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


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.

SUBMITTER: Akbil B 

PROVIDER: S-EPMC9069123 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Akbil Bengisu B   Meyer Tim T   Stubbemann Paula P   Thibeault Charlotte C   Staudacher Olga O   Niemeyer Daniela D   Jansen Jenny J   Mühlemann Barbara B   Doehn Jan J   Tabeling Christoph C   Nusshag Christian C   Hirzel Cédric C   Sanchez David Sökler DS   Nieters Alexandra A   Lother Achim A   Duerschmied Daniel D   Schallner Nils N   Lieberum Jan Nikolaus JN   August Dietrich D   Rieg Siegbert S   Falcone Valeria V   Hengel Hartmut H   Kölsch Uwe U   Unterwalder Nadine N   Hübner Ralf-Harto RH   Jones Terry C TC   Suttorp Norbert N   Drosten Christian C   Warnatz Klaus K   Spinetti Thibaud T   Schefold Joerg C JC   Dörner Thomas T   Sander Leif Erik LE   Corman Victor M VM   Merle Uta U   Kurth Florian F   von Bernuth Horst H   Meisel Christian C   Goffinet Christine C  

Journal of clinical immunology 20220505 6


<h4>Purpose</h4>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.<h4>Methods</h4>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-in  ...[more]

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