6. 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: https://doi.org/10.1001/jamacardio.2020.0950
  7. 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: https://doi.org/10.1161/CIRCULATIONAHA.120.047008
  8. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi: https://doi.org/10.1016/S0140-6736(20)30183-5
  9. Alhogbani T. Acute myocarditis associated with novel Middle East respiratory syndrome coronavirus. Ann Saudi Med. 2016;36(1):78–80. doi: https://doi.org/10.5144/0256-4947.2016.78
  10. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069. doi: https://doi.org/10.1001/jama.2020.1585
  11. Tsui K-L, Leung T-C, Yam LY-C, et al. Coronary plague instability in severe acute respiratory syndrome. Int J Cardiol. 2005;99(3):471–472. doi: https://doi.org/10.1016/j.ijcard.2003.11.052
  12. Liu Y, Li J, Feng Y. Critical care response to a hospital outbreak of the 2019-nCoV infection in Shenzhen, China. Crit Care. 2020;24(1):56. doi: https://doi.org/10.1186/s13054-020-2786-x
  13. Zhou Y, Fu B, Zheng X, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev. 2020;7(6):998–1002. doi: https://doi.org/10.1093/nsr/nwaa041
  14. South AM, Diz DI, Chappell MC. COVID-19, ACE2, and the cardiovascular consequences. American Journal of Physiology-Heart and Circulatory Physiology. 2020;318(5):H1084–H1090. doi: https://doi.org/10.1152/ajpheart.00217.2020
  15. Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020;58(7):1116–1120. doi: https://doi.org/10.1515/cclm-2020-0188
  16. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–1418. doi: https://doi.org/10.1016/S0140-6736(20)30937-5
  17. Donoghue M, Hsieh F, Baronas E, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87(5):E1-9. doi: https://doi.org/10.1161/01.res.87.5.e1
  18. Ou X, Liu Y, Lei X, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620. doi: https://doi.org/10.1038/s41467-020-15562-9
  19. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483): 1260–1263. doi: https://doi.org/10.1126/science.abb2507
  20. Kim J, Choi SM, Lee J, et al. Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study. Korean J Crit Care Med. 2017;32(2):154–163. doi: https://doi.org/10.4266/kjccm.2016.00976
  21. Фисун А.Я., Черкашин Д.В., Тыренко В.В., и др. Роль ренин-ангиотензин-альдостероновой системы во взаимодействии с коронавирусом SARS-CoV-2 и в развитии стратегий профилактики и лечения новой коронавирусной инфекции (COVID-19) // Артериальная гипертензия. — 2020. — Т. 26. — № 3. — С. 248–262. [Fisun AYa, Cherkashin DV, Tyrenko VV, et al. Role of renin-angiotensin-aldosterone system in the interaction with coronavirus SARS-CoV-2 and in the development of strategies for prevention and treatment of new coronavirus infection (COVID-19). Arterial Hypertension. 2020;26(3):248–262. (In Russ.)] doi: https://doi.org/10.18705/1607-419X-2020-26-3-248-262
  22. Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003;289(21):2801–2809. doi: https://doi.org/10.1001/jama.289.21.JOC30885
  23. Oudit GY, Kassiri Z, Jiang C, et al. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest. 2009;39(7):618–625. doi: https://doi.org/10.1111/j.1365-2362.2009.02153.x
  24. Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients with Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671–1681. doi: https://doi.org/10.1161/CIRCRESAHA.120.317134
  25. Sala S, Peretto G, Gramegna M, et al. Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection. Eur Heart J. Published online April 8, 2020. doi: https://doi.org/10.1093/eurheartj/ehaa286
  26. 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: https://doi.org/10.1002/ejhf.1828
  27. Yao XH, Li TY, He ZC, et al. A pathological report of three COVID-19 cases by minimal invasive autopsies. Zhonghua Bing Li Xue Za Zhi. 2020;49(5):411–417. doi: https://doi.org/10.3760/cma.j.cn112151-20200312-00193
  28. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–422. doi: https://doi.org/10.1016/S2213-2600(20)30076-X
  29. Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol. 1987;18(6):619–624. doi: https://doi.org/10.1016/s0046-8177(87)80363-5
  30. Fung G, Luo H, Qiu Y, Yang D, McManus B. Myocarditis. Circ Res. 2016;118(3):496–514. doi: https://doi.org/10.1161/CIRCRESAHA.115.306573
  31. Akhmerov A, Marbán E. COVID-19 and the Heart. Circ Res. 2020;126(10):1443–1455. doi: https://doi.org/10.1161/CIRCRESAHA.120.317055
  32. Kim I-C, Kim JY, Kim HA, Han S. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J. Published online April 13, 2020. doi: https://doi.org/10.1093/eurheartj/ehaa288
  33. Wei X, Fang Y, Hu H. Glucocorticoid and immunoglobulin to treat viral fulminant myocarditis. Eur Heart J. 2020;41(22):2122. doi: https://doi.org/10.1093/eurheartj/ehaa357
  34. Hua A, O’Gallagher K, Sado D, Byrne J. Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19. Eur Heart J. 2020;41(22):2130. doi: https://doi.org/10.1093/eurheartj/ehaa253
  35. Laureti M, Narayanan D, Rodriguez-Andres J, et al. Flavivirus Receptors: Diversity, Identity, and Cell Entry. Front Immunol. 2018;9:2180. doi: https://doi.org/10.3389/fimmu.2018.02180
  36. Mazzon M, Marsh M. Targeting viral entry as a strategy for broad-spectrum antivirals. F1000Res. 2019;8. doi: https://doi.org/10.12688/f1000research.19694.1
  37. Millet JK, Whittaker GR. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proc Natl Acad Sci USA. 2014;111(42):15214–15219. doi: https://doi.org/10.1073/pnas.1407087111
  38. White JM, Delos SE, Brecher M, Schornberg K. Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme. Crit Rev Biochem Mol Biol. 2008;43(3):189–219. doi: https://doi.org/10.1080/10409230802058320
  39. Thorley JA, McKeating JA, Rappoport JZ. Mechanisms of viral entry: sneaking in the front door. Protoplasma. 2010;244(1–4):15–24. doi: https://doi.org/10.1007/s00709-010-0152-6
  40. Sun X, Wang T, Cai D, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev. 2020;53:38–42. doi: https://doi.org/10.1016/j.cytogfr.2020.04.002
  41. Behrens EM, Koretzky GA. Review: Cytokine Storm Syndrome: Looking Toward the Precision Medicine Era. Arthritis Rheumatol. 2017;69(6):1135–1143. doi: https://doi.org/10.1002/art.40071
  42. Chau VQ, Oliveros E, Mahmood K, et al. The Imperfect Cytokine Storm. JACC Case Rep. 2020;2(9):1315–1320. doi: https://doi.org/10.1016/j.jaccas.2020.04.001
  43. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. Accessed October 13, 2020. Available from: https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance
  44. Liu K, Fang Y-Y, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl). 2020;133(9):1025–1031. doi: https://doi.org/10.1097/CM9.0000000000000744
  45. Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic. J Am Coll Cardiol. 2020;75(18):2352–2371. doi: https://doi.org/10.1016/j.jacc.2020.03.031
  46. Giudicessi JR, Roden DM, Wilde AAM, Ackerman MJ. Genetic susceptibility for COVID-19 — associated sudden cardiac death in African Americans. Heart Rhythm. 2020;17(9):1487–1492. doi: https://doi.org/10.1016/j.hrthm.2020.04.045
  47. Lazzerini PE, Boutjdir M, Capecchi PL. COVID-19, Arrhythmic Risk, and Inflammation: Mind the Gap! Circulation. 2020;142(1):7–9. doi: https://doi.org/10.1161/CIRCULATIONAHA.120.047293
  48. 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. Lancet. 2020;395(10229):1054–1062. doi: https://doi.org/10.1016/S0140-6736(20)30566-3
  49. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–1034. doi: https://doi.org/10.1016/S0140-6736(20)30628-0
  50. Временные методические рекомендации «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19) (версия 10 от 08.02.2021)» [Электронный ресурс]. Available from: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/054/588/original/Временные_МР_COVID-19_%28v.10%29-08.02.2021_%281%29.pdf
  51. Руководство по диагностике и лечению болезней системы кровообращения в контексте пандемии COVID-19 [Электронный ресурс]. Available from: https://russjcardiol.elpub.ru/jour/article/view/3801 (дата обращения: 13.10.2020).
  52. CredibleMeds: Home. Accessed October 13, 2020. Available from: https://www.crediblemeds.org/
  53. Jankelson L, Karam G, Becker ML, et al. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020;17(9):1472–1479. doi: https://doi.org/10.1016/j.hrthm.2020.05.008
  54. Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19). Mayo Clin Proc. 2020;95(6):1213–1221. doi: https://doi.org/10.1016/j.mayocp.2020.03.024
  55. Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489–500. doi: https://doi.org/10.1182/blood.2020006520
  56. Spiezia L, Boscolo A, Poletto F, et al. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure. Thromb Haemost. 2020;120(6):998–1000. doi: https://doi.org/10.1055/s-0040-1710018
  57. Eriksson O, Hultström M, Persson B, et al. Mannose-Binding Lectin is Associated with Thrombosis and Coagulopathy in Critically Ill COVID-19 Patients. Thromb Haemost. Published online September 1, 2020. doi: https://doi.org/10.1055/s-0040-1715835
  58. Cugno M, Meroni PL, Gualtierotti R, et al. Complement activation in patients with COVID-19: A novel therapeutic target. J Allergy Clin Immunol. 2020;146(1):215–217. doi: https://doi.org/10.1016/j.jaci.2020.05.006
  59. Ip WKE, Chan KH, Law HKW, et al. Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection. J Infect Dis. 2005;191(10):1697–1704. doi: https://doi.org/10.1086/429631
  60. Mastellos DC, Ricklin D, Lambris JD. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov. 2019;18(9):707–729. doi: https://doi.org/10.1038/s41573-019-0031-6
  61. Wenzhong L, Hualan L. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. Published online July 13, 2020. doi: https://doi.org/10.26434/chemrxiv.11938173.v9
  62. Орлов Ю.П. Патогенетическая значимость нарушенного обмена железа при критических состояниях: автореф. ... д-ра мед. наук. — Омск, 2009. — 43 с. [Orlov YuP. Patogeneticheskaya znachimost’ narushennogo obmena zheleza pri kriticheskih sostoyaniyah: avtoref. ... d-ra med. nauk. Omsk; 2009. 43 р. (In Russ.)]
  63. Хоффман Р.С., Хауланд М., Нельсон Л. Экстренная медицинская помощь при отравлениях: пер. с англ. — М.: Практика, 2010. — 1440 с. [Hoffman RS, Howland M, Nelson L. Emergency medical care for poisoning. Moscow: Praktika; 2010. 1440 p.]
  64. Медицинская токсикология: Национальное руководство / под ред. Е.А. Лужников. — М.: ГЕОТАР-Медиа, 2014. — 928 с. [Medicinskaya toksikologiya: Nacional’noe rukovodstvo / pod red. E.A. Luzhnikov. Moscow: GEOTAR-Media; 2014. 928 p. (In Russ.)]
  65. Лодягин А.Н. Батоцыренов Б.В., Шикалова И.А., Вознюк И.А. Ацидоз и токсический гемолиз — цели патогенетического лечения полиорганной патологии при COVID-19 // Вестник восстановительной медицины. — 2020. — Т. 97. — № 3. — С. 25–30. [Lodyagin AN, Batotsyrenov BV, Shikalova IA, Voznyuk IA. Acidosis and toxic hemolysis — goals of pathogenetic treatment of polyorgan pathology in Covid-19. Bulletin of Rehabilitation Medicine. 2020;97(3):25–30. (In Russ.)] doi: https://doi.org/10.38025/ 2078-1962-2020-97-3-25-30
  66. Foy BH, Carlson JCT, Reinertsen E, et al. Association of Red Blood Cell Distribution WIDTH with Mortality Risk in Hospitalized Adults with SARS-CoV-2 Infection. JAMA Netw Open. 2020;3(9). doi: https://doi.org/10.1001/jamanetworkopen.2020.22058
  67. Rubin EJ, Harrington DP, Hogan JW, Gatsonis C, Baden LR, Hamel MB. The Urgency of Care during the Covid-19 Pandemic — Learning as We Go. N Engl J Med. Published online May 7, 2020. doi: https://doi.org/10.1056/NEJMe2015903
  68. McCreary EK, Pogue JM. Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options. Open Forum Infect Dis. 2020;7(4). doi: https://doi.org/10.1093/ofid/ofaa105
  69. Smit C, Peeters MYM, van den Anker JN, Knibbe CAJ. Chloroquine for SARS-CoV-2: Implications of Its Unique Pharmacokinetic and Safety Properties. Clin Pharmacokinet. 2020;59(6):659–669. doi: https://doi.org/10.1007/s40262-020-00891-1
  70. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. Published online May 22, 2020. doi: https://doi.org/10.1016/S0140-6736(20)31180-6
  71. Jaffe S. Regulators split on antimalarials for COVID-19. Lancet. 2020;395(10231):1179. doi: https://doi.org/10.1016/S0140-6736(20)30817-5
  72. fda.gov [Internet]. FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. FDA. Published online June 26, 2020. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or (аccessed: 13.10.2020).
  73. Ektorp E. Death threats after a trial on chloroquine for COVID-19. Lancet Infect Dis. 2020;20(6):661. doi: https://doi.org/10.1016/S1473-3099(20)30383-2
  74. COVID-19 Scientific and Public Health Policy Update — 28 April 2020. Africa CDC. Accessed October 13, 2020. Available from: https://africacdc.org/download/covid-19-scientific-and-public-health-policy-update-28-april-2020/
  75. Baralić K, Jorgovanović D, Živančević K, et al. Safety assessment of drug combinations used in COVID-19 treatment: in silico toxicogenomic data-mining approach. Toxicology and Applied Pharmacology. 2020;406:115237. doi: https://doi.org/10.1016/j.taap.2020.115237.

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2. Fig. 1. Scheme of the ways of influence on the cardiovascular system of SARS-CoV-2 when an infected person enters the body

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3. Fig. 2. Possible scheme of various mechanisms of myocardial damage in SARS-CoV-2

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4. Fig. 3. Scheme of cardiomyocyte infection

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5. Fig. 4. Sudden cardiac death and fatal arrhythmias from SARS-CoV-2 infection

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

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2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».