Autoantibodies neutralizing type I interferons in COVID-19 patients from southern Brazil

Inborn errors of type I IFN (IFN-I) immunity and neutralizing autoantibodies (auto-Abs) against IFN-I (AAN-I-IFNs) impair antiviral immunity and underlie critical COVID-19. Their impact on disease severity in different populations, such as Latin American populations, remains to be better understood. This study assessed the presence of AAN-I-IFNs (anti-IFN-α2, anti-IFN-ω, and anti-IFN-β) in a cohort of 458 COVID-19 patients from southern Brazil, stratified as mild (n = 224) versus non-mild (n = 234), or survivors (n = 369) versus deceased (n = 89). AAN-I-IFNs were detected in 17 patients (3.7%), with increasing prevalence across disease severity, present in one (0.4%) mild case and 16 (6.8%) hospitalized cases (P = 0.006); and eight (2.2%) survivors and nine (10.1%) deceased cases (P = 0.008). Anti-IFN-α2 and anti-IFN-ω auto-Abs were most frequently detected, while anti-IFN-β auto-Abs were found in one patient. Our findings highlight the role of AAN-I-IFNs underlying COVID-19 severity in a southern Brazilian population.