Autoantibodies against type I interferons are a prominent feature in SARS-CoV-2 fatal disease and hospitalization

Background Autoantibodies have been implicated as key players in COVID-19 pathogenesis, with evidence of impacting disease severity and poor outcomes. Methods We analyzed autoantibody profiles in 435 PCR-confirmed COVID-19 patients in Manaus, Brazil, comparing hospitalized (263) and non-hospitalized (172) individuals, and 37 healthy controls. Twenty autoantibodies and SARS-CoV-2-specific IgA/IgG antibodies were measured using multiplex Luminex® assays from plasma samples collected on days 1, 7, 14, and 28. Results Hospitalized patients had significantly higher levels of autoantibodies targeting ACE2, MPO, IFNΩ, IFNα1 and IFNα2 at baseline, with 127 hospitalized patients positive for IFNα1, 161 for IFNα2 and 68 for IFNΩ. Longitudinal analysis revealed progressively increasing levels of anti-ACE2, B2G1, C1q, IFNα1, IFNα2, PADI4, PF4 and PR3 autoantibodies in hospitalized patients, however the neutralizing capacity of IFNs were not investigated. Survival analysis showed that elevated type I IFN autoantibodies correlated with reduced survival (p=0.023). Stronger correlations between autoantibodies and SARS-CoV-2 IgA/IgG were found in severe cases. Conclusions In this cohort, autoantibodies were linked to COVID-19 severity and mortality, indicating their potential as biomarkers for patient risk stratification and therapeutic targets. Further research is needed to explore their impact in long-term immune dysregulation and post-acute sequelae in COVID-19 survivors.