Anti-interferon α-antibodies in pediatric patients with COVID-19 and long COVID

The involvement of neutralizing antibodies against type I interferon (IFN-I) in the development of severe coronavirus disease 2019 (COVID-19) in adult patients has been well documented. However, the role of anti-IFN-α autoantibodies, especially non-neutralizing types, remains underexplored, especially in children. Our study aimed to determine the frequency of antibodies against IFN-α in children with COVID-19 and long COVID, as well as their potential role in the development of long COVID.

The study included 78 children aged 1 to 17 years with a documented history of COVID-19 from September 2022 to August 2023. All patients were divided into three groups: hospitalized with COVID-19, hospitalized with long COVID symptoms, and monitored in an outpatient care department for mild COVID-19 or symptoms of long COVID. Human anti-IFN-α antibodies were detected using enzyme-linked immunosorbent assay.

Binding anti-IFN-α antibodies were detected in 2/78 (2.6%) children with COVID-19 of varying severity. One patient with anti-IFN-α antibodies had comorbidities (obesity, allergic rhinitis) and critical COVID-19 pneumonia (SpO₂ - 80%), significant inflammatory changes (neutrophil-to-lymphocyte ratio: 18.8, C-reactive protein: 95.5 mg/l), and a high D-dimer level, and later developed long COVID symptoms. In the second case, COVID-19 in a 13-year-old girl without significant comorbidities was not severe, but leukopenia and lymphopenia were observed. Subsequently, she developed pronounced long COVID symptoms (fatigue, reduced appetite, insomnia, headache, decreased attention, difficulty concentrating, weight loss, tachycardia, dizziness), which persisted for up to 6 months after the acute infection. The detection rate of binding anti-IFN-α antibodies among hospitalized COVID-19 patients was 4%, compared to 25% among patients with severe/critical disease. Among children who developed long COVID symptoms, anti-IFN-α was found in 3.4%.

Further studies in larger cohorts are needed to assess the role of anti-IFN-α antibodies (both neutralizing and non-neutralizing) in the development of long COVID symptoms, to understand their clinical significance, and to examine their dynamics over time.