INTERFERICUS

During the COVID-19 pandemic, the emergence of SARS-CoV-2 variants of concern (VOC) has driven successive waves of infection, contributing to significant morbidity and mortality worldwide. Within-host viral diversity has been identified as a potential key factor driving the VOCs emergence (1). During SARS-CoV-2 infection, within-host genomic viral evolution has been mostly described during persistent infection in highly immunocompromised patients with altered adaptive immunity, such as patients suffering from cancer, under immunosuppressive treatment or having received a solid organ transplant (2-4). In addition to adaptative immunity, innate immune response - specifically the type I interferon (IFN-I) response - is also crucial to control viral replication. Recent observations indicate that critically ill patients infected with SARS-CoV-2 frequently exhibit impairment of the IFN-I response (5). Consequently, we hypothesized that an altered IFN-I response could lead to uncontrolled viral replication and contribute to within-host viral diversity. This study aimed to explore the association between innate immune response and the emergence of within-host SARS-CoV-2 genetic variants in a cohort of patients without known adaptative impairment, admitted to intensive care unit (ICU) for acute respiratory failure.