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Review article: Biomedical intelligence

Vol. 150 No. 5153 (2020)

Cardiovascular aspects of COVID-19

  • David J. Kurz
  • Franz R. Eberli
DOI
https://doi.org/10.4414/smw.2020.20417
Cite this as:
Swiss Med Wkly. 2020;150:w20417
Published
31.12.2020

Summary

Coronavirus disease 2019 (COVID-19) is primarily a pulmonary disease, but also affects the cardiovascular system in multiple ways. In this review, we will summarise and put into perspective findings and debates relating to the diverse aspects of cardiovascular involvement of COVID-19. We will review evidence for the role of the renin-angiotensin-aldosterone system (RAAS), the risk of pre-existing cardiovascular disease in COVID-19 susceptibility and course, and the mechanism of acute and long-term myocardial injury.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses membrane-bound angiotensin converting-enzyme-2 (ACE2) as a receptor for cell entry. ACE2 is part of an important counter-regulatory circuit antagonising the harmful effects of angiotensin II on lung and heart. Modulation of ACE2 may therefore affect disease susceptibility and disease course. However, observational clinical studies and one randomised trial have so far not yielded evidence for harmful or beneficial effects of blockers of the RAAS during COVID-19. Age, gender, and multi-morbidity all increase susceptibility to SARS-CoV-2. In contrast, pre-existing cardiovascular diseases do so only minimally, but they may aggravate the disease course.

Direct SARS-CoV-2 infection of the heart tissue and myocytes is rare. Nevertheless, COVID-19 may lead to myocarditis-like acute cardiac injury, characterised by myocardial oedema, but lacking extensive myocyte loss and lymphocytic infiltration. Independent of this, increases in cardiac biomarkers (troponin, N-terminal pro-brain natriuretic peptide, D-dimer) are frequent, especially in the phase of severe systemic inflammation and acute respiratory distress syndrome, and quantitatively associated with poor outcome. The pulmonary infection may result initially in right ventricular dysfunction, but in cases with severe systemic infection hypoxia, hyperinflammation and cytokine storm heart failure may eventually ensue.

Unlike other infections and inflammatory states, COVID-19 does not appear to trigger acute coronary syndromes. In children, even mild COVID-19 can induce a multisystem inflammatory syndrome with Kawasaki-like symptoms frequently accompanied by cardiogenic shock.

References

  1. https://www.bag.admin.ch/bag/de/home/krankheiten/ausbrueche-epidemien-pandemien/aktuelle-ausbrueche-epidemien/novel-cov/situation-schweiz-und-international.html.
  2. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med. 2020;26(4):450–2. doi:.https://doi.org/10.1038/s41591-020-0820-9
  3. Zhang T, Wu Q, Zhang Z. Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak. Curr Biol. 2020;30(7):1346–1351.e2. doi:.https://doi.org/10.1016/j.cub.2020.03.022
  4. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271–280.e8. doi:.https://doi.org/10.1016/j.cell.2020.02.052
  5. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7. doi:.https://doi.org/10.1002/path.1570
  6. Gheblawi M, Wang K, Viveiros A, Nguyen Q, Zhong JC, Turner AJ, 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):1456–74. doi:.https://doi.org/10.1161/CIRCRESAHA.120.317015
  7. McIntosh K, Hirsch M, Bloom A. Coronavirus Disease 19 (COVID-19). UpToDate. 2020.
  8. Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020;5(7):745–7. doi:.https://doi.org/10.1001/jamacardio.2020.1282
  9. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):811–8. doi:.https://doi.org/10.1001/jamacardio.2020.1017
  10. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al.; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708–20. doi:.https://doi.org/10.1056/NEJMoa2002032
  11. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;324(8):782–93. doi:.https://doi.org/10.1001/jama.2020.12839
  12. Lechien JR, Chiesa-Estomba CM, De Siati DR, Horoi M, Le Bon SD, Rodriguez A, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;277(8):2251–61. doi:.https://doi.org/10.1007/s00405-020-05965-1
  13. Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020;7(6):e438–40. doi:.https://doi.org/10.1016/S2352-3026(20)30145-9
  14. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405–7. doi:.https://doi.org/10.1016/j.healun.2020.03.012
  15. Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91–5. doi:.https://doi.org/10.1016/j.ijid.2020.03.017
  16. Wu Z, McGoogan JM. 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. 2020;323(13):1239–42. doi:.https://doi.org/10.1001/jama.2020.2648
  17. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17(5):259–60. doi:.https://doi.org/10.1038/s41569-020-0360-5
  18. Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. J Travel Med. 2020;27(3):taaa041. doi:.https://doi.org/10.1093/jtm/taaa041
  19. Watkins J. Preventing a covid-19 pandemic. BMJ. 2020;368:m810. doi:.https://doi.org/10.1136/bmj.m810
  20. Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med. 2020;382(17):1653–9. doi:.https://doi.org/10.1056/NEJMsr2005760
  21. Kuster GM, Pfister O, Burkard T, Zhou Q, Twerenbold R, Haaf P, et al. SARS-CoV2: should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19? Eur Heart J. 2020;41(19):1801–3. doi:.https://doi.org/10.1093/eurheartj/ehaa235
  22. Wang K, Gheblawi M, Oudit GY. Angiotensin Converting Enzyme 2: A Double-Edged Sword. Circulation. 2020;142(5):426–8. doi:.https://doi.org/10.1161/CIRCULATIONAHA.120.047049
  23. Zhang J, Wang M, Ding W, Wan J. The interaction of RAAS inhibitors with COVID-19: Current progress, perspective and future. Life Sci. 2020;257:118142. doi:.https://doi.org/10.1016/j.lfs.2020.118142
  24. Oudit GY, Pfeffer MA. Plasma angiotensin-converting enzyme 2: novel biomarker in heart failure with implications for COVID-19. Eur Heart J. 2020;41(19):1818–20. doi:.https://doi.org/10.1093/eurheartj/ehaa414
  25. Sama IE, Ravera A, Santema BT, van Goor H, Ter Maaten JM, Cleland JGF, et al. Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors. Eur Heart J. 2020;41(19):1810–7. doi:.https://doi.org/10.1093/eurheartj/ehaa373
  26. Milne S, Yang CX, Timens W, Bossé Y, Sin DD. SARS-CoV-2 receptor ACE2 gene expression and RAAS inhibitors. Lancet Respir Med. 2020;8(6):e50–1. doi:.https://doi.org/10.1016/S2213-2600(20)30224-1
  27. Dauchet L, Lambert M, Gauthier JP, Poissy J, Faure K, Facon A, et al. ACE inhibitors, ATI receptor blockers and COVID-19: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study. medRxiv. 2020.
  28. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19. N Engl J Med. 2020;382(25):2431–40. doi:.https://doi.org/10.1056/NEJMoa2006923
  29. Mehta N, Kalra A, Nowacki AS, Anjewierden S, Han Z, Bhat P, et al. Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(9):1020–6. doi:.https://doi.org/10.1001/jamacardio.2020.1855
  30. Reynolds HR, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, et al. Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19. N Engl J Med. 2020;382(25):2441–8. doi:.https://doi.org/10.1056/NEJMoa2008975
  31. Huang Z, Cao J, Yao Y, Jin X, Luo Z, Xue Y, et al. The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension. Ann Transl Med. 2020;8(7):430. doi:.https://doi.org/10.21037/atm.2020.03.229
  32. Li J, Wang X, Chen J, Zhang H, Deng A. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020;5(7):825–30. doi:.https://doi.org/10.1001/jamacardio.2020.1624
  33. Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie 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):1671–81. doi:.https://doi.org/10.1161/CIRCRESAHA.120.317134
  34. Lopes RD, Macedo AVS, de Barros E Silva PGM, Moll-Bernardes RJ, Feldman A, D’Andréa Saba Arruda G, et al.; BRACE CORONA investigators. Continuing versus suspending angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: Impact on adverse outcomes in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)--The BRACE CORONA Trial. Am Heart J. 2020;226:49–59. doi:.https://doi.org/10.1016/j.ahj.2020.05.002
  35. Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, et al. The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1-7). Physiol Rev. 2018;98(1):505–53. doi:.https://doi.org/10.1152/physrev.00023.2016
  36. Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015;116(6):960–75. doi:.https://doi.org/10.1161/CIRCRESAHA.116.303587
  37. Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875–9. doi:.https://doi.org/10.1038/nm1267
  38. Zou Z, Yan Y, Shu Y, Gao R, Sun Y, Li X, et al. Angiotensin-converting enzyme 2 protects from lethal avian influenza A H5N1 infections. Nat Commun. 2014;5(1):3594. doi:.https://doi.org/10.1038/ncomms4594
  39. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and Cardiovascular Disease. Circulation. 2020;141(20):1648–55. doi:.https://doi.org/10.1161/CIRCULATIONAHA.120.046941
  40. Chen T, Wu D, Chen H, Yan W, Yang D, Chen G, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020;368:m1091. doi:.https://doi.org/10.1136/bmj.m1091
  41. Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934–43. doi:.https://doi.org/10.1001/jamainternmed.2020.0994
  42. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, 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):1054–62. doi:.https://doi.org/10.1016/S0140-6736(20)30566-3
  43. Hu S, Gao R, Liu L, et al. Summary of the 2018 report on cardiovascular disease in China. Chin Circ J. 2019;34:209.
  44. Liu M, Liu SW, Wang LJ, Bai YM, Zeng XY, Guo HB, et al. Burden of diabetes, hyperglycaemia in China from to 2016: Findings from the 1990 to 2016, global burden of disease study. Diabetes Metab. 2019;45(3):286–93. doi:.https://doi.org/10.1016/j.diabet.2018.08.008
  45. Meyer P, Degrauwe S, Van Delden C, Ghadri JR, Templin C. Typical takotsubo syndrome triggered by SARS-CoV-2 infection. Eur Heart J. 2020;41(19):1860. doi:.https://doi.org/10.1093/eurheartj/ehaa306
  46. Sala S, Peretto G, Gramegna M, Palmisano A, Villatore A, Vignale D, et al. Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection. Eur Heart J. 2020;41(19):1861–2. doi:.https://doi.org/10.1093/eurheartj/ehaa286
  47. Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res. 2020;116(6):1097–100. doi:.https://doi.org/10.1093/cvr/cvaa078
  48. Nicin L, Abplanalp WT, Mellentin H, Kattih B, Tombor L, John D, et al. Cell type-specific expression of the putative SARS-CoV-2 receptor ACE2 in human hearts. Eur Heart J. 2020;41(19):1804–6. doi:.https://doi.org/10.1093/eurheartj/ehaa311
  49. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417–8. doi:.https://doi.org/10.1016/S0140-6736(20)30937-5
  50. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846–8. doi:.https://doi.org/10.1007/s00134-020-05991-x
  51. Esposito A, Palmisano A, Natale L, Ligabue G, Peretto G, Lovato L, et al. Cardiac Magnetic Resonance Characterization of Myocarditis-Like Acute Cardiac Syndrome in COVID-19. JACC Cardiovasc Imaging. 2020;13(11):2462–5. doi:.https://doi.org/10.1016/j.jcmg.2020.06.003
  52. Dolhnikoff M, Ferreira Ferranti J, de Almeida Monteiro RA, Duarte-Neto AN, Soares Gomes-Gouvêa M, Viu Degaspare N, et al. SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome. Lancet Child Adolesc Health. 2020;4(10):790–4. doi:.https://doi.org/10.1016/S2352-4642(20)30257-1
  53. Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin. Eur Heart J. 2020;ehaa190. doi:.https://doi.org/10.1093/eurheartj/ehaa190
  54. Inciardi RM, Lupi L, Zaccone G, Italia L, Raffo M, Tomasoni D, et al. Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(7):819–24. doi:.https://doi.org/10.1001/jamacardio.2020.1096
  55. Kim IC, Kim JY, Kim HA, Han S. COVID-19-related myocarditis in a 21-year-old female patient. Eur Heart J. 2020;41(19):1859. doi:.https://doi.org/10.1093/eurheartj/ehaa288
  56. Doyen D, Moceri P, Ducreux D, Dellamonica J. Myocarditis in a patient with COVID-19: a cause of raised troponin and ECG changes. Lancet. 2020;395(10235):1516. doi:.https://doi.org/10.1016/S0140-6736(20)30912-0
  57. Tavazzi G, Pellegrini C, Maurelli M, Belliato M, Sciutti F, Bottazzi A, et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail. 2020;22(5):911–5. doi:.https://doi.org/10.1002/ejhf.1828
  58. Lindner D, Fitzek A, Bräuninger H, Aleshcheva G, Edler C, Meissner K, et al. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol. 2020;5(11):1281–5. doi:.https://doi.org/10.1001/jamacardio.2020.3551
  59. Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med. 2020;173(4):268–77. doi:.https://doi.org/10.7326/M20-2003
  60. Oudit GY, Kassiri Z, Jiang C, Liu PP, Poutanen SM, Penninger JM, et al. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest. 2009;39(7):618–25. doi:.https://doi.org/10.1111/j.1365-2362.2009.02153.x
  61. Wenzel P, Kopp S, Göbel S, Jansen T, Geyer M, Hahn F, et 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):1661–3. doi:.https://doi.org/10.1093/cvr/cvaa160
  62. Basso C, Leone O, Rizzo S, De Gaspari M, van der Wal AC, Aubry MC, et al. Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study. Eur Heart J. 2020;41(39):3827–35. doi:.https://doi.org/10.1093/eurheartj/ehaa664
  63. Halushka MK, Vander Heide RS. Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations. Cardiovasc Pathol. 2020;50:107300. doi:.https://doi.org/10.1016/j.carpath.2020.107300
  64. Puntmann VO, Carerj ML, Wieters I, Fahim M, Arendt C, Hoffmann J, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(11):1265–73. doi:.https://doi.org/10.1001/jamacardio.2020.3557
  65. Eiros R, Barreriro-Perez M, Martin-Garcia A, Almeida J, Villacorta E, Perez-Pons A, et al. Pericarditis and myocarditis long after SARS-CoV-2 infection: a cross-sectional descriptive study in health-care workers. medRxiv. doi:.https://doi.org/10.1101/2020.07.12.20151316
  66. 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.120.047549
  67. Gao C, Wang Y, Gu X, Shen X, Zhou D, Zhou S, et al.; Community-Acquired Pneumonia–China Network. Association Between Cardiac Injury and Mortality in Hospitalized Patients Infected With Avian Influenza A (H7N9) Virus. Crit Care Med. 2020;48(4):451–8. doi:.https://doi.org/10.1097/CCM.0000000000004207
  68. Valaperti A, Nishii M, Liu Y, Naito K, Chan M, Zhang L, et al. Innate immune interleukin-1 receptor-associated kinase 4 exacerbates viral myocarditis by reducing CCR5(+) CD11b(+) monocyte migration and impairing interferon production. Circulation. 2013;128(14):1542–54. doi:.https://doi.org/10.1161/CIRCULATIONAHA.113.002275
  69. Flores D, Walter J, Wussler D, et al. Direct comparison of high-sensitivity cardiac troponin T and I for prediction of mortality in patients with pneumonia. J Clin Chem Lab Med. 2019;2:2.
  70. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020;382(21):2012–22. doi:.https://doi.org/10.1056/NEJMoa2004500
  71. Szekely Y, Lichter Y, Taieb P, Banai A, Hochstadt A, Merdler I, et al. Spectrum of Cardiac Manifestations in COVID-19: A Systematic Echocardiographic Study. Circulation. 2020;142(4):342–53. doi:.https://doi.org/10.1161/CIRCULATIONAHA.120.047971
  72. Khoury J, Arow M, Elias A, Makhoul BF, Berger G, Kaplan M, et al. The prognostic value of brain natriuretic peptide (BNP) in non-cardiac patients with sepsis, ultra-long follow-up. J Crit Care. 2017;42:117–22. doi:.https://doi.org/10.1016/j.jcrc.2017.07.009
  73. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, 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
  74. Tang 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;18(4):844–7. doi:.https://doi.org/10.1111/jth.14768
  75. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120–8. doi:.https://doi.org/10.1056/NEJMoa2015432
  76. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res. 2020;220:1–13. doi:.https://doi.org/10.1016/j.trsl.2020.04.007
  77. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16–32. doi:.https://doi.org/10.1128/MMBR.05015-11
  78. Chau VQ, Oliveros E, Mahmood K, Singhvi A, Lala A, Moss N, et al. The Imperfect Cytokine Storm: Severe COVID-19 With ARDS in a Patient on Durable LVAD Support. JACC Case Rep. 2020;2(9):1315–20. doi:.https://doi.org/10.1016/j.jaccas.2020.04.001
  79. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033–4. doi:.https://doi.org/10.1016/S0140-6736(20)30628-0
  80. Kang S, Tanaka T, Inoue H, Ono C, Hashimoto S, Kioi Y, et al. IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome. Proc Natl Acad Sci USA. 2020;117(36):22351–6. doi:.https://doi.org/10.1073/pnas.2010229117
  81. Kox M, Waalders NJB, Kooistra EJ, Gerretsen J, Pickkers P. Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions. JAMA. 2020;324(15):1565–7. doi:.https://doi.org/10.1001/jama.2020.17052
  82. Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. Front Immunol. 2020;11:1708. doi:.https://doi.org/10.3389/fimmu.2020.01708
  83. Mafham MM, Spata E, Goldacre R, Gair D, Curnow P, Bray M, et al. COVID-19 pandemic and admission rates for and management of acute coronary syndromes in England. Lancet. 2020;396(10248):381–9. doi:.https://doi.org/10.1016/S0140-6736(20)31356-8
  84. Gluckman TJ, Wilson MA, Chiu ST, Penny BW, Chepuri VB, Waggoner JW, et al. Case Rates, Treatment Approaches, and Outcomes in Acute Myocardial Infarction During the Coronavirus Disease 2019 Pandemic. JAMA Cardiol. 2020. doi:.https://doi.org/10.1001/jamacardio.2020.3629
  85. Tam CF, Cheung KS, Lam S, Wong A, Yung A, Sze M, et al. Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on ST-Segment-Elevation Myocardial Infarction Care in Hong Kong, China. Circ Cardiovasc Qual Outcomes. 2020;13(4):e006631. doi:.https://doi.org/10.1161/CIRCOUTCOMES.120.006631
  86. Belhadjer Z, Méot M, Bajolle F, Khraiche D, Legendre A, Abakka S, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation. 2020;142(5):429–36. doi:.https://doi.org/10.1161/CIRCULATIONAHA.120.048360
  87. European Centre for Disease Prevention and Control. Rapid risk assessment: paediatric inflammatory multisystem syndrome and SARS-CoV-2 infection in children. 2020 May 15. Available from : https://www.ecdc.europa.eu/en/publications-data/paediatric-inflammatory-multisystem-syndrome-and-sars-cov-2-rapid-risk-assessment.
  88. Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al.; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. 2020;383(4):347–58. doi:.https://doi.org/10.1056/NEJMoa2021756
  89. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al.; Overcoming COVID-19 Investigators; CDC COVID-19 Response Team. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. 2020;383(4):334–46. doi:.https://doi.org/10.1056/NEJMoa2021680
  90. Royal College of Paediatrics and Child Health. Guidance: paediatric multisystem inflammatory syndrome temporally associated with COVID-19. 2020. Available from : https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf.
  91. Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020;10(6):537–40. doi:.https://doi.org/10.1542/hpeds.2020-0123
  92. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395(10237):1607–8. doi:.https://doi.org/10.1016/S0140-6736(20)31094-1
  93. Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771–8. doi:.https://doi.org/10.1016/S0140-6736(20)31103-X
  94. McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation. 2017;135(17):e927–99. doi:.https://doi.org/10.1161/CIR.0000000000000484

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