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Open Access 05-05-2022 | SARS-CoV-2 | Original Article

Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Authors: Bengisu Akbil, Tim Meyer, Paula Stubbemann, Charlotte Thibeault, Olga Staudacher, Daniela Niemeyer, Jenny Jansen, Barbara Mühlemann, 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, Thibaud Spinetti, Joerg C. Schefold, Thomas Dörner, Leif Erik Sander, Victor M. Corman, Uta Merle, Florian Kurth, Horst von Bernuth, Christian Meisel, Christine Goffinet, Pa-COVID study Group

Published in: Journal of Clinical Immunology | Issue 6/2022

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.

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Title: Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies
Authors: Bengisu Akbil
Tim Meyer
Paula Stubbemann
Charlotte Thibeault
Olga Staudacher
Daniela Niemeyer
Jenny Jansen
Barbara Mühlemann
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
Thibaud Spinetti
Joerg C. Schefold
Thomas Dörner
Leif Erik Sander
Victor M. Corman
Uta Merle
Florian Kurth
Horst von Bernuth
Christian Meisel
Christine Goffinet
Pa-COVID study Group
Publication date: 05-05-2022
Publisher: Springer US
Keywords: SARS-CoV-2
COVID-19
Interferon
Published in: Journal of Clinical Immunology / Issue 6/2022
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-022-01252-2

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Abstract

Purpose

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Conclusion

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