Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies
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Published:2022-05-05
Issue:6
Volume:42
Page:1111-1129
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ISSN:0271-9142
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Container-title:Journal of Clinical Immunology
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language:en
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Short-container-title:J Clin Immunol
Author:
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 FlorianORCID, von Bernuth Horst, Meisel ChristianORCID, Goffinet ChristineORCID,
Abstract
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.
Funder
DFG Charité - Universitätsmedizin Berlin
Publisher
Springer Science and Business Media LLC
Subject
Immunology,Immunology and Allergy
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