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dc.contributor.authorHolter, Jan Cato
dc.contributor.authorPischke, Soeren
dc.contributor.authorde Boer, Eline
dc.contributor.authorLind, Andreas
dc.contributor.authorJenum, Synne
dc.contributor.authorHolten, Aleksander Rygh
dc.contributor.authorTonby, Kristian
dc.contributor.authorBarratt-Due, Andreas
dc.contributor.authorSokolova, Marina
dc.contributor.authorSchjalm, Camilla
dc.contributor.authorChaban, Viktoriia
dc.contributor.authorKolderup, Anette
dc.contributor.authorTran, Trung
dc.contributor.authorTollefsrud Gjølberg, Torleif
dc.contributor.authorSkeie, Linda Gail
dc.contributor.authorHesstvedt, Liv
dc.contributor.authorOrmåsen, Vidar
dc.contributor.authorFevang, Børre
dc.contributor.authorAustad, Cathrine
dc.contributor.authorMuller, Karl Erik
dc.contributor.authorFladeby, Cathrine
dc.contributor.authorHolberg-Petersen, Mona
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorMüller, Fredrik
dc.contributor.authorAukrust, Pål
dc.contributor.authorDudman, Susanne Gjeruldsen
dc.contributor.authorUeland, Thor
dc.contributor.authorAndersen, Jan Terje
dc.contributor.authorLund-Johansen, Fridtjof
dc.contributor.authorHeggelund, Lars
dc.contributor.authorDyrhol-Riise, Anne Ma
dc.contributor.authorMollnes, Tom Eirik
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America. 2020, 117 (40), 25018-25025.en_US
dc.description.abstractRespiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.en_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleSystemic complement activation is associated with respiratory failure in COVID-19 hospitalized patientsen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.source.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.description.localcodeCopyright © 2020 the Author(s). Published by PNAS. Open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).en_US

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