Selected article for: "age increase and old age"
Author: Ricke-Hoch, Melanie; Stelling, Elisabeth; Lasswitz, Lisa; Gunesch, Antonia P.; Kasten, Martina; Zapatero-Belinchón, Francisco J.; Brogden, Graham; Gerold, Gisa; Pietschmann, Thomas; Montiel, Virginie; Balligand, Jean-Luc; Facciotti, Federica; Hirsch, Emilio; Gausepohl, Thomas; Elbahesh, Husni; Rimmelzwaan, Guus F.; Höfer, Anne; Kühnel, Mark P.; Jonigk, Danny; Eigendorf, Julian; Tegtbur, Uwe; Mink, Lena; Scherr, Michaela; Illig, Thomas; Schambach, Axel; Pfeffer, Tobias J.; Hilfiker, Andres; Haverich, Axel; Hilfiker-Kleiner, Denise
Title: Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease
  • Cord-id: 4t9brkx0
  • Document date: 2021_8_4
    • ID: 4t9brkx0
    Snippet: 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 epith
    Document: 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.

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