Although 80% of the patients remain asymptomatic or have a mild to moderate course of disease after infection with severe-acute-respiratory syndrome coronavirus 2 (SARS-CoV-2), up to 20% develop severe to critical pneumonia. Demographic and clinical risk factors including advanced age, male sex and pre-existing comorbidities contribute to progression towards a severe course of COVID-19. Furthermore, inborn errors leading to defective type I interferon signaling and presence of autoantibodies against type I IFN predispose patients to severe COVID-19. An interdisciplinary teaminvolving several departments at Charité – Universitätsmedizin Berlin, including Prof. Christine Goffinet, Institute of Virology, Dr. Christian Meisel, Institute of Medical Immunology and Labor Berlin, Prof. Horst von Bernuth, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, and Prof. Florian Kurth, Department of Infectious Diseases and Respiratory Medicine, proposes a clinically applicable strategy for early and rapid identification of type I IFN autoantibody-positive patients. In this study, sera of 430 COVID-19 patients from hospitals in Berlin, Bern, Freiburg and Heidelberg were collected and analyzed for the presence of type I IFN autoantibodies and their neutralizing activity. Neutralizing IFN autoantibodies were detected exclusively in critically affected patients and were associated with a lower probability of survival. Analysis of sera early post symptom onset and at the peak of the disease showed that the IFN autoantibodies were already present at an early stage of infection, potentially prior to the infection. Furthermore, analysis of clinical parameters demonstrated fever and oxygen requirement at hospital admission to be co-presenting with IFN autoantibody positivity. Reduced levels of IFN autoantibodies in patients that underwent therapeutic plasma exchange suggests the latter to be potentially beneficial toincrease the probability of survival of IFN autoantibody-positive patients. This study suggests that the IFN autoantibodies may serve as an early biomarker for severe COVID-19 and a routine screening to detect IFN autoantibodies is likely to benefitthese patients by implementation of subsequent clinical interventions.
Bengisu Akbil*, Tim Meyer*, Paula Stubbemann*, Charlotte Thibeault*, Olga Staudacher, Daniela Niemeyer, Jenny Jansen, Barbara Mühlemann B, Jan Doehn, Christoph Tabeling, Christian Nusshag, Cédric Hirzel, David Sökler Sanchez, Alexandra Nieters, Achim Lother, Daniel Duerschmied, Nils Schallner, Jan Nikolaus Lieberum, Dietrich August, Siegbert Rieg, Valeria Falcone, Hartmut Hengel, Uwe Kölsch, Nadine Unterwalder, Ralf-Harto Hübner, Terry C. Jones, Norbert Suttorp, Christian Drosten, Klaus Warnatz, Spinetti T, Schefold JC, Dörner T, Leif Erik Sander, Victor Max Corman, Uta Merle; Pa-COVID study Group, Florian Kurth#, Horst von Bernuth#, Christian Meisel#, Christine Goffinet#
Journal of Clinical Immunology, 2022. Link to freely accessible article: https://link.springer.com/article/10.1007/s10875-022-01252-2
This study was co-financed by the Innovationsfond of Labor Berlin, by the German Research Foundation and by BIH.
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