"Bonded by one chain, related to one purpose": what is primary in the development of thrombotic complications in COVID-19 — mechanisms of inflammation or endothelium damage?

Abstract

The ongoing COVID-19 pandemic has caused significant morbidity and mortality worldwide, as well as a profound impact on society. Among the nosologies that increase the risk of a severe course of COVID-19, coronary heart disease, chronic heart failure, cardiomyopathy. The main complications caused by coronavirus infection include thrombotic ones. Spike protein SARS-CoV-2 can interact directly with platelets and fibrin, causing blood hypercoagulation and obstructing blood flow. The presence of the spike protein in circulation leads to structural changes in fibrin, complement 3 and prothrombin, which can contribute to hypercoagulability in COVID-19 positive patients and cause a significant violation of fibrinolysis. Endothelial damage and systemic inflammation, being interrelated triggers of coagulopathy characteristic of COVID-19, trigger a cascade of reactions resulting in thrombotic complications against the background of endothelial dysfunction and hyperinflammation, which may be of clinical importance in the treatment of hypercoagulability in patients with COVID-19 (bibliography: 14 refs).

Keywords

endothelial dysfunction / new coronavirus infection / thrombosis

References

[1] Sergey Boytsov announced an increase in cases of late hospitalization for CVD by 25 %. Medvestnik. Available at: https://medvestnik.ru/content/news/Sergei-Boicov-zayavil-o-roste-sluchaev-pozdnei-gospitalizacii-po-povodu-SSZ-na-25.html (accessed 01.07.2021). (In Russ.)

[2] Сергей Бойцов заявил о росте случаев поздней госпитализации по поводу ССЗ на 25 % // Медвестник. Доступен по: https://medvestnik.ru/content/news/Sergei-Boicov-zayavil-o-roste-sluchaev-pozdnei-gospitalizacii-po-povodu-SSZ-na-25.html (дата обращения 01.07.2021).

[3] Kryukov EV, et al. Pathogenesis and clinical manifestations of cardiovascular lesions in patients with novel coronavirus infection (COVID-19). Saint Petersburg: S.M. Kirov Military Medical Academy Publishing House; 2021. 36 p. (In Russ.)

[4] Крюков Е.В. и др. Патогенез и клинические проявления поражения сердечно-сосудистой системы у пациентов с новой коронавирусной инфекцией (COVID-19). СПб.: Военно-медицинская академия им. С.М. Кирова, 2021. 36 с.

[5] 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: 10.1182/blood.2020006520

[6] Al-Samkari H., Karp Leaf R.S., Dzik W.H., et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection // Blood. 2020. Vol. 136, No. 4. P. 489–500. DOI:10.1182/blood.2020006520

[7] 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: 10.1055/s-0040-1710018

[8] 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. Vol. 120, No. 6. P. 998–1000. DOI:10.1055/s-0040-1710018

[9] 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: 10.1016/S0140-6736(20)30566-3

[10] 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. Vol. 395, Is. 10229. P. 1054–1062. DOI:10.1016/S0140-6736(20)30566-3

[11] 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. 2020;120(12):1720–1724. DOI: 10.1055/s-0040-1715835

[12] 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. Vol. 120, No. 12. P. 1720–1724. DOI: 10.1055/s-0040-1715835

[13] Cugno M, Meroni PL, Gualtierotti R, et al. Complement activation in patients with COVID-19: Anovel therapeutic target. J Allergy Clin Immunol. 2020;146(1):215–217. DOI: 10.1016/j.jaci.2020.05.006

[14] Cugno M., Meroni P.L., Gualtierotti R., et al. Complement activation in patients with COVID-19: Anovel therapeutic target // J. Allergy Clin. Immunol. 2020. Vol. 146, No. 1. P. 215–217. DOI:10.1016/j.jaci.2020.05.006

[15] Ip WK, Chan KH, Law HK, et al. Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection. J Infect Dis. 2005;191(10):1697–1704. DOI: 10.1086/429631

[16] Ip W.K., Chan K.H., Law H.K., et al. Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection // J. Infect. Dis. 2005. Vol. 191, No. 10. P. 1697–1704. DOI:10.1086/429631

[17] Mastellos DC, Ricklin D, Lambris JD. Clinical promise of next-generation complement therapeutics. Nat Rev Drug Discov. 2019;18(9):707–729. DOI: 10.1038/s41573-019-0031-6

[18] Mastellos D.C., Ricklin D., Lambris J.D. Clinical promise of next-generation complement therapeutics. Nat. Rev. Drug. Discov. 2019. Vol. 18, No. 9. P. 707–729. DOI:10.1038/s41573-019-0031-6

[19] Liu W, Li H. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Predprint. 2020. DOI: 10.26434/chemrxiv.11938173.v9

[20] Liu W., Li H. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism // ChemRxiv. Predprint. 2020. DOI: 10.26434/chemrxiv.11938173.v9

[21] Orlov YuP. Intravascular hemolysis of erythrocytes in the development of organ dysfunctions in critical conditions. Obshchaya reanimatologiya. 2008;6(2):88–94. (In Russ.) DOI: 10.15360/1813-9779-2008-2-88

[22] Орлов Ю.П. Внутрисосудистый гемолиз эритроцитов в развитии органных дисфункций при критических состояниях // Общая реаниматология. 2008. Т. 6, № 2. С. 88–94. DOI: 10.15360/1813-9779-2008-2-88

[23] Luzhnikov EA, ed. Medical toxicology. National guidelines. Moscow: GEOTAR-Media Publisher; 2014. 928 p. (In Russ.)

[24] Медицинская токсикология. Национальное руководство / под ред. Е.А. Лужниковa. М.; ГЭОТАР-Медиа, 2014. 928 с.

[25] 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: 10.38025/2078-1962-2020-97-3-25-30

[26] 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. T. 97, № 3. С. 25–30. DOI: 10.38025/2078-1962-2020-97-3-25-30

[27] Grobbelaar LM, Venter C, Vlok M, et al. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: Implications for microclot formation in COVID-19. medRxiv. Predprint. 2021. DOI: 10.1101/2021.03.05.21252960

[28] Grobbelaar L.M., Venter C., Vlok M., et al. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: Implications for microclot formation in COVID-19 // medRxiv. Predprint. 2021. (In Russ.) DOI: 10.1101/2021.03.05.21252960

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Cherkashin D.V.