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Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease.
Ricke-Hoch, Melanie Stelling, Elisabeth Lasswitz, Lisa Gunesch, Antonia P Kasten, Martina Zapatero-Belinchón, Francisco J Brogden, Graham Gerold, Gisa Pietschmann, Thomas Montiel, Virginie
Ricke-Hoch, Melanie
Stelling, Elisabeth
Lasswitz, Lisa
Gunesch, Antonia P
Kasten, Martina
Zapatero-Belinchón, Francisco J
Brogden, Graham
Gerold, Gisa
Pietschmann, Thomas
Montiel, Virginie
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2021-08-04
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Abstract
he 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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PLoS One. 2021 Aug 4;16(8):e0255335. doi: 10.1371/journal.pone.0255335. PMID: 34347801.
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en
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1932-6203
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Attribution 4.0 International