tetano
Editor, Senior Moderator
Respir Investig
. 2026 Jun 8;64(4):101459.
doi: 10.1016/j.resinv.2026.101459. Online ahead of print.
Clinical characteristics of autoantibodies neutralizing type I interferons in patients with coronavirus disease 2019 across phases of severe acute respiratory syndrome coronavirus 2 circulation
Haruka Sofuku[SUP] 1 [/SUP], Ami Aoki[SUP] 2 [/SUP], Natsumi Sakai[SUP] 3 [/SUP], Yuka Goto[SUP] 4 [/SUP], Hiroshi Ueno[SUP] 1 [/SUP], Kenjiro Shima[SUP] 1 [/SUP], Yosuke Kimura[SUP] 1 [/SUP], Makoto Kurokawa[SUP] 5 [/SUP], Katsuaki Asakawa[SUP] 6 [/SUP], Masaki Terada[SUP] 6 [/SUP], Yoshinari Tanabe[SUP] 4 [/SUP], Toshinori Takada[SUP] 7 [/SUP], Toshiyuki Koya[SUP] 1 [/SUP], Toshiaki Kikuchi[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Autoantibodies neutralizing type I interferons; Coronavirus disease 2019 (COVID-19); Host immunity; Omicron.
. 2026 Jun 8;64(4):101459.
doi: 10.1016/j.resinv.2026.101459. Online ahead of print.
Clinical characteristics of autoantibodies neutralizing type I interferons in patients with coronavirus disease 2019 across phases of severe acute respiratory syndrome coronavirus 2 circulation
Haruka Sofuku[SUP] 1 [/SUP], Ami Aoki[SUP] 2 [/SUP], Natsumi Sakai[SUP] 3 [/SUP], Yuka Goto[SUP] 4 [/SUP], Hiroshi Ueno[SUP] 1 [/SUP], Kenjiro Shima[SUP] 1 [/SUP], Yosuke Kimura[SUP] 1 [/SUP], Makoto Kurokawa[SUP] 5 [/SUP], Katsuaki Asakawa[SUP] 6 [/SUP], Masaki Terada[SUP] 6 [/SUP], Yoshinari Tanabe[SUP] 4 [/SUP], Toshinori Takada[SUP] 7 [/SUP], Toshiyuki Koya[SUP] 1 [/SUP], Toshiaki Kikuchi[SUP] 1 [/SUP]
Affiliations
- PMID: 42259185
- DOI: 10.1016/j.resinv.2026.101459
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.
Keywords: Autoantibodies neutralizing type I interferons; Coronavirus disease 2019 (COVID-19); Host immunity; Omicron.