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Aktuelle Kardiologie 2021; 10(01): 32-38
DOI: 10.1055/a-1319-0964
DOI: 10.1055/a-1319-0964
Kurzübersicht
Endothel, vaskuläre Funktion und COVID-19
Endothelium, Vascular Function and COVID-19
Zusammenfassung
Seit Beginn der COVID-19-Pandemie konnten zahlreiche Erkenntnisse über den 3-phasigen Verlauf einer SARS-CoV-2-Infektion, den Infektionsweg und die Bedeutung einer vaskulären Dysfunktion gewonnen werden. Im Rahmen der Infektion kann es zu einer hyperinflammatorischen Phase mit sekundären Organschäden bis hin zum Tod kommen. Diese schweren Krankheitsverläufe gehen mit einer unkontrollierten Freisetzung von Entzündungsmediatoren und Zytokinen einher. Auf zellulärer Ebene bedingt der membrangebundene ACE-2-Rezeptor die Invasion des Virus und stimuliert über einen 2. Mechanismus die Metalloprotease ADAM17 sowie die Freisetzung von Zytokinen. Vasokonstriktive Veränderungen sowie die systemischen Inflammationsreaktionen führen zu hypoxischen Organschäden und thrombotischen Komplikationen. Die mikrovaskuläre Dysfunktion, Mikroangiopathien – insbesondere der kleinen Lungengefäße – sowie eine Endotheliitis können Erklärungsansätze für die ausgeprägte systemische, mikrovaskuläre Störung bei schweren Infektionen mit SARS-CoV-2 liefern.
Abstract
The global involvement of coronavirus disease 19 (COVID-19) provokes multiple findings about the clinical course in three phases, the infection pathway and the vascular function. Severe course of SARS-CoV-2-infection is defined as massive inflammatory reaction with elevated pro-inflammatory cytokines resulting in acute respiratory stress syndrome and the involvement of secondary organ damages with even life-threatening cardiovascular and pulmonary complications. Mechanistically, SARS-CoV-2 invades human cells with binding at angiotensin converting enzyme 2 and following another secondary pathway with ADAM17-mediated systemic release of cytokines and pro-inflammatory markers. Systemic inflammation and vasoconstriction lead to hypoxia and pro-thrombotic complications. Microvascular dysfunction, microangiopathy of small lung vessels and endotheliitis may provide new approaches for systemic inflammation due to SARS-CoV-2 infection.
Was ist wichtig?
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In der hyperinflammatorischen Phase der COVID-19-Erkrankung kommt es zu einer massiven Zytokinfreisetzung und zu sekundären Organschäden.
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Am Zelleintritt von SARS-CoV-2 sind der humane ACE-2-Rezeptor und die transmembrane Serinprotease TMPRSS2 beteiligt, und über die Aktivierung der Metalloproteinase ADAM17 kann – Tumornekrosefaktor-α-vermittelt – ein systemischer Zytokinsturm angestoßen werden.
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Ein systemischer prothrombotischer Status, Mikroangiopathien und eine Endotheliitis selbst sind Erklärungsansätze für die schwere mikrovaskuläre Störung bei schweren Verläufen einer COVID-19-Erkrankung.
Publication History
Article published online:
17 December 2020
© 2020. Thieme. All rights reserved.
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Literatur
- 1 Wu Z, McGoogan JM. 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; 323: 1239-1242 doi:10.1001/jama.2020.2648
- 2 Thygesen K, Alpert JS, Jaffe AS. et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019; 40: 237-269 doi:10.1093/eurheartj/ehy462
- 3 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: 1054-1062 doi:10.1016/S0140-6736(20)30566-3
- 4 Akhmerov A, Marban E. COVID-19 and the Heart. Circ Res 2020; 126: 1443-1455 doi:10.1161/CIRCRESAHA.120.317055
- 5 Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant 2020; 39: 405-407 doi:10.1016/j.healun.2020.03.012
- 6 Peiris JS, Chu CM, Cheng VC. et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003; 361: 1767-1772 doi:10.1016/s0140-6736(03)13412-5
- 7 Guzik TJ, Mohiddin SA, Dimarco A. et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res 2020; 116: 1666-1687 doi:10.1093/cvr/cvaa106
- 8 Guo T, Fan Y, Chen M. et al. Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19). JAMA Cardiol 2020; 5: 811-818 doi:10.1001/jamacardio.2020.1017
- 9 Tavazzi G, Pellegrini C, Maurelli M. et al. Myocardial localization of coronavirus in COVID-19 cardiogenic shock. Eur J Heart Fail 2020; 22: 911-915 doi:10.1002/ejhf.1828
- 10 Zeng JH, Liu YX, Yuan J. et al. First case of COVID-19 complicated with fulminant myocarditis: a case report and insights. Infection 2020; 48: 773-777 doi:10.1007/s15010-020-01424-5
- 11 Wenzel P, Kopp S, Gobel S. 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: 1661-1663 doi:10.1093/cvr/cvaa160
- 12 Escher F, Pietsch H, Aleshcheva G. et al. Detection of viral SARS-CoV-2 genomes and histopathological changes in endomyocardial biopsies. ESC Heart Fail 2020; 7: 2440-2447 doi:10.1002/ehf2.12805
- 13 Lindner D, Fitzek A, Brauninger H. et al. Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases. JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.3551.
- 14 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: 1061-1069 doi:10.1001/jama.2020.1585
- 15 Ruan 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; 46: 846-848 doi:10.1007/s00134-020-05991-x
- 16 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506 doi:10.1016/S0140-6736(20)30183-5
- 17 Mehta P, McAuley DF, Brown M. et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033-1034 doi:10.1016/S0140-6736(20)30628-0
- 18 Wu C, Chen X, Cai Y. 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: 934-943 doi:10.1001/jamainternmed.2020.0994
- 19 Akbari H, Tabrizi R, Lankarani KB. et al. The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Life Sci 2020; 258: 118167 doi:10.1016/j.lfs.2020.118167
- 20 Qin C, Zhou L, Hu Z. et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020; 71: 762-768 doi:10.1093/cid/ciaa248
- 21 Chen X, Huang J, Huang Y. et al. Characteristics of immune cells and cytokines in patients with coronavirus disease 2019 in Guangzhou, China. Hum Immunol 2020; 81: 702-708 doi:10.1016/j.humimm.2020.08.006
- 22 Schulte-Schrepping J, Reusch N, Paclik D. et al. Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell 2020; 182: 1419-1440.e23 doi:10.1016/j.cell.2020.08.001
- 23 Silvin A, Chapuis N, Dunsmore G. et al. Elevated Calprotectin and Abnormal Myeloid Cell Subsets Discriminate Severe from Mild COVID-19. Cell 2020; 182: 1401-1418.e18 doi:10.1016/j.cell.2020.08.002
- 24 Patel VB, Zhong JC, Grant MB. et al. Role of the ACE2/Angiotensin 1–7 Axis of the Renin-Angiotensin System in Heart Failure. Circ Res 2016; 118: 1313-1326 doi:10.1161/CIRCRESAHA.116.307708
- 25 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; 14: 185-192 doi:10.1007/s11684-020-0754-0
- 26 Gheblawi M, Wang K, Viveiros A. 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: 1456-1474 doi:10.1161/CIRCRESAHA.120.317015
- 27 Walls AC, Park YJ, Tortorici MA. et al. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020; 181: 281-292.e6 doi:10.1016/j.cell.2020.02.058
- 28 Li W, Moore MJ, Vasilieva N. et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426: 450-454 doi:10.1038/nature02145
- 29 Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5: 562-569 doi:10.1038/s41564-020-0688-y
- 30 Liu L, Wang P, Nair MS. et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature 2020; 584: 450-456 doi:10.1038/s41586-020-2571-7
- 31 Shang J, Ye G, Shi K. et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020; 581: 221-224 doi:10.1038/s41586-020-2179-y
- 32 Millet JK, Whittaker GR. Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res 2015; 202: 120-134 doi:10.1016/j.virusres.2014.11.021
- 33 Hoffmann M, Kleine-Weber H, Schroeder 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: 271-280.e8 doi:10.1016/j.cell.2020.02.052
- 34 Sungnak W, Huang N, Becavin C. et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med 2020; 26: 681-687 doi:10.1038/s41591-020-0868-6
- 35 Wang K, Gheblawi M, Oudit GY. Angiotensin Converting Enzyme 2: A Double-Edged Sword. Circulation 2020; 126: 1456-1474 doi:10.1161/CIRCULATIONAHA.120.047049
- 36 Liu 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; 63: 364-374 doi:10.1007/s11427-020-1643-8
- 37 Clerkin KJ, Fried JA, Raikhelkar J. et al. COVID-19 and Cardiovascular Disease. Circulation 2020; 141: 1648-1655 doi:10.1161/CIRCULATIONAHA.120.046941
- 38 Chen L, Li X, Chen M. et al. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2. Cardiovasc Res 2020; 116: 1097-1100 doi:10.1093/cvr/cvaa078
- 39 Fox SE, Akmatbekov A, Harbert JL. et al. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med 2020; 8: 681-686 doi:10.1016/S2213-2600(20)30243-5
- 40 Del Turco S, Vianello A, Ragusa R. et al. COVID-19 and cardiovascular consequences: Is the endothelial dysfunction the hardest challenge?. Thromb Res 2020; 196: 143-151 doi:10.1016/j.thromres.2020.08.039
- 41 Gavriilaki E, Anyfanti P, Gavriilaki M. et al. Endothelial Dysfunction in COVID-19: Lessons Learned from Coronaviruses. Curr Hypertens Rep 2020; 22: 63 doi:10.1007/s11906-020-01078-6
- 42 Nicolai L, Leunig A, Brambs S. et al. Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated With Respiratory Failure and Coagulopathy. Circulation 2020; 142: 1176-1189 doi:10.1161/CIRCULATIONAHA.120.048488
- 43 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395: 1417-1418 doi:10.1016/S0140-6736(20)30937-5
- 44 Libby P, Luscher T. COVID-19 is, in the end, an endothelial disease. Eur Heart J 2020; 41: 3038-3044 doi:10.1093/eurheartj/ehaa623
- 45 Chen X, Zhao B, Qu Y. et al. Detectable serum SARS-CoV-2 viral load (RNAaemia) is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients. Clin Infect Dis 2020; 71: 1937-1942 doi:10.1093/cid/ciaa449
- 46 Flammer AJ, Anderson T, Celermajer DS. et al. The assessment of endothelial function: from research into clinical practice. Circulation 2012; 126: 753-767 doi:10.1161/CIRCULATIONAHA.112.093245
- 47 Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Thromb Vasc Biol 2003; 23: 168-175 doi:10.1161/01.atv.0000051384.43104.fc
- 48 Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol 2003; 284: R1-R12 doi:10.1152/ajpregu.00323.2002
- 49 Schulz E, Jansen T, Wenzel P. et al. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal 2008; 10: 1115-1126 doi:10.1089/ars.2007.1989
- 50 Incalza MA, DʼOria R, Natalicchio A. et al. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol 2018; 100: 1-19 doi:10.1016/j.vph.2017.05.005
- 51 Kwong JC, Schwartz KL, Campitelli MA. et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med 2018; 378: 345-353 doi:10.1056/NEJMoa1702090
- 52 Dhakal BP, Sweitzer NK, Indik JH. et al. SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart. Heart Lung Circ 2020; 29: 973-987 doi:10.1016/j.hlc.2020.05.101
- 53 Nicholls JM, Poon LL, Lee KC. et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet 2003; 361: 1773-1778 doi:10.1016/s0140-6736(03)13413-7
- 54 Ackermann M, Verleden SE, Kuehnel M. et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med 2020; 383: 120-128 doi:10.1056/NEJMoa2015432
- 55 Elsoukkary SS, Mostyka M, Dillard A. et al. Autopsy Findings in 32 Patients with COVID-19: A Single-Institution Experience. Pathobiology 2020; DOI: 10.1159/000511325.
- 56 Menter T, Haslbauer JD, Nienhold R. et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 2020; 77: 198-209 doi:10.1111/his.14134
- 57 Goldsmith CS, Miller SE, Martines RB. et al. Electron microscopy of SARS-CoV-2: a challenging task. Lancet 2020; 395: e99 doi:10.1016/S0140-6736(20)31188-0
- 58 Verdoni L, Mazza A, Gervasoni A. 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: 1771-1778 doi:10.1016/S0140-6736(20)31103-X
- 59 Evans PC, Ed Rainger G, Mason JC. et al. Endothelial dysfunction in COVID-19: a position paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science. Cardiovasc Res 2020; 116: 2177-2184 doi:10.1093/cvr/cvaa230
- 60 Celermajer DS, Sorensen KE, Gooch VM. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111-1115 doi:10.1016/0140-6736(92)93147-f
- 61 Yoganandamoorthy S, Munasinghe MADSN, Wanigasuriya LVU. et al. Non-invasive assessment of endothelial dysfunction: A novel method to predict severe COVID-19?. Med Hypotheses 2020; 144: 110229 doi:10.1016/j.mehy.2020.110229
- 62 Emanueli C, Badimon L, Martelli F. et al. Call to action for the cardiovascular side of COVID-19. Eur Heart J 2020; 41: 1796-1797 doi:10.1093/eurheartj/ehaa301