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

Published version
Peer-reviewed

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Authors

Akbil, Bengisu 
Meyer, Tim 
Stubbemann, Paula 
Thibeault, Charlotte 
Staudacher, Olga 

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.

Description

Funder: Charité - Universitätsmedizin Berlin (3093)

Keywords

Autoantibodies, COVID-19, SARS-CoV-2, Type I interferon, Antibodies, Neutralizing, Autoantibodies, COVID-19, Critical Illness, Female, Humans, Interferon Type I, Interferon-alpha, Male, Oxygen, SARS-CoV-2

Journal Title

J Clin Immunol

Conference Name

Journal ISSN

0271-9142
1573-2592

Volume Title

42

Publisher

Springer Science and Business Media LLC
Sponsorship
DFG (158989968)