Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease
(2021) PLoS One — Vol. 16, n° 8, p. e0255335 [1-24] (2021)
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- The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglan- din-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS- CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxi- folin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.
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Lasswitz, L., Gunesch, A. P., Kasten, M., Zapatero-Belinchon, F. J., Brogden, G., Gerold, G., Pietschmann, T., Montiel, V., Balligand, J.-L., Facciotti, F., Hirsch, E., Gausepohl, T., Elbahesh, H., Rimmelzwaan, G. F., Höfer, A., Kühnel, M. P., Jonigk, D., Eigendorf, J., Tegtbur, U., et al. (2021). Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease. PLoS One, 16(8), e0255335 [1-24]. https://doi.org/10.1371/journal.pone.0255335 (Original work published 2021)