Ricke-Hoch M, Stelling E, Lasswitz L, Gunesch AP, Kasten M, Zapatero-Belinchón FJ, Brogden G, Gerold G, Pietschmann T, Montiel V, Balligand JL, Facciotti F, Hirsch E, Gausepohl T, Elbahesh H, Rimmelzwaan GF, Höfer A, Kühnel MP, Jonigk D, Eigendorf J, Tegtbur U, Mink L, Scherr M, Illig T, Schambach A, Pfeffer TJ, Hilfiker A, Haverich A, Hilfiker-Kleiner D
PLoS One 16 (8) e0255335 [2021-08-04; online 2021-08-04]
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.