Purpose To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment. Methods Sera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 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-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion. Results IFN-α2 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-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract. Conclusions IFN-α2 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-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01168-3.
【저자키워드】 COVID-19, convalescent plasma, SARS-CoV-2, Interferon alpha, Auto-antibodies, 【초록키워드】 disease severity, interferon, Respiratory illness, Sex, risk, viral clearance, ELISA, serum, survival, Viral, Critically ill, Neutralization assay, Viral load, sera, Patient, plasma, age, ICU Patients, respiratory illnesses, Neutralizing, respiratory tract, respiratory, longitudinal, COVID-19 patients, Donor, association, Human plasma, Concentration, Analysis, COVID-19 patient, physiological, critically ill COVID-19 patients, supplementary material, IFN-α2, proportions, transfer, healthy controls, convalescent plasma treatment, positive, Longitudinal analyses, Effect, ICU patient, neutralized, Result, tested, performed, proportion, condition, determine, auto-antibody, not neutralize, virological outcome,