Interferon-alpha 2 Auto-antibodies in Convalescent Plasma Therapy for COVID-19

Purpose To study the effect of interferon-alpha 2 auto-antibodies (IFN-alpha 2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-alpha 2 Abs transfer during convalescent plasma treatment. Methods Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-alpha 2 Abs by ELISA and a pseudo virus-based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-alpha 2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-alpha 2 Abs and survival and viral load and whether serum IFN-alpha 2 Abs appeared after convalescent plasma transfusion. Results IFN-alpha 2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-alpha 2 Abs (13/164, 7.9%) neutralized levels of IFN-alpha 2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-alpha 2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-alpha 2. Neutralizing serum IFN-alpha 2 Abs were associated with delayed viral clearance from the respiratory tract. Conclusions IFN-alpha 2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-alpha 2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-alpha 2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.