Journal Article

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

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

2021

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antiviral agents / Antiviral drugs / Biology and life sciences / Biomedical research / Blood / Blood levels / Cardiology / Cell differentiation / Cell lines / Cell proliferation / Cell survival / Coronaviruses / COVID-19 / Cyclooxygenase-2 / Disease susceptibility / Enzymes / Epithelial cells / Epithelium / Evaluation / Funding / Health aspects / Health risks / Hematology / Immune response / Immune system / Immunological memory / Infections / Lung diseases / Lungs / Lymphocytes B / Males / Medical schools / Medicine and Health Sciences / Memory cells / Mortality / Oncology / Oxygenase / Pandemics / Pathology / Patients / Pax5 protein / Prostaglandin E2 / Prostaglandin endoperoxide synthase / Prostaglandins E / Risk analysis / Risk factors / Serum levels / Severe acute respiratory syndrome / Severe acute respiratory syndrome coronavirus 2 / Sex / Sports medicine / Vascular surgery / Veterinary medicine / Viral diseases / Viral infections / Virology / Zoonoses