Clinical characteristics of autoantibodies neutralizing type I interferons in patients with coronavirus disease 2019 across phases of severe acute respiratory syndrome coronavirus 2 circulation.

BACKGROUND

Autoantibodies neutralizing type I interferons (AAN-I-IFNs) have been identified as major risk factors for life-threatening coronavirus disease 2019 (COVID-19), particularly during the early phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread. However, because population immunity and circulating variants have changed substantially over time, the prevalence and clinical significance of AAN-I-IFNs in the later phases of SARS-CoV-2 circulation remain unclear.

METHODS

Hospitalized patients with COVID-19 diagnosed in Japan between September 2021 and January 2024 were analyzed. Neutralizing ability against IFN-α2, IFN-β, and IFN-ω was assessed by measuring phosphorylation of signal transducer and activator of transcription 1 in U937 cells. Autoantibodies binding to IFN-α2 were quantified by enzyme-linked immunosorbent assay. The clinical characteristics and disease severity were evaluated.

RESULTS

AAN-I-IFNs were detected in three of 211 patients (1.4%). Two of the 28 patients with critical COVID-19 (7.1%) carried AAN-I-IFNs. Even during the Omicron-dominant period, AAN-I-IFNs were associated with an increased risk of critical illness. In contrast, one middle-aged woman with an underlying autoimmune disease harbored AAN-I-IFNs but experienced a mild disease course, indicating heterogeneity in clinical outcomes among antibody-positive individuals.

CONCLUSIONS

AAN-I-IFNs continue to contribute to critical COVID-19 across different phases of SARS-CoV-2 circulation. However, the clinical spectrum of patients with AAN-I IFNs may expand beyond older men with critical illnesses to include middle-aged women with autoimmune diseases and milder disease presentations. Careful evaluation of underlying conditions and therapeutic interventions is warranted.