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

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-alpha(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 of 84 (25%) critically ill COVID-19 patients had circulating anti-IFN-alpha(2) Abs above cut-off (> 34 ng mL(-1)). Among them, 15 of 21 had Abs with neutralising activity against IFN-alpha(2), that is 15 of 84 (18%) critically ill patients. In addition, we noticed an impairment of the IFN-I response in the majority of patients with neutralising anti-IFN-alpha(2) Abs. There was no significant difference in the clinical characteristics or outcome of with or without neutralising anti-IFN-alpha(2) auto-Abs. We detected anti-IFN-alpha(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-omega. Conclusions We reported that 18% of critically ill COVID-19 patients were positive for IFN-I auto-Abs, whereas all mild COVID-19 patients were negative, confirming that the presence of these antibodies is associated with a higher risk of developing a critical COVID-19 form.