Antibodies against type-I Interferon: detection and association with severe clinical outcome in COVID-19 patients

Abstract Objectives Impairment of type I interferon (IFN-I) immunity has been reported in critically-ill COVID-19 patients. This defect can be explained in a subset of patients by the presence of circulating autoantibodies (auto-Abs) against IFN-I. We set out to improve the detection and the quantification of IFN-I auto-Abs in a cohort of critically-ill COVID-19 patients, in order to better evaluate the prevalence of these Abs as the pandemic progresses, and how they correlate with the clinical course of the disease. Methods The concentration of anti - IFN-α 2 Abs was determined in the serum of 84 critically-ill COVID-19 patients who were admitted to ICU in Hospices Civils de Lyon , France using a commercially available kit (Thermo-Fisher, Catalog #BMS217). Results A total of 21/84 (25%) critically-ill COVID-19 patients had circulating anti-IFN-α 2 Abs above cut-off (>34 ng.mL -1 ). Among them, 15/21 had Abs with neutralizing activity against IFN-α 2 , i . e . 15/84 (18%) of critically-ill patients. In addition, we noticed an impairment of the IFN-I response in the majority of patients with neutralizing anti-IFN-α 2 Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralizing anti-IFN-α 2 auto-Abs. We detected anti-IFN-α 2 auto-Abs in COVID-19 patients’ sera throughout their ICU stay. Finally, we also found auto-Abs against multiple subtypes of IFN-I including IFN-ω. Conclusions We reported that 18% of critically-ill COVID-19 patients were positive for IFN-I auto-Abs, confirming that the presence of these antibodies is associated with higher risk of developing a criticall COVID-19 form.