Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies
Creators: name: Akbil, Bengisu
name: Meyer, Tim
name: Stubbemann, Paula
name: Thibeault, Charlotte
name: Staudacher, Olga
name: Niemeyer, Daniela
name: Jansen, Jenny
name: Mühlemann, Barbara
name: Doehn, Jan
name: Tabeling, Christoph
name: Nusshag, Christian
name: Hirzel, Cédric
name: Sanchez, David Sökler
name: Nieters, Alexandra
name: Lother, Achim
name: Duerschmied, Daniel
name: Schallner, Nils
name: Lieberum, Jan Nikolaus
name: August, Dietrich
name: Rieg, Siegbert
name: Falcone, Valeria
name: Hengel, Hartmut
name: Kölsch, Uwe
name: Unterwalder, Nadine
name: Hübner, Ralf-Harto
name: Jones, Terry C.
name: Suttorp, Norbert
name: Drosten, Christian
name: Warnatz, Klaus
name: Spinetti, Thibaud
name: Schefold, Joerg C.
name: Dörner, Thomas
name: Sander, Leif Erik
name: Corman, Victor M.
name: Merle, Uta
name: Kurth, Florian
name: Von Bernuth, Horst
name: Meisel, Christian
name: Goffinet, Christine
name: Pa-COVID Study Group
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2022
Subjects: subject: COVID-19
subject: SARS-CoV-2
subject: Type I interferon
subject: Autoantibodies
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

description: 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-alpha and IFN-omega 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-alpha-AABs and 4.6%, 11/237 for IFN-omega-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.