ABSTRACT
The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds prostaglandin E2 (PGE2) blood levels elevated in COVID-19 patients with positive correlation 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-lung-precision-slices infected with SARS-CoV-2 display upregulated COX-2. PGE2 in serum of COVID-19 patients lowers the expression of Paired-Box-Protein-Pax-5 (PAX5), a master regulator of B-cell survival, proliferation and differentiation, in both human and mouse pre-B-cells, while the PGE2 inhibitor taxifolin directly reduces SARS-CoV-2-induced PGE2 production and attenuates viral replication. Risk-factors for severe disease courses, i.e. older age, male sex and air pollution are associated with higher PGE2 production and lower PAX5 expression in pre-B-cells. Since PGE2 acts broadly immunosuppressive its elevation might reduce the early anti-viral defense and its inhibition may therefore reduce severe disease courses.