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dc.contributor.authorAkbil, Bengisu
dc.contributor.authorMeyer, Tim
dc.contributor.authorStubbemann, Paula
dc.contributor.authorThibeault, Charlotte
dc.contributor.authorStaudacher, Olga
dc.contributor.authorNiemeyer, Daniela
dc.contributor.authorJansen, Jenny
dc.contributor.authorMühlemann, Barbara
dc.contributor.authorDoehn, Jan
dc.contributor.authorTabeling, Christoph
dc.contributor.authorNusshag, Christian
dc.contributor.authorHirzel, Cédric
dc.contributor.authorSanchez, David Sökler
dc.contributor.authorNieters, Alexandra
dc.contributor.authorLother, Achim
dc.contributor.authorDuerschmied, Daniel
dc.contributor.authorSchallner, Nils
dc.contributor.authorLieberum, Jan Nikolaus
dc.contributor.authorAugust, Dietrich
dc.contributor.authorRieg, Siegbert
dc.contributor.authorFalcone, Valeria
dc.contributor.authorHengel, Hartmut
dc.contributor.authorKölsch, Uwe
dc.contributor.authorUnterwalder, Nadine
dc.contributor.authorHübner, Ralf-Harto
dc.contributor.authorJones, Terry C
dc.contributor.authorSuttorp, Norbert
dc.contributor.authorDrosten, Christian
dc.contributor.authorWarnatz, Klaus
dc.contributor.authorSpinetti, Thibaud
dc.contributor.authorSchefold, Joerg C
dc.contributor.authorDörner, Thomas
dc.contributor.authorSander, Leif Erik
dc.contributor.authorCorman, Victor M
dc.contributor.authorMerle, Uta
dc.contributor.authorPa-COVID study Group
dc.contributor.authorKurth, Florian
dc.contributor.authorvon Bernuth, Horst
dc.contributor.authorMeisel, Christian
dc.contributor.authorGoffinet, Christine
dc.date.accessioned2022-06-07T08:16:08Z
dc.date.available2022-06-07T08:16:08Z
dc.date.issued2022-05-05
dc.identifier.issn0271-9142
dc.identifier.other35511314
dc.identifier.otherPMC9069123
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/337822
dc.descriptionFunder: Charité - Universitätsmedizin Berlin
dc.description.abstractPURPOSE: Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable strategy for early identification of IFN-AAB-positive patients for potential subsequent clinical interventions. METHODS: We analyzed sera of 430 COVID-19 patients from four hospitals for presence of IFN-AABs by ELISA. Binding specificity and neutralizing activity were evaluated via competition assay and virus-infection-based neutralization assay. We defined clinical parameters associated with IFN-AAB positivity. In a subgroup of critically ill patients, we analyzed effects of therapeutic plasma exchange (TPE) on the levels of IFN-AABs, SARS-CoV-2 antibodies and clinical outcome. RESULTS: The prevalence of neutralizing AABs to IFN-α and IFN-ω in COVID-19 patients from all cohorts was 4.2% (18/430), while being undetectable in an uninfected control cohort. Neutralizing IFN-AABs were detectable exclusively in critically affected (max. WHO score 6-8), predominantly male (83%) patients (7.6%, 18/237 for IFN-α-AABs and 4.6%, 11/237 for IFN-ω-AABs in 237 patients with critical COVID-19). IFN-AABs were present early post-symptom onset and at the peak of disease. Fever and oxygen requirement at hospital admission co-presented with neutralizing IFN-AAB positivity. IFN-AABs were associated with lower probability of survival (7.7% versus 80.9% in patients without IFN-AABs). TPE reduced levels of IFN-AABs in three of five patients and may increase survival of IFN-AAB-positive patients compared to those not undergoing TPE. CONCLUSION: IFN-AABs may serve as early biomarker for the development of severe COVID-19. We propose to implement routine screening of hospitalized COVID-19 patients for rapid identification of patients with IFN-AABs who most likely benefit from specific therapies.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 8102137
dc.sourceessn: 1573-2592
dc.titleEarly and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies.
dc.typeArticle
dc.date.updated2022-06-07T08:16:08Z
prism.publicationNameJ Clin Immunol
dc.identifier.doi10.17863/CAM.85231
dcterms.dateAccepted2022-03-14
rioxxterms.versionofrecord10.1007/s10875-022-01252-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidKurth, Florian [0000-0002-3807-473X]
dc.contributor.orcidMeisel, Christian [0000-0003-0222-991X]
dc.contributor.orcidGoffinet, Christine [0000-0002-3959-004X]
dc.identifier.eissn1573-2592
cam.issuedOnline2022-05-05


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