AUTHOR=Framil Mario , García-Serrano Lydia , Morandeira Francisco , Luchoro Juan Francisco , Antolí Arnau , Gomez-Vazquez Jose Luis , Sierra-Fortuny Àngels , Solanich Xavier 

TITLE=Non-neutralizing anti-type I interferon autoantibodies could increase thrombotic risk in critical COVID-19 patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1556731

DOI=10.3389/fimmu.2025.1556731

ISSN=1664-3224

ABSTRACT=During the COVID-19 pandemic, approximately 15% of patients with severe COVID-19 pneumonia were reported to have neutralizing anti-type I interferon (IFN) autoantibodies, which impaired the antiviral response and led to a poorer prognosis. However, the physiological impact of non-neutralizing autoantibodies remains unclear. In our cohort of COVID-19 patients admitted to intensive care, the presence of non-neutralizing anti-type I IFN autoantibodies increased the risk of thrombotic complications, likely via a cytokine carrier mechanism, prolonging the half-life of cytokines and dysregulating vascular endothelial function. Previous studies have associated non-neutralizing anti-type I IFN autoantibodies with an increased risk of cardiovascular complications in autoimmune diseases like systemic lupus erythematosus, but their relevance in infectious diseases remains uncertain. Stratifying anti-type I IFN autoantibodies based on their neutralizing capacity may have clinical significance not only in terms of susceptibility to infectious diseases but also in predicting cardiovascular and thrombotic events.