Endothel, vaskuläre Funktion und 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?

• In der hyperinflammatorischen Phase der COVID-19-Erkrankung kommt es zu einer massiven Zytokinfreisetzung und zu sekundären Organschäden.

• 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.

• Ein systemischer prothrombotischer Status, Mikroangiopathien und eine Endotheliitis selbst sind Erklärungsansätze für die schwere mikrovaskuläre Störung bei schweren Verläufen einer COVID-19-Erkrankung.

Schlüsselwörter

Endothel - vaskuläre Funktion - SARS-CoV-2 - ACE-2

Key words

endothelium - vascular function - SARS-CoV-2 - ACE 2

Publication History

Article published online:
17 December 2020

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