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Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies.
Akbil, Bengisu; Meyer, Tim; Stubbemann, Paula; Thibeault, Charlotte; Staudacher, Olga; Niemeyer, Daniela; Jansen, Jenny; Mühlemann, Barbara; Doehn, Jan; Tabeling, Christoph; Nusshag, Christian; Hirzel, Cédric; Sanchez, David Sökler; Nieters, Alexandra; Lother, Achim; Duerschmied, Daniel; Schallner, Nils; Lieberum, Jan Nikolaus; August, Dietrich; Rieg, Siegbert; Falcone, Valeria; Hengel, Hartmut; Kölsch, Uwe; Unterwalder, Nadine; Hübner, Ralf-Harto; Jones, Terry C; Suttorp, Norbert; Drosten, Christian; Warnatz, Klaus; Spinetti, Thibaud; Schefold, Joerg C; Dörner, Thomas; Sander, Leif Erik; Corman, Victor M; Merle, Uta; Kurth, Florian; von Bernuth, Horst; Meisel, Christian; Goffinet, Christine.
  • Akbil B; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
  • Meyer T; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Stubbemann P; Labor Berlin GmbH, Department of Immunology, Charité - Universitätsmedizin Berlin, Sylter Str. 2, 13353, Berlin, Germany.
  • Thibeault C; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Staudacher O; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Niemeyer D; Labor Berlin GmbH, Department of Immunology, Charité - Universitätsmedizin Berlin, Sylter Str. 2, 13353, Berlin, Germany.
  • Jansen J; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Mühlemann B; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
  • Doehn J; DZIF German Centre for Infection Research (DZIF), Partner Site Charité, 10117, Berlin, Germany.
  • Tabeling C; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
  • Nusshag C; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Hirzel C; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
  • Sanchez DS; DZIF German Centre for Infection Research (DZIF), Partner Site Charité, 10117, Berlin, Germany.
  • Nieters A; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Lother A; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Duerschmied D; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Schallner N; Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
  • Lieberum JN; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • August D; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Rieg S; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Falcone V; University Medical Center Freiburg and Faculty of Medicine, University of Freiburg, Center for Biobanking, FREEZE-Biobank, Freiburg, Germany.
  • Hengel H; Cardiology and Medical Intensive Care, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Kölsch U; Cardiology and Medical Intensive Care, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Unterwalder N; Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Freiburg, Germany.
  • Hübner RH; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Jones TC; Department of Anesthesiology and Critical Care, Medical Center - University of Freiburg, Freiburg, Germany.
  • Suttorp N; Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Drosten C; Division of Infectious Diseases, Department of Medicine II, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106, Freiburg, Germany.
  • Warnatz K; Division of Infectious Diseases, Department of Medicine II, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106, Freiburg, Germany.
  • Spinetti T; Institute of Virology, Freiburg University Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
  • Schefold JC; Institute of Virology, Freiburg University Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
  • Dörner T; Labor Berlin GmbH, Department of Immunology, Charité - Universitätsmedizin Berlin, Sylter Str. 2, 13353, Berlin, Germany.
  • Sander LE; Labor Berlin GmbH, Department of Immunology, Charité - Universitätsmedizin Berlin, Sylter Str. 2, 13353, Berlin, Germany.
  • Corman VM; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Merle U; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Kurth F; DZIF German Centre for Infection Research (DZIF), Partner Site Charité, 10117, Berlin, Germany.
  • von Bernuth H; Centre for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing St, Cambridge, CB2 3EJ, UK.
  • Meisel C; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
  • Goffinet C; Institute of Virology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Charitéplatz 1, 10117, Berlin, Germany.
J Clin Immunol ; 2022 May 05.
Article in English | MEDLINE | ID: covidwho-1820957
ABSTRACT

PURPOSE:

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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study / Prognostic study / Risk factors Language: English Year: 2022 Document Type: Article Affiliation country: S10875-022-01252-2

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study / Prognostic study / Risk factors Language: English Year: 2022 Document Type: Article Affiliation country: S10875-022-01252-2