Interferon induction, evasion, and paradoxical roles during SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused millions of deaths in the past two years. Although initially little was understood about this virus, recent research has significantly advanced and landed interferons (IFNs) in the spotlight. While Type I and III IFN have long been known as central to antiviral immunity, in the case of COVID-19 their role was initially controversial. However, the protective function of IFN is now well supported by the identification of human deficiencies in IFN responses as a predictor of disease severity. Here, we will review the cell types and pathways that lead to IFN production as well as the importance of IFN timing and location for disease outcome. We will further discuss the mechanisms that SARS-CoV-2 uses to evade IFN responses, and the current efforts to implement IFNs as therapeutics in the treatment of COVID-19. It is essential to understand the relationships between SARS-CoV-2 and IFN to better inform treatments that exploit IFN functions to alleviate COVID-19.

Automated summary

Recent research has revealed the important protective role of interferons (IFNs) against COVID-19, with human deficiencies in IFN responses serving as predictors of disease severity. The mechanisms by which SARS-CoV-2 evades IFN responses and the ongoing efforts to implement IFNs as therapeutics for COVID-19 are also discussed. Understanding the relationship between SARS-CoV-2 and IFN is crucial for informing treatments that exploit IFN functions to mitigate COVID-19.