Expression of interferon-stimulated genes, but not polymorphisms in the interferon α/β receptor 2 gene, is associated with coronavirus disease 2019 mortality

Excessive inflammatory response is a hallmark of severe COVID-19. This study investigated the associations between interferon-stimulated genes (ISGs) expression, genetic variation in the interferon α/β receptor 2 (IFNAR2) gene, and COVID-19 mortality. We investigated 67 patients with moderate-to-severe COVID-19. Of them, 22 patients (32.8 %) died because of COVID-19. We examined the expression of ISGs in total RNA of peripheral whole blood. We observed a significant increase in the expression of all ISGs examined in non-surviving patients, indicating a heightened interferon type I signaling activation in non-survived patients. Subsequently, we analyzed whether the increase in ISGs expression was correlated with polymorphism within the <i>IFNAR2</i> gene. Intriguingly, no significant association was observed between <i>IFNAR2</i> gene polymorphism and COVID-19 mortality. Similarly, no association was noted between the IFNAR2 and ISGs expression levels. Overall, our data showed that higher ISGs expression, which presumably indicates heightened interferon type I activation, is associated with COVID-19 mortality.