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dc.contributor.authorRicke-Hoch, Melanie
dc.contributor.authorStelling, Elisabeth
dc.contributor.authorLasswitz, Lisa
dc.contributor.authorGunesch, Antonia P
dc.contributor.authorKasten, Martina
dc.contributor.authorZapatero-Belinchón, Francisco J
dc.contributor.authorBrogden, Graham
dc.contributor.authorGerold, Gisa
dc.contributor.authorPietschmann, Thomas
dc.contributor.authorMontiel, Virginie
dc.contributor.authorBalligand, Jean-Luc
dc.contributor.authorFacciotti, Federica
dc.contributor.authorHirsch, Emilio
dc.contributor.authorGausepohl, Thomas
dc.contributor.authorElbahesh, Husni
dc.contributor.authorRimmelzwaan, Guus F
dc.contributor.authorHöfer, Anne
dc.contributor.authorKühnel, Mark P
dc.contributor.authorJonigk, Danny
dc.contributor.authorEigendorf, Julian
dc.contributor.authorTegtbur, Uwe
dc.contributor.authorMink, Lena
dc.contributor.authorScherr, Michaela
dc.contributor.authorIllig, Thomas
dc.contributor.authorSchambach, Axel
dc.contributor.authorPfeffer, Tobias J
dc.contributor.authorHilfiker, Andres
dc.contributor.authorHaverich, Axel
dc.contributor.authorHilfiker-Kleiner, Denise
dc.date.accessioned2021-10-01T12:42:18Z
dc.date.available2021-10-01T12:42:18Z
dc.date.issued2021-08-04
dc.identifier.citationPLoS One. 2021 Aug 4;16(8):e0255335. doi: 10.1371/journal.pone.0255335. PMID: 34347801.en_US
dc.identifier.pmid34347801
dc.identifier.doi10.1371/journal.pone.0255335
dc.identifier.urihttp://hdl.handle.net/10033/623055
dc.description.abstracthe 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.en_US
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleImpaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease.en_US
dc.typeArticleen_US
dc.identifier.eissn1932-6203
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.en_US
dc.identifier.journalPloS oneen_US
dc.source.volume16
dc.source.issue8
dc.source.beginpagee0255335
dc.source.endpage
dc.source.journaltitlePloS one
dc.source.countryInternational
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International