Viral diversity news

Dr. David Bussy, intensivist at the Department of Intensive Care Medicine at Croix-Rousse University Hospital, and Kylian Trepat, PhD candidate, contributed to the article “Case-based evidence links increased SARS-CoV-2 diversity to impaired IFN-I response in severe COVID-19”, published in July 2025 in the Journal of Human Immunity – https://doi.org/10.70962/jhi.20250019

Intra-host viral diversity is a key factor in the emergence of SARS-CoV-2 variants, a phenomenon particularly pronounced in immunocompromised patients. Prolonged viral shedding promotes the accumulation of mutations and thereby increases intra-host viral diversity. The initial control of viral replication largely depends on the antiviral response mediated by type I interferons (IFN-I). Several studies have demonstrated that impairment of this response, frequently observed in severe forms of viral respiratory infections, can lead to uncontrolled replication and, consequently, could contribute to greater intra-host viral diversification.

The aim of the study was to assess whether impaired IFN-I responses may promote the emergence of intra-host viral diversity. Within a prospective clinical cohort, one patient was identified who exhibited exceptionally high intra-host viral diversity. This observation was associated with the presence of autoantibodies neutralizing IFN-β, thereby compromising the antiviral response.
These findings strengthen the hypothesis that impaired IFN-I responses—particularly when mediated by anti-IFN-I autoantibodies—contribute to the generation and persistence of intra-host viral diversity, with direct implications for understanding the emergence of viral variants.