A commentary of “Type I interferon deficiency can lead to severe COVID-19” in 10 remarkable discoveries from 2020 in Nature

In two articles published in Science online in September 2020, Zhang et al. [1] and Bastard et al. [2] elucidated a key factor in the progression to severe COVID-19; namely, a deficiency in interferon, especially type I interferon (IFN I). This deficiency might be caused by diverse reasons such as genetic mutations of genes encoding key antiviral signaling molecules, or the ‘neutralization’ of IFN I by endogenous antibodies. How does IFN I deficiency cause severe, life-threatening COVID-19? The most straightforward explanation is that such deficiency allows uncontrolled virus replication and spread. IFN I deficiency may also have other impacts on immune system function. Individuals with mutations in the IFN-I-induced signaling pathways may benefit from interferon therapies. In addition, individuals with neutralizing antibodies against IFN-α and IFN-ω may also benefit from other types of interferons provided in the therapy, such as IFN-β and IFN-λ.