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A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis

School of Biosciences, University of Kent, Canterbury CT2 7NZ, UK
Institute for Medical Virology, University Hospital, Goethe University Frankfurt am Main, 60596 Frankfurt am Main, Germany
Institute for Cardiovascular Regeneration, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
German Center for Cardiovascular Research (DZHK), 60590 Frankfurt am Main, Germany
Faculty for Biological Sciences, Goethe University, 60438 Frankfurt am Main, Germany
Institute of Biochemistry I, Faculty of Medicine, Goethe-University, 60590 Frankfurt am Main, Germany
German Center for Infection Research, DZIF, External Partner Site, 60590 Frankfurt am Main, Germany
Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Branch Translational Medicine und Pharmacology, 60590 Frankfurt am Main, Germany
Authors to whom correspondence should be addressed.
Equal contribution.
Academic Editor: Cristina Angeloni 
Curr. Issues Mol. Biol. 2021, 43(3), 1212-1225;
Received: 25 August 2021 / Revised: 16 September 2021 / Accepted: 17 September 2021 / Published: 22 September 2021
(This article belongs to the Section Molecular Medicine)
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. View Full-Text
Keywords: SARS-CoV-2; COVID-19; antiviral therapy; coronavirus; IAP; CD47; SIRPalpha SARS-CoV-2; COVID-19; antiviral therapy; coronavirus; IAP; CD47; SIRPalpha
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MDPI and ACS Style

McLaughlin, K.-M.; Bojkova, D.; Kandler, J.D.; Bechtel, M.; Reus, P.; Le, T.; Rothweiler, F.; Wagner, J.U.G.; Weigert, A.; Ciesek, S.; Wass, M.N.; Michaelis, M.; Cinatl, J., Jr. A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis. Curr. Issues Mol. Biol. 2021, 43, 1212-1225.

AMA Style

McLaughlin K-M, Bojkova D, Kandler JD, Bechtel M, Reus P, Le T, Rothweiler F, Wagner JUG, Weigert A, Ciesek S, Wass MN, Michaelis M, Cinatl J Jr.. A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis. Current Issues in Molecular Biology. 2021; 43(3):1212-1225.

Chicago/Turabian Style

McLaughlin, Katie-May, Denisa Bojkova, Joshua D. Kandler, Marco Bechtel, Philipp Reus, Trang Le, Florian Rothweiler, Julian U.G. Wagner, Andreas Weigert, Sandra Ciesek, Mark N. Wass, Martin Michaelis, and Jindrich Cinatl Jr. 2021. "A Potential Role of the CD47/SIRPalpha Axis in COVID-19 Pathogenesis" Current Issues in Molecular Biology 43, no. 3: 1212-1225.

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