PLoS ONE (Jan 2021)

Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease

  • Melanie Ricke-Hoch,
  • Elisabeth Stelling,
  • Lisa Lasswitz,
  • Antonia P. Gunesch,
  • Martina Kasten,
  • Francisco J. Zapatero-Belinchón,
  • Graham Brogden,
  • Gisa Gerold,
  • Thomas Pietschmann,
  • Virginie Montiel,
  • Jean-Luc Balligand,
  • Federica Facciotti,
  • Emilio Hirsch,
  • Thomas Gausepohl,
  • Husni Elbahesh,
  • Guus F. Rimmelzwaan,
  • Anne Höfer,
  • Mark P. Kühnel,
  • Danny Jonigk,
  • Julian Eigendorf,
  • Uwe Tegtbur,
  • Lena Mink,
  • Michaela Scherr,
  • Thomas Illig,
  • Axel Schambach,
  • Tobias J. Pfeffer,
  • Andres Hilfiker,
  • Axel Haverich,
  • Denise Hilfiker-Kleiner

Journal volume & issue
Vol. 16, no. 8

Abstract

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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.