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 IFNAR2 gene. Intriguingly, no significant association was observed between IFNAR2 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.