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-hydroxyprostaglandin-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 Taxifolin 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.
- Ricke-Hoch, M.
- Stelling, E.
- Lasswitz, L.
- Gunesch, A. P.
- Kasten, M.
- Zapatero-Belinchón, 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.
- Mink, L.
- Scherr, M.
- Illig, T.
- Schambach, A.
- Pfeffer, T. J.
- Hilfiker, A.
- Haverich, A.
- Hilfiker-Kleiner, D.
