Publication date: Jun 24, 2023
A novel coronavirus now known as SARS-CoV-2 emerged during late 2019, possibly following zoonotic crossover from a coronavirus present in bats. This virus was identified as the pathogen responsible for the severe respiratory disease, coronavirus disease-19 (COVID-19), that as of May, 2023, has killed an estimated 6. 9 million people globally according to the World Health Organization. The interferon (IFN) response, the cornerstone of antiviral innate immunity, plays a key role in determining the outcome of infection by SARS-CoV-2. This review considers evidence that SARS-CoV-2 infection leads to IFN production; that virus replication is sensitive to IFN antiviral action; the molecular mechanisms by which the SARS-CoV-2 virus antagonizes IFN action; and how genetic variability of SARS-CoV-2 and the human host affects the IFN response at the level of IFN production or action or both. Taken together, current understanding suggests that deficiency of an effective IFN response is an important determinant underlying some cases of critical COVID-19 disease, and that IFNλ and IFNα/β have potential as therapeutics for treatment of SARS-CoV-2 infection.