Pathophysiology of Cardiovascular Complications in COVID-19

Vladimir Petrovic, Dina Radenkovic, Goran Radenkovic, Vukica Djordjevic, Maciej Banach, Vladimir Petrovic, Dina Radenkovic, Goran Radenkovic, Vukica Djordjevic, Maciej Banach

Abstract

Numerous recent studies have shown that patients with underlying cardiovascular disease (CVD) are at increased risk of more severe clinical course as well as mortality of COVID-19. Also, the available data suggests that COVID-19 is related to numerous de novo cardiovascular complications especially in the older population and those with pre-existing chronic cardiometabolic conditions. SARS-CoV-2 virus can cause acute cardiovascular injury, as well as increase the risk of chronic cardiovascular damage. As CVD seem to be the major comorbidity in critically unwell patients with COVID-19 and patients often die of cardiovascular complications, we review the literature and discuss the possible pathophysiology and molecular pathways driving these disease processes: cytokine release syndrome, RAAS system dysregulation, plaque destabilization and coagulation disorders with the aim to identify novel treatment targets. In addition, we review the pediatric population, the major cause of the cardiovascular complications is pediatric inflammatory multisystem syndrome that is believed to be associated with COVID-19 infection. Due to the increasingly recognized CVD damage in COVID-19, there is a need to establish clear clinical and follow-up protocols and to identify and treat possible comorbidities that may be risk factors for the development of cardiovascular complications.

Keywords: COVID-19; CVD; Pediatric Inflammatory Multisystem Syndrome; cytokine release syndrome; thrombosis.

Copyright © 2020 Petrovic, Radenkovic, Radenkovic, Djordjevic and Banach.

Figures

FIGURE 1
FIGURE 1
The pathogenesis mechanisms of cardiovascular complications in COVID-19. (A) Cytokine release syndrome (“cytokine storm”) is a systemic inflammatory response that plays the crucial role in the development of cardiovascular complications; (B) The downregulation of ACE2 receptors; (C) Plaque destabilization can lead to the plaque rupture and consequent formation of microthrombi; (D) Coagulation disorders contribute to the cloth formation and microthrombosis in different organs.

References

    1. Arnett D. K., Blumenthal R. S., Albert M. A., Buroker A. B., Goldberger Z. D., Hahn E. J., et al. (2019). 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation 140 596–646.
    1. Bahrami A., Parsamanesh N., Atkin S. L., Banach M., Sahebkar A. (2018). Effect of statins on toll-like receptors: a new insight to pleiotropic effects. Pharmacol. Res. 135 230–238. 10.1016/j.phrs.2018.08.014
    1. Banach M., Penson P. E., Fras Z., Vrablik M., Pella D., Reiner Ž, et al. (2020). Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic. Pharmacol. Res. 158:104891. 10.1016/j.phrs.2020.104891
    1. Basu-Ray I., Almaddah N. K., Adeboye A., Soos M. P. (2020). Cardiac Manifestations Of Coronavirus (COVID-19). Treasure Island, FL: StatPearls Publishing.
    1. Bavishi C., Bonow R. O., Trivedi V., Abbott J. D., Messerli F. H., Bhatt D. L. (2020). Acute myocardial injury in patients hospitalized with COVID-19 infection: a review. Prog. Cardiovasc. Dis. 10.1016/j.pcad.2020.05.013 [Epub ahead of print].
    1. Bertram S., Heurich A., Lavender H., Gierer S., Danisch S., Perin P., et al. (2012). Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts. PLoS One 7:e35876. 10.1371/journal.pone.0035876
    1. Bitker L., Burrell L. M. (2019). Classic and nonclassic renin-angiotensin systems in the critically Ill. Crit. Care Clin. 35 213–227. 10.1016/j.ccc.2018.11.002
    1. Bowles L., Platton S., Yartey N., Dave M., Lee K., Hart D. P., et al. (2020). Lupus anticoagulant and abnormal coagulation tests in patients with COVID-19. N. Engl. J. Med. 383 288–290. 10.1056/NEJMc2013656
    1. Bukowska A., Spiller L., Wolke C., Lendeckel U., Weinert S., Hoffmann J., et al. (2017). Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men. Exp. Biol. Med. 242 1412–1423. 10.1177/1535370217718808
    1. Cao X. (2020). COVID-19: immunopathology and its implications for therapy. Nat. Rev. Immunol. 20 269–270. 10.1038/s41577-020-0308-3
    1. Chang J. C. (2019). Sepsis and septic shock: endothelial molecular pathogenesis associated with vascular microthrombotic disease. Thromb J. 17:10. 10.1186/s12959-019-0198-4
    1. Chang Y. S., Ko B. H., Ju J. C., Chang H. H., Huang S. H., Lin C. W. (2020). SARS unique domain (SUD) of severe acute respiratory syndrome coronavirus induces NLRP3 inflammasome-dependent CXCL10-mediated pulmonary inflammation. Int. J. Mol. Sci. 21:3179. 10.3390/ijms21093179
    1. Channappanavar R., Fehr A. R., Vijay R., Mack M., Zhao J., Meyerholz D. K. (2016). Dysregulated Type I Interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe 19 181–193. 10.1016/j.chom.2016.01.007
    1. Chatenoud L., Ferran C., Legendre C., Thouard I., Merite S., Reuter A., et al. (1990). In vivo cell activation following OKT3 administration. Systemic cytokine release and modulation by corticosteroids. Transplantation 49 697–702. 10.1097/00007890-199004000-00009
    1. Chen J., Zhang Z. Z., Chen Y. K., Long Q. X., Tian W. G., Deng H. J., et al. (2020). The clinical and immunological features of pediatric COVID-19 patients in China. Genes Dis. 10.1016/j.gendis.2020.03.008 [Epub ahead of print].
    1. Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., et al. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395 507–513. 10.1016/S0140-6736(20)30211-7
    1. Cheung E. W., Zachariah P., Gorelik M., Boneparth A., Kernie S. G., Orange J. S., et al. (2020). Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York city. JAMA 324 294–296. 10.1001/jama.2020.10374
    1. Connors J. M., Levy J. H. (2020). COVID-19 and its implications for thrombosis and anticoagulation. Blood 135 2033–2040. 10.1182/blood.2020006000
    1. Crackower M. A., Sarao R., Oudit G. Y., Yagil C., Kozieradzki I., Scanga S. E., et al. (2002). Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417 822–828. 10.1038/nature00786
    1. Der Sarkissian S., Grobe J. L., Yuan L., Narielwala D. R., Walter G. A., Katovich M. J., et al. (2008). Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology. Hypertension 51 712–718. 10.1161/HYPERTENSIONAHA.107.100693
    1. Dolinski D., Dolinska B., Zmaczynska-Witek B., Banach M., Kulesza W. (2020). Unrealistic optimism in the time of coronavirus pandemic: may it help to kill, if so-whom: disease or the person? J. Clin. Med. 9:E1464. 10.3390/jcm9051464
    1. Dong N., Cai J., Zhou Y., Liu J., Li F. (2020). End-stage heart failure with COVID-19. strong evidence of myocardial injury by 2019-nCoV. JACC Heart Fail. 8 515–517. 10.1016/j.jchf.2020.04.001
    1. Driggin E., Madhavan M. V., Bikdeli B., Chuich T., Laracy J., Biondi-Zoccai G. (2020). Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J. Am. Coll. Cardiol. 75 2352–2371.
    1. Emami A., Javanmardi F., Pirbonyeh N., Akbari A. (2020). Prevalence of underlying diseases in hospitalized patients with COVID-19: a systematic review and meta-analysis. Arch. Acad. Emerg. Med. 8:35.
    1. Felsenstein S., Hedrich C. M. (2020). COVID-19 in children and young people. Lancet Rheumatol. 2 e514–e516.
    1. Ferrari F. (2020). COVID-19: updated data and its relation to the cardiovascular system. Arq. Bras. Cardiol. 114 823–826. 10.36660/abc.20200215
    1. Fischer A. (2020). Resistance of children to Covid-19. How? Mucosal. Immunol. 13 563–565. 10.1038/s41385-020-0303-9
    1. Gebhart J., Posch F., Koder S., Quehenberger P., Perkmann T., Kuessel L., et al. (2019). High risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant. Blood Adv. 3 769–776. 10.1182/bloodadvances.2018026948
    1. Grasselli G., Zangrillo A., Zanella A., Antonelli M., Cabrini L., Castelli A., et al. (2020). Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 323 1574–1581. 10.1001/jama.2020.5394
    1. Guan W. J., Ni Z. Y., Hu Y., Liang W. H., Ou C. Q., He J. X., et al. (2020). Clinical characteristics of coronavirus disease 2019 in China. N. Engl. J. Med. 382 1708–1720. 10.1056/NEJMoa2002032
    1. Guo T., Fan Y., Chen M., Wu X., Zhang L., He T., et al. (2020). Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol. 5 811–818. 10.1001/jamacardio.2020.1017
    1. Gupta N., Zhao Y. Y., Evans C. E. (2019). The stimulation of thrombosis by hypoxia. Thromb. Res. 181 77–83. 10.1016/j.thromres.2019.07.013
    1. Gurwitz D. (2020). Angiotensin receptor blockers as tentative SARS−CoV−2 therapeutics. Drug Dev. Res. 81 537–540. 10.1002/ddr.21656
    1. Guzik T. J., Mohiddin S. A., Dimarco A., Patel V., Savvatis K., Marelli-Berg F. M., et al. (2020). COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc. Res. 116 1666–1687. 10.1093/cvr/cvaa106
    1. Hamming I., Timens W., Bulthuis M. L., Lely A. T., Navis G., van Goor H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 203 631–637. 10.1002/path.1570
    1. Helms J., Tacquard C., Severac F., Leonard-Lorant I., Ohana M., Delabranche X., et al. (2020). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 46 1089–1098. 10.1007/s00134-020-06062-x
    1. Henderson L. A., Canna S. W., Schulert G. S., Volpi S., Lee P. Y., Kernan K. F., et al. (2020). On the alert for cytokine storm: immunopathology in COVID-19. Arthritis Rheumatol. 72 1059–1063. 10.1002/art.41285
    1. Hoffmann M., Kleine-Weber H., Schroeder S., Krüger N., Herrler T., Erichsen S., et al. (2020). SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181 271–280. 10.1016/j.cell.2020.02.052
    1. Hogner K., Wolff T., Pleschka S., Plog S., Gruber A. D., Kalinke U. (2013). Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog. 9:e1003188. 10.1371/journal.ppat.1003188
    1. Hu B., Zeng L. P., Yang X. L., Ge X. Y., Zhang W., Li B., et al. (2017). Discovery of a rich gene pool of bat SARS-related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog. 13:e1006698. 10.1371/journal.ppat.1006698
    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395 497–506. 10.1016/S0140-6736(20)30183-5
    1. Jones V. G., Mills M., Suarez D., Hogan C. A., Yeh D., Bradley Segal J., et al. (2020). COVID-19 and kawasaki disease: novel virus and novel case. Hosp. Pediatr. 10 537–540. 10.1542/hpeds.2020-0123
    1. Kanegaye J. T., Wilder M. S., Molkara D., Frazer J. R., Pancheri J., Tremoulet A. H., et al. (2009). Recognition of a Kawasaki disease shock syndrome. Pediatrics 123, 783–789. 10.1542/peds.2008-1871
    1. Kass D., Duggal P., Cingolani O. (2020). Obesity could shift severe COVID-19 disease to younger ages. Lancet 395 1544–1545. 10.1016/S0140-6736(20)31024-2
    1. Kassir R. (2020). Risk of COVID-19 for patients with obesity. Obes. Rev. 21:e13034. 10.1111/obr.13034
    1. Kassiri Z., Zhong J., Guo D., Basu R., Wang X., Liu P. P., et al. (2009). Loss of angiotensin converting enzyme 2 accelerates maladaptive left ventricular remodeling in response to myocardial infarction. Circ. Heart Fail. 2 446–455. 10.1161/CIRCHEARTFAILURE.108.840124
    1. Katsiki N., Banach M., Mikhailidis D. P. (2020). Lipid-lowering therapy and renin-angiotensin-aldosterone system inhibitors in the era of the COVID-19 pandemic. Arch. Med. Sci. 16 485–489. 10.5114/aoms.2020.94503
    1. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., et al. (2005). A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat. Med. 11 875–879. 10.1038/nm1267
    1. Lee D. W., Gardner R., Porter D. L., Louis C. U., Ahmed N., Jensen M., et al. (2014). Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124 188–195. 10.1182/blood-2014-05-552729
    1. Li B., Yang J., Zhao F., Zhi L., Wang X., Liu L., et al. (2020). Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin. Res. Cardiol. 109 531–538. 10.1007/s00392-020-01626-9
    1. Li Y., Zheng Q., Zou L., Wu J., Guo L., Teng L., et al. (2019). Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition. Pediatr. Rheumatol. Online J. 17:1. 10.1186/s12969-018-0303-4
    1. Libby P., Simon D. I. (2001). Inflammation and thrombosis: the clot thickens. Circulation 103 1718–1720. 10.1161/01.cir.103.13.1718
    1. Liu K., Fang Y. Y., Deng Y., Liu W., Wang M. F., Ma J. P. (2020). Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin. Med. J. (Engl) 133 1025–1031. 10.1097/cm9.0000000000000744
    1. Márquez E. J., Trowbridge J., Kuchel G. A., Banchereau J., Ucar D. (2020). The lethal sex gap: COVID-19. Immun. Ageing 17:13.
    1. Mattioli A. V., Sciomer S., Cocchi C., Maffei S., Gallina S. (2020). Quarantine during COVID-19 outbreak: changes in diet and physical activity increase the risk of cardiovascular disease. Nutr. Metab. Cardiovasc. Dis. 30 1409–1417. 10.1016/j.numecd.2020.05.020
    1. McGonagle D., Sharif K., O’Regan A., Bridgewood C. (2020). The role of cytokines including interleukin-6 in COVID-19 induced Pneumonia and macrophage activation syndrome-like disease. Autoimmun. Rev. 19:102537. 10.1016/j.autrev.2020.102537
    1. Mehta P. K., Griendling K. K. (2007). Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am. J. Physiol. 292 82–97. 10.1152/ajpcell.00287.2006
    1. Murthy H., Iqbal M., Chavez J. C., Kharfan-Dabaja M. A. (2019). Cytokine release syndrome: current perspectives. Immunotargets Ther. 8 43–52. 10.2147/ITT.S202015
    1. Newburger J. W., Takahashi M., Gerber M. A., Gewitz M. H., Tani L. Y., Burns J. C., et al. (2004). Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circulation 110 2747–2771. 10.1161/01.CIR.0000145143.19711.78
    1. Oudit G. Y., Kassiri Z., Jiang C., Liu P. P., Poutanen S. M., Penninger J. M., et al. (2009). SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur. J. Clin. Invest. 39 618–625. 10.1111/j.1365-2362.2009.02153.x
    1. Pagliaro P. (2020). Is macrophages heterogeneity important in determining COVID-19 lethality? Med. Hypotheses 143:110073. 10.1016/j.mehy.2020.110073
    1. Palmieri L., Andrianou X., Barbariol P., Bella A., Bellino S., Benelli E. (2020). Characteristics of SARS-CoV-2 Patients dying in Italy Report based on available data on May 21st, 2020. Available online at: (accessed April 23, 2020).
    1. Park S., Lee H. Y., Cho E. J., Sung K. C., Kim J., Kim D. H., et al. (2020). Is the use of RAS inhibitors safe in the current era of COVID-19 pandemic? Clin Hypertens. 26:11. 10.1186/s40885-020-00144-0
    1. Patel V. B., Bodiga S., Basu R., Das S. K., Wang W., Wang Z., et al. (2012). Loss of angiotensin converting enzyme-2 exacerbates diabetic cardiovascular complications and leads to systolic and vascular dysfunction: a critical role of the angiotensin II/AT1 receptor axis. Circ. Res. 110 1322–1335. 10.1161/CIRCRESAHA.112.268029
    1. Patel V. B., Clarke N., Wang Z., Fan D., Parajuli N., Basu R., et al. (2014). Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS. J. Mol. Cell. Cardiol. 66 167–176. 10.1016/j.yjmcc.2013.11.017
    1. Penna C., Mercurio V., Tocchetti C. G., Pagliaro P. (2020). Sex−related differences in COVID−19 lethality. Br. J. Pharmacol. 177 4375–4385. 10.1111/bph.15207
    1. Phadke M., Saunik S. (2020). Use of angiotensin receptor blockers such as Telmisartan, Losartsan in nCoV Wuhan Corona Virus infections—Novel mode of treatment. BMJ 368:406. 10.1136/bmj.m406
    1. Reiner Ž, Hatamipour M., Banach M., Pirro M., Al-Rasadi K., Jamialahmadi T., et al. (2020). Statins and the COVID-19 main protease: in silico evidence on direct interaction. Arch. Med. Sci. 16 490–496. 10.5114/aoms.2020.94655
    1. Richardson S., Hirsch J. S., Narasimhan M., Crawford D. M., McGinn T., Davidson K. W., et al. (2020). Presenting characteristics, Comorbidities, and outcomes among 5700 patients hospitalized With COVID-19 in the New York City area. JAMA 323 2052–2059. 10.1001/jama.2020.6775
    1. Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P., Hennekens C. H. (1997). Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N. Engl. J. Med. 336 973–979. 10.1056/NEJM199704033361401
    1. Riphagen S., Gomez X., Gonzalez-Martinez C., Wilkinson N., Theocharis P. (2020). Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395 1607–1608. 10.1016/S0140-6736(20)31094-1
    1. Shi S., Qin M., Shen B., Cai Y., Liu T., Yang F., et al. (2020). Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol. 5 802–810. 10.1001/jamacardio.2020.0950
    1. Shimabukuro-Vornhagen A., Gödel P., Subklewe M., Stemmler H. J., Schlößer H. A., Schlaak M., et al. (2018). Cytokine release syndrome. J. Immunother. Cancer 6:56. 10.1186/s40425-018-0343-9
    1. Shirato K., Imada Y., Kawase M., Nakagaki K., Matsuyama S., Taguchi F. (2014). Possible involvement of infection with human coronavirus 229E, but not NL63, in Kawasaki disease. J. Med. Virol. 86 2146–2153. 10.1002/jmv.23950
    1. Steptoe A., Kivimäki M. (2012). Stress and cardiovascular disease. Nat. Rev. Cardiol. 9 360–370.
    1. Tang N., Li D., Wang X., Sun Z. (2020). Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 18 844–847. 10.1111/jth.14768
    1. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (2020). Vital surveillances: the epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) — China, 2020. China CDC Wkly. 2 113–122. 10.46234/ccdcw2020.032
    1. Vaduganathan M., Vardeny O., Michel T., McMurray J. J. V., Pfeffer M. A., Solomon S. D. (2020). Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N. Engl. J. Med. 382 1653–1659. 10.1056/NEJMsr2005760
    1. Verdecchia P., Cavallini C., Spanevello A., Angeli F. (2020). The pivotal link between ACE2 deficiency and SARS-CoV-2 infection. Eur. J. Intern. Med. 76 14–20. 10.1016/j.ejim.2020.04.037
    1. Verdoni L., Mazza A., Gervasoni A., Martelli L., Ruggeri M., Ciuffreda M., et al. (2020). An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 395 1771–1778. 10.1016/S0140-6736(20)31103-X
    1. Walls A. C., Park Y. J., Tortorici M. A., Wall A., McGuire A. T., Veesler D. (2020). Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181 281–292. 10.1016/j.cell.2020.02.058
    1. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., et al. (2020). Clinical characteristics of 138 hospitalized patients With 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 323 1061–1069. 10.1001/jama.2020.1585
    1. Wang L. (2020). C-reactive protein levels in the early stage of COVID-19. Med. Mal. Infect. 50 332–334. 10.1016/j.medmal.2020.03.007
    1. Wang Z., Zhou Q., Wang C., Shi Q., Lu S., Ma Y., et al. (2020). Clinical characteristics of children with COVID-19: a rapid review and meta-analysis. Ann. Transl. Med. 8:620. 10.21037/atm-20-3302
    1. Whittaker E., Bamford A., Kenny J., Kaforou M., Jones C. E., Shah P., et al. (2020). Clinical Characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated With SARS-CoV-2. JAMA 324 259–269. 10.1001/jama.2020.10369
    1. World Health Organization (2018). WHO Global Action Plan on Physical Activity 2018–2030: More Active People for a Healthier World. Geneva: World Health Organization.
    1. World Health Organization (2020). Multisystem Inflammatory Syndrome in Children and Adolescents with COVID-19. Available online at: (accessed June 23, 2020).
    1. Wu D., Yang X. O. (2020). TH17 responses in cytokine storm of COVID-19: an emerging target of JAK2 inhibitor Fedratinib. J. Microbiol. Immunol. Infect. 53 368–370. 10.1016/j.jmii.2020.03.005
    1. Wu Z., McGoogan J. M. (2020). Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA 323 1239–1242. 10.1001/jama.2020.2648
    1. Xiong T. Y., Redwood S., Prendergast B., Chen M. (2020). Coronaviruses and the cardiovascular system: acute and long-term implications. Eur. Heart J. 41 1798–1800. 10.1093/eurheartj/ehaa231
    1. Xu X., Han M., Li T., Sun W., Wang D., Fu B., et al. (2020). Effective treatment of severe COVID-19 patients with tocilizumab. Proc. Natl. Acad. Sci. U.S.A. 117 10970–10975. 10.1073/pnas.2005615117
    1. Yan S. F., Mackman N., Kisiel W., Stern D. M., Pinsky D. J. (1999). Hypoxia/Hypoxemia-Induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis. Arterioscler. Thromb. Vasc. Biol. 19 2029–2035. 10.1161/01.atv.19.9.2029
    1. Ye Q., Wang B., Mao J. (2020). The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. J. Infect. 80 607–613. 10.1016/j.jinf.2020.03.037
    1. Yu B., Steptoe A., Chen L. J., Chen Y. H., Lin C. H., Ku P. W. (2020). Social isolation, loneliness, and all-cause mortality in patients with cardiovascular disease: a 10-year follow-up study. Psychosom. Med. 82 208–214. 10.1097/psy.0000000000000777
    1. Zhang H., Penninger J. M., Li Y., Zhong N., Slutsky A. S. (2020). Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 46 586–590. 10.1007/s00134-020-05985-9
    1. Zhang J., Yang Y., Yang N., Ma Y., Zhou Q., Li W., et al. (2020). Effectiveness of intravenous immunoglobulin for children with severe COVID-19: a rapid review. Ann. Transl. Med. 8:625. 10.21037/atm-20-3305
    1. Zhao M., Wang M., Zhang J., Ye J., Xu Y., Wang Z., et al. (2020). Advances in the relationship between coronavirus infection and cardiovascular diseases. Biomed. Pharmacother. 127:110230. 10.1016/j.biopha.2020.110230
    1. Zheng S., Fan J., Yu F., Feng B., Lou B., Zou Q., et al. (2020). Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ 369:m1443. 10.1136/bmj.m1443
    1. Zheng Y. Y., Ma Y. T., Zhang J. Y., Xie X. (2020). COVID-19 and the cardiovascular system. Nat. Rev. Cardiol. 17 259–260.
    1. Zhong J., Basu R., Guo D., Chow F. L., Byrns S., Schuster M., et al. (2010). Angiotensin-converting enzyme 2 suppresses pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction. Circulation 122 717–728. 10.1161/CIRCULATIONAHA.110.955369
    1. Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., et al. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395 1054–1062. 10.1016/S0140-6736(20)30566-3
    1. Zhou P., Yang X. L., Wang X. G., Hu B., Zhang L., Zhang W., et al. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579 270–273. 10.1038/s41586-020-2012-7

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