TY  - JOUR
A1  - McLaughlin, Katie-May
A1  - Bojkova, Denisa
A1  - Kandler, Joshua D.
A1  - Bechtel, Marco
A1  - Reus, Philipp
A1  - Le, Thi Trang
A1  - Rothweiler, Florian
A1  - Wagner, Julian Uwe Gabriel
A1  - Weigert, Andreas
A1  - Ciesek, Sandra
A1  - Wass, Mark N.
A1  - Michaelis, Martin
A1  - Cinatl, Jindrich
T1  - A potential role of the CD47/SIRPalpha axis in COVID-19 pathogenesis
T2  - Current issues in molecular biology
N2  - The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.
KW  - SARS-CoV-2
KW  - COVID-19
KW  - antiviral therapy
KW  - coronavirus
KW  - IAP
KW  - CD47
KW  - SIRPalpha
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63393
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-633936
SN  - 1467-3045
N1  - This research was funded by the Frankfurter Stiftung für krebskranke Kinder; the Hilfe für krebskranke Kinder Frankfurt e.V.; the Deutsche Forschungsgemeinschaft (GRK 2336); the Hessen State Ministry of Higher Education, Research, and the Arts; the BBSRC (BB/V004174/1); and the World University Service (WUS). The APC was funded by Goethe University.
VL  - 43
IS  - 3
SP  - 1212
EP  - 1225
PB  - MDPI
CY  - Basel
ER  -