sechenovSechenov Medical JournalСеченовский вестник2218-73322658-3348Сеченовский Университет10.47093/2218-7332.2020.11.2.50-61sechenov-241Research ArticleCOVID-19COVID-19Complex mechanism of COVID-19 developmentКомплексный механизм развития СOVID-19https://orcid.org/0000-0002-1574-477XБолевичС. Б.BolevichS. B.

Болевич Сергей Бранкович, д-р мед. наук, профессор, заведующий кафедрой патологии человека 

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119991

+7 (926) 371-89-93

Sergey B. Bolevich, MD, PhD, DMSc, Professor, Head of the Human Pathology Department

8/2, Trubetskaya str., Moscow, 119991

bolevich2011@yandex.ruhttps://orcid.org/0000-0002-5794-9263БолевичC. C.BolevichS. S.

Болевич Стефани Сергеевна, ассистент кафедры патофизиологии 

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119991

Stefani S. Bolevich, Assistant Professor, Pathophysiology Department

8/2, Trubetskaya str., Moscow, 119991

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation202006122020112Special Issue: COVID-195061Copyright © Bolevich S.B., Bolevich S.S., 20202020Болевич С.Б., Болевич C.C.Bolevich S.B., Bolevich S.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sechenovmedj.com/jour/article/view/241

Coronavirus infection (COVID-19) is an acute viral disease, which affects all vital organs and is caused by an RNA-genomic virus of the genus Betacoronavirus of the family Coronaviridae. This virus (SARS-CoV-2) enters the body through the respiratory tract and interacts primarily with Toll-like receptors of epithelial cells of the bronchi, alveoli, intestines and vascular endotheliocytes, as well as with angiotensin-converting enzyme 2 receptors. Toll-like receptors activate nuclear factor Kappa B in these cells, which initiates the formation of many cytokines (“cytokine storm”). SARS-CoV-2 affects type II pneumocytes by causing a termination of surfactant formation and, accordingly, alveolar shrinking and the formation of acute respiratory distress syndrome and also fibrosis on the interalveolar-capillary membrane and the formation of acute respiratory failure. SARS-CoV-2 and cytokines disrupt the function of vascular endothelial cells, which leads to endothelial dysfunction. In microvessels forms a mass formation of microthrombi, which causes the failure of organs and systems. “Cytokine storm” turns into cytokine sepsis with the formation of multiple organ dysfunction syndrome.

Коронавирусная инфекция (COVID-19) — острое вирусное заболевание с поражением всех жизненно важных органов, вызываемое РНК-геномным вирусом рода Betacoronavirus семейства Coronaviridae. SARS-CoV-2 попадает в организм через дыхательные пути и взаимодействует в первую очередь с Толл-рецепторами (TLR) эпителиальных клеток бронхов, альвеол, кишечника и эндотелиоцитов сосудов, а также с рецепторами ангиотензинпревращающего фермента 2. TLR активируют в данных клетках ядерный фактор каппа В (NF-κB), который, в свою очередь, инициирует образование в большом количестве цитокинов («цитокиновая буря»). SARS-CoV-2, поражая пневмоциты II типа, вызывает прекращение образования сурфактанта и, соответственно, сморщивание альвеол и возникновение острого респираторного дистресс-синдрома, а также образование фиброза на альвеолярно-капиллярной мембране и возникновение острой дыхательной недостаточности. SARS-CoV-2 и цитокины нарушают функцию эндотелиальных клеток сосудов, что приводит к возникновению эндотелиальной дисфункции. В микрососудах происходит массовое образование микротромбов, что вызывает нарушение функции органов и систем. «Цитокиновая буря» переходит в цитокиновый сепсис с возникновением синдрома полиорганной недостаточности.

COVID-19SARS-CoV-2коронавирусная инфекцияцитокиныострый респираторный дистресссиндромэндотелиальная дисфункцияCOVID-19SARS-CoV-2corona virus infectioncytokineacute respiratory distress syndromeendothelial dysfunctionReferencesZheng M., Gao Y., Wang G., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May; 17(5): 533–5. https://doi.org/10.1038/s41423-020-0402-2 PMID: 32203188Zheng M., Gao Y., Wang G., et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020 May; 17(5): 533–5. https://doi.org/10.1038/s41423-020-0402-2 PMID: 32203188Li Q., Guan X., Wu P., et al. Early transmission dynamics in Wuhan, China, of Novel Coronavirus-infected pneumonia. N Engl J Med. 2020 Mar 26; 382(13): 1199–207. https://doi.org/10.1056/NEJMoa2001316 PMID: 31995857Li Q., Guan X., Wu P., et al. Early transmission dynamics in Wuhan, China, of Novel Coronavirus-infected pneumonia. N Engl J Med. 2020 Mar 26; 382(13): 1199–207. https://doi.org/10.1056/NEJMoa2001316 PMID: 31995857Wan Y., Shang J., Graham R., et al. Receptor recognition by novel coronavirus from Wuhan: an Analysis based on decade-long structural studies of SARS. J Virol. 2020 Mar 17; 94(7): e00127–20. https://doi.org/10.1128/JVI.00127-20 PMID: 31996437Wan Y., Shang J., Graham R., et al. Receptor recognition by novel coronavirus from Wuhan: an Analysis based on decade-long structural studies of SARS. J Virol. 2020 Mar 17; 94(7): e00127–20. https://doi.org/10.1128/JVI.00127-20 PMID: 31996437Xiao L., Sakagami H., Miwa N. ACE2: The key molecule for understanding the pathophysiology of severe and critical conditions of COVID-19: Demon or Angel? Viruses. 2020 Apr 28; 12(5): 491. https://doi.org/10.3390/v12050491 PMID: 32354022Xiao L., Sakagami H., Miwa N. ACE2: The key molecule for understanding the pathophysiology of severe and critical conditions of COVID-19: Demon or Angel? Viruses. 2020 Apr 28; 12(5): 491. https://doi.org/10.3390/v12050491 PMID: 32354022Chen Y., Guo Y., Pan Y., et al. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020 Feb 17; 525(1): 135–40. https://doi.org/10.1016/j.bbrc.2020.02.071 PMID: 32081428Chen Y., Guo Y., Pan Y., et al. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020 Feb 17; 525(1): 135–40. https://doi.org/10.1016/j.bbrc.2020.02.071 PMID: 32081428Ziegler C., Allon A.S., Nyquist S.K., et al. SARS-CoV-2 Receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is enriched in specific cell subsets across tissues. Cell. 2020 May 28; 181(5): 1016–35.e19. https://doi.org/10.1016/j.cell.2020.04.035 PMID: 32413319Ziegler C., Allon A.S., Nyquist S.K., et al. SARS-CoV-2 Receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is enriched in specific cell subsets across tissues. Cell. 2020 May 28; 181(5): 1016–35.e19. https://doi.org/10.1016/j.cell.2020.04.035 PMID: 32413319Yuki K., Fujiogi M., Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020 Jun; 8. Zou X., Chen K., 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 Apr; 14(2): 185–92. https://doi/org/10.1007/s11684-020-0754-0 PMID: 32170560Yuki K., Fujiogi M., Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020 Jun; 8. Zou X., Chen K., 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 Apr; 14(2): 185–92. https://doi/org/10.1007/s11684-020-0754-0 PMID: 32170560Zhou P., Yang X.L., Wang X.G., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar; 579(7798): 270–3. https://doi/org/10.1038/s41586-020-2012-7 PMID: 32015507Zhou P., Yang X.L., Wang X.G., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar; 579(7798): 270–3. https://doi/org/10.1038/s41586-020-2012-7 PMID: 32015507Walls A.C., Park Y.J., Tortorici M.A., et al. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell. 2020 Apr 16; 181(2): 281–92.e6. https://doi.org/10.1016/j.cell.2020.02.058 PMID: 32155444Walls A.C., Park Y.J., Tortorici M.A., et al. Structure, function, and antigenicity of the SARS-CoV-2 Spike glycoprotein. Cell. 2020 Apr 16; 181(2): 281–92.e6. https://doi.org/10.1016/j.cell.2020.02.058 PMID: 32155444Anand P., Puranik M., Aravamudan М., et al. SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. Elife. 2020 May 26; 9: e58603. https://doi.org/10.7554/eLife.58603 PMID: 32452762Anand P., Puranik M., Aravamudan М., et al. SARS-CoV-2 strategically mimics proteolytic activation of human ENaC. Elife. 2020 May 26; 9: e58603. https://doi.org/10.7554/eLife.58603 PMID: 32452762Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. 2020 Apr 7; 323(13): 1239–42. https://doi.org/10.1001/jama.2020.2648 PMID: 32091533Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese center for disease control and prevention. JAMA. 2020 Apr 7; 323(13): 1239–42. https://doi.org/10.1001/jama.2020.2648 PMID: 32091533Wu J., Wu X., Zeng W., et al. Chest CT Findings in patients with corona virus disease 2019 and its relationship with clinical features. Invest Radiol. 2020 May; 55(5): 257–61. https://doi.org/10.1097/RLI.0000000000000670 PMID: 32091414Wu J., Wu X., Zeng W., et al. Chest CT Findings in patients with corona virus disease 2019 and its relationship with clinical features. Invest Radiol. 2020 May; 55(5): 257–61. https://doi.org/10.1097/RLI.0000000000000670 PMID: 32091414Zhang S., Li H., Huang S., et al. High-resolution CT features of 17 cases of corona virus disease 2019 in Sichuan province, China. Eur Respir J. 2020 Apr 30; 55(4): 2000334. https://doi.org/10.1183/13993003.00334-2020 PMID: 32139463Zhang S., Li H., Huang S., et al. High-resolution CT features of 17 cases of corona virus disease 2019 in Sichuan province, China. Eur Respir J. 2020 Apr 30; 55(4): 2000334. https://doi.org/10.1183/13993003.00334-2020 PMID: 32139463Qian Z., Travanty E.A., Oko L., et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. 2013; 48(6): 742–8. https://doi/org/10.1165/rcmb.2012-0339OC PMID: 23418343Qian Z., Travanty E.A., Oko L., et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am J Respir Cell Mol Biol. 2013; 48(6): 742–8. https://doi/org/10.1165/rcmb.2012-0339OC PMID: 23418343Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr; 8(4): 420–2. https://doi/org/10.1016/S2213-2600(20)30076-X PMID: 32085846Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr; 8(4): 420–2. https://doi/org/10.1016/S2213-2600(20)30076-X PMID: 32085846Newton A.H., Cardani A., Braciale T.J. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol. 2016; 38(4): 471–82. https://doi/org/10.1007/s00281-016-0558-0 PMID: 26965109Newton A.H., Cardani A., Braciale T.J. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol. 2016; 38(4): 471–82. https://doi/org/10.1007/s00281-016-0558-0 PMID: 26965109Liu Y., Yang Y., Zhang C., et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020 Mar; 63(3): 364–74. https://doi.org/10.1007/s11427-020-1643-8 PMID: 32048163Liu Y., Yang Y., Zhang C., et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020 Mar; 63(3): 364–74. https://doi.org/10.1007/s11427-020-1643-8 PMID: 32048163Genschmer K.R., Russell D.W., Lal C., et al. Activated PMN exosomes: pathogenic entities causing matrix destruction and disease in the lung. Cell. 2019 Jan 10; 176(1–2): 113–26.e15. https://doi.org/10.1016/j.cell.2018.12.002 PMID: 30633902Genschmer K.R., Russell D.W., Lal C., et al. Activated PMN exosomes: pathogenic entities causing matrix destruction and disease in the lung. Cell. 2019 Jan 10; 176(1–2): 113–26.e15. https://doi.org/10.1016/j.cell.2018.12.002 PMID: 30633902Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15; 395(10223): 497–506. https://doi/org/10.1016/S0140-6736(20)30183-5 PMID: 31986264Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15; 395(10223): 497–506. https://doi/org/10.1016/S0140-6736(20)30183-5 PMID: 31986264He F., Deng Y., Li W. Coronavirus disease 2019: What we know? J Med Virol. 2020 Mar; 92(7): 719–25. https://doi/org/10.1002/jmv.25766 PMID: 32170865He F., Deng Y., Li W. Coronavirus disease 2019: What we know? J Med Virol. 2020 Mar; 92(7): 719–25. https://doi/org/10.1002/jmv.25766 PMID: 32170865Liu J., Zheng X., Tong Q., et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020 May; 92(5): 491–4. https://doi.org/10.1002/jmv.25709 PMID: 32056249Liu J., Zheng X., Tong Q., et al. Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV. J Med Virol. 2020 May; 92(5): 491–4. https://doi.org/10.1002/jmv.25709 PMID: 32056249Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr; 8(4): 420–2. https://doi.org/10.1016/S2213-2600(20)30076-X PMID: 32085846Xu Z., Shi L., Wang Y., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr; 8(4): 420–2. https://doi.org/10.1016/S2213-2600(20)30076-X PMID: 32085846Ruan Q., Yang K., Wang W., et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May; 46(5): 846–8. https://doi.org/10.1007/s00134-020-05991-x PMID: 32125452Ruan Q., Yang K., Wang W., et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May; 46(5): 846–8. https://doi.org/10.1007/s00134-020-05991-x PMID: 32125452Wang D., Hu B., Hu C., et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Mar 17; 323(11): 1061–9. https://doi.org/10.1001/jama.2020.1585 PMID: 32031570Wang D., Hu B., Hu C., et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020 Mar 17; 323(11): 1061–9. https://doi.org/10.1001/jama.2020.1585 PMID: 32031570Kuster G.M., Pfister O., Burkard T., et al. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19? Eur Heart J. 2020 May 14; 41(19): 1801–3. https://doi.org/10.1093/eurheartj/ehaa235 PMID: 32196087Kuster G.M., Pfister O., Burkard T., et al. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19? Eur Heart J. 2020 May 14; 41(19): 1801–3. https://doi.org/10.1093/eurheartj/ehaa235 PMID: 32196087Bell T.J., Brand O.J., Morgan D.J., et al. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biol. 2019 Jul; 80: 14–28. https://doi.org/10.1016/j.matbio.2018.06.006 PMID: 2993304Bell T.J., Brand O.J., Morgan D.J., et al. Defective lung function following influenza virus is due to prolonged, reversible hyaluronan synthesis. Matrix Biol. 2019 Jul; 80: 14–28. https://doi.org/10.1016/j.matbio.2018.06.006 PMID: 2993304Heldin P., Lin C.Y., Kolliopoulos C., et al. Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production. Matrix Biol. 2019 May; 78–9: 100–17. https://doi.org/10.1016/j.matbio.2018.01.017 PMID: 29374576Heldin P., Lin C.Y., Kolliopoulos C., et al. Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production. Matrix Biol. 2019 May; 78–9: 100–17. https://doi.org/10.1016/j.matbio.2018.01.017 PMID: 29374576van den Brand J.M.A., Haagmans B.L., van Riel D., et al. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J Comp Pathol. 2014 Jul; 151(1): 83–112. https://doi.org/10.1016/j.jcpa.2014.01.004 PMID: 24581932van den Brand J.M.A., Haagmans B.L., van Riel D., et al. The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models. J Comp Pathol. 2014 Jul; 151(1): 83–112. https://doi.org/10.1016/j.jcpa.2014.01.004 PMID: 24581932Lin C.W., Lin K.H., Hsieh T.H., et al. Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunol Med Microbiol. 2006 Apr; 46(3): 375–80. https://doi.org/10.1111/j.1574-695X.2006.00045.x PMID: 16553810Lin C.W., Lin K.H., Hsieh T.H., et al. Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunol Med Microbiol. 2006 Apr; 46(3): 375–80. https://doi.org/10.1111/j.1574-695X.2006.00045.x PMID: 16553810Khomich O.A., Kochetkov S.N., Bartosch B., et al. Redox biology of respiratory viral infections. Viruses. 2018 Jul 26; 10(8): 392. https://doi.org/10.3390/v10080392 PMID: 30049972Khomich O.A., Kochetkov S.N., Bartosch B., et al. Redox biology of respiratory viral infections. Viruses. 2018 Jul 26; 10(8): 392. https://doi.org/10.3390/v10080392 PMID: 30049972Imai Y., Kuba K., Neely G.G., et al. Identification of Oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008 Apr 18; 133(2): 235–49. https://doi.org/10.1016/j.cell.2008.02.043 PMID: 18423196Imai Y., Kuba K., Neely G.G., et al. Identification of Oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 2008 Apr 18; 133(2): 235–49. https://doi.org/10.1016/j.cell.2008.02.043 PMID: 18423196Gambardella J., Sardu C., Santulli G., et al. Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020 May 11; 9(5): 1417. https://doi.org/10.3390/jcm9051417 PMID: 32403217Gambardella J., Sardu C., Santulli G., et al. Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? A comprehensive evaluation of clinical and basic evidence. J Clin Med. 2020 May 11; 9(5): 1417. https://doi.org/10.3390/jcm9051417 PMID: 32403217Escher R., Breakey N., Lammle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020 Jun; 190: 62. https://doi.org/ 10.1016/j.thromres.2020.04.014 PMID: 32305740Escher R., Breakey N., Lammle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020 Jun; 190: 62. https://doi.org/ 10.1016/j.thromres.2020.04.014 PMID: 32305740Schiffrin E.L., Flack J., Ito S., et al. Hypertension and COVID-19. Am J Hypertens. 2020 Apr 6; 33(5): 373–4. https://doi.org/10.1093/ajh/hpaa057 PMID: 32251498Schiffrin E.L., Flack J., Ito S., et al. Hypertension and COVID-19. Am J Hypertens. 2020 Apr 6; 33(5): 373–4. https://doi.org/10.1093/ajh/hpaa057 PMID: 32251498Richardson S., Hirsch J.S., Narasimhan M. The Northwell COVID-19 research consortium. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA. 2020 May 26; 323(20): 2052–9. https://doi.org/10.1001/jama.2020.6775 PMID: 32320003Richardson S., Hirsch J.S., Narasimhan M. The Northwell COVID-19 research consortium. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA. 2020 May 26; 323(20): 2052–9. https://doi.org/10.1001/jama.2020.6775 PMID: 32320003Chen T., Wu D., Chen H., et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 2020 Mar 26; 368: m1091. https://doi.org/10.1136/bmj.m1091 PMID: 32217556Chen T., Wu D., Chen H., et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: Retrospective study. BMJ. 2020 Mar 26; 368: m1091. https://doi.org/10.1136/bmj.m1091 PMID: 32217556Myers L.C., Parodi S.M., Escobar G.J., Liu V.X. Characteristics of hospitalized adults with COVID-19 in an integrated health care system in California. JAMA. 2020 Jun 2; 323(21): 2195–8. https://doi/org/10.1001/jama.2020.7202 PMID:32329797Myers L.C., Parodi S.M., Escobar G.J., Liu V.X. Characteristics of hospitalized adults with COVID-19 in an integrated health care system in California. JAMA. 2020 Jun 2; 323(21): 2195–8. https://doi/org/10.1001/jama.2020.7202 PMID:32329797Guan W.J., Liang W.H., Zhao Y., et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. Eur Respir J. 2020 May 14; 55(5): 2000547. https://doi.org/10.1183/13993003.00547-2020 PMID: 32217650Guan W.J., Liang W.H., Zhao Y., et al. Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. Eur Respir J. 2020 May 14; 55(5): 2000547. https://doi.org/10.1183/13993003.00547-2020 PMID: 32217650Zhou 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 Mar 28; 395(10229): 1054–62. https://doi.org./10.1016/S0140-6736(20)30566-3 PMID: 32171076Zhou 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 Mar 28; 395(10229): 1054–62. https://doi.org./10.1016/S0140-6736(20)30566-3 PMID: 32171076Bikdeli B., Madhavan M.V., Jimenez D., et al. Lip GYH. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020 Jun 16; 75(23): 2950–73. https://doi/org/10.1016/j.jacc.2020.04.031 PMID: 32311448Bikdeli B., Madhavan M.V., Jimenez D., et al. Lip GYH. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020 Jun 16; 75(23): 2950–73. https://doi/org/10.1016/j.jacc.2020.04.031 PMID: 32311448Klok F.A., Kruip M., van der Meer N.J.M., et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul; 191: 145–7. https://doi/org 10.1016/j.thromres.2020.04.013 PMID: 32291094Klok F.A., Kruip M., van der Meer N.J.M., et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020 Jul; 191: 145–7. https://doi/org 10.1016/j.thromres.2020.04.013 PMID: 32291094Durvasula R., Wellington T., McNamara E., et al. COVID-19 and kidney failure in the acute care setting: our experience from Seattle. Am J Kidney Dis. 2020 Jul; 76(1): 4–6. https://doi.org/10.1053/j.ajkd.2020.04.001 PMID: 32276031Durvasula R., Wellington T., McNamara E., et al. COVID-19 and kidney failure in the acute care setting: our experience from Seattle. Am J Kidney Dis. 2020 Jul; 76(1): 4–6. https://doi.org/10.1053/j.ajkd.2020.04.001 PMID: 32276031Ronco C., Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol. 2020 Jun; 16(6): 308–10. https://doi.org/10.1038/s41581-020-0284-7 PMID: 32273593Ronco C., Reis T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol. 2020 Jun; 16(6): 308–10. https://doi.org/10.1038/s41581-020-0284-7 PMID: 32273593Rotzinger D.C., Beigelman-Aubry C., von Garnier C., Qanadli S.D. Pulmonary embolism in patients with COVID-19: Time to change the paradigm of computed tomography. Thromb Res. 2020 Jun; 190: 58–9. htpps://doi/org/10.1016/j.thromres.2020.04.011 PMID: 32302782Rotzinger D.C., Beigelman-Aubry C., von Garnier C., Qanadli S.D. Pulmonary embolism in patients with COVID-19: Time to change the paradigm of computed tomography. Thromb Res. 2020 Jun; 190: 58–9. htpps://doi/org/10.1016/j.thromres.2020.04.011 PMID: 32302782Poissy J., Goutay J., Caplan M., et al. Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence. Circulation. 2020 Jul 14; 142(2): 184–6. https://doi/org/10.1161/CIRCULATIONAHA.120.047430 PMID: 32330083Poissy J., Goutay J., Caplan M., et al. Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence. Circulation. 2020 Jul 14; 142(2): 184–6. https://doi/org/10.1161/CIRCULATIONAHA.120.047430 PMID: 32330083Aggarwal G., Lippi G., Michael Henry B. Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019 (COVID-19): A pooled analysis of published literature. Int J Stroke. 2020 Jun; 15(4): 385–9. https://doi.org/10.1177/1747493020921664 PMID: 32310015Aggarwal G., Lippi G., Michael Henry B. Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019 (COVID-19): A pooled analysis of published literature. Int J Stroke. 2020 Jun; 15(4): 385–9. https://doi.org/10.1177/1747493020921664 PMID: 32310015Mao L., Jin H., Wang M., et al. Neurologic Manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1; 77(6): 683–90. https://doi/org/10.1001/jamaneurol.2020.1127 PMID: 32275288Mao L., Jin H., Wang M., et al. Neurologic Manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020 Jun 1; 77(6): 683–90. https://doi/org/10.1001/jamaneurol.2020.1127 PMID: 32275288Riphagen S., Gomez R., Gonzalez-Martinez C., et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020, in press. 2020 May 23; 395(10237): 1607–8. https://doi/org/10.1016/S0140-6736(20)31094-1 PMID: 32386565Riphagen S., Gomez R., Gonzalez-Martinez C., et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020, in press. 2020 May 23; 395(10237): 1607–8. https://doi/org/10.1016/S0140-6736(20)31094-1 PMID: 32386565Lovren F., Pan Y., Quan A., et al. Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Am J Physiol Heart Circ Physiol. 2008 Oct; 295(4): H1377–84. https://doi.org/10.1152/ajpheart.00331.2008 PMID: 18660448Lovren F., Pan Y., Quan A., et al. Angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis. Am J Physiol Heart Circ Physiol. 2008 Oct; 295(4): H1377–84. https://doi.org/10.1152/ajpheart.00331.2008 PMID: 18660448Vanarsdall A.L., Pritchard S.R., Wisner T.W. CD147 Promotes entry of pentamer-expressing human cytomegalovirus into epithelial and endothelial cells. mBio. 2018 May 8; 9(3): e00781–18. https://doi.org./10.1128/mBio.00781-18 PMID: 29739904Vanarsdall A.L., Pritchard S.R., Wisner T.W. CD147 Promotes entry of pentamer-expressing human cytomegalovirus into epithelial and endothelial cells. mBio. 2018 May 8; 9(3): e00781–18. https://doi.org./10.1128/mBio.00781-18 PMID: 29739904Zhang M.D., Xiao M., Zhang S., et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med. 2020 Apr 23; 382(17): e38. https://doi.org./10.1056/NEJMc2007575 PMID: 32268022Zhang M.D., Xiao M., Zhang S., et al. Coagulopathy and antiphospholipid antibodies in patients with Covid-19. N Engl J Med. 2020 Apr 23; 382(17): e38. https://doi.org./10.1056/NEJMc2007575 PMID: 32268022Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr; 18(4): 844–7. https://doi.org/10.1111/jth.14768 PMID: 32073213Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr; 18(4): 844–7. https://doi.org/10.1111/jth.14768 PMID: 32073213Lin L., Lu L., Cao W., Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec; 9(1): 727–32. htps://doi.org/10.1080/22221751.2020.1746199 PMID: 32196410Lin L., Lu L., Cao W., Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020 Dec; 9(1): 727–32. htps://doi.org/10.1080/22221751.2020.1746199 PMID: 32196410Iba T., Levy J.H., Warkentin T.E., et al. Scientific, Standardization committee on DIC, the S, Standardization Committee on P, Critical Care of the International Society on T and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019 Nov; 17(11): 1989–94. https://doi.org/10.1111/jth.14578 PMID:31410983Iba T., Levy J.H., Warkentin T.E., et al. Scientific, Standardization committee on DIC, the S, Standardization Committee on P, Critical Care of the International Society on T and Haemostasis. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost. 2019 Nov; 17(11): 1989–94. https://doi.org/10.1111/jth.14578 PMID:31410983Abret N., Britton G.J., Gruber C., et al. The Sinai immunology review project. Immunology of COVID-19: Current state of the science. Immunity. 2020 Jun 16; 52(6): 910–41. https://doi.org/10.1016/j.immuni.2020.05.002 PMID: 32505227Abret N., Britton G.J., Gruber C., et al. The Sinai immunology review project. Immunology of COVID-19: Current state of the science. Immunity. 2020 Jun 16; 52(6): 910–41. https://doi.org/10.1016/j.immuni.2020.05.002 PMID: 32505227de Wit E., van Doremalen N., Falzarano D., Munster V.J. SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug; 14(8): 523–34. https://doi.org/10.1038/nrmicro.2016.81 PMID: 27344959de Wit E., van Doremalen N., Falzarano D., Munster V.J. SARS and MERS: Recent insights into emerging coronaviruses. Nat Rev Microbiol. 2016 Aug; 14(8): 523–34. https://doi.org/10.1038/nrmicro.2016.81 PMID: 27344959Ishiguro T., Matsuo K., Fujii S., Takayanagi N. Acute thrombotic vascular events complicating influenza-associated pneumonia. Respir Med Case Rep. 2019 Jun 14; 28: 100884. https://doi.org/10.1016/j.rmcr.2019.100884 PMID: 31245274Ishiguro T., Matsuo K., Fujii S., Takayanagi N. Acute thrombotic vascular events complicating influenza-associated pneumonia. Respir Med Case Rep. 2019 Jun 14; 28: 100884. https://doi.org/10.1016/j.rmcr.2019.100884 PMID: 31245274Risitano A.M., Mastellos D.C., Huber-Lang M., et al. Complement as a target in COVID-19? Nat Rev Immunol. 2020 Jun; 20(6): 343–4. https://doi.org/10.1038/s41577-020-0320-7 PMID: 32327719Risitano A.M., Mastellos D.C., Huber-Lang M., et al. Complement as a target in COVID-19? Nat Rev Immunol. 2020 Jun; 20(6): 343–4. https://doi.org/10.1038/s41577-020-0320-7 PMID: 32327719

The authors declare that there are no conflicts of interest present.