Adding to the essential role of IFN in early antiviral response, two recent studies have shown that genetic changes are associated with inadequate IFN response. In the first study, the presence of IFN neutralizing auto-antibodies found in patients who exhibited more severe disease condition (Bastard et al., 2020). These auto-antibodies were more prevalent in men than women, that partly explains the susceptibility of men to COVID-19. None of the asymptomatic or mild cases had detectable auto-antibodies. In the other study, mutations in 13 key genes implicated in TLR3- and IRF7-dependent exhibit loss-of-function (Zhang Q. et al., 2020). Patients or the cells derived from these patients with loss-of-function in these genes had inadequate IFN response and vulnerable to SARS-CoV-2 infection. In a similar study on four patients with severe disease symptoms, the whole exome-sequencing revealed loss-of-function of TLR7, which is essentially involved in IFN signaling. These patients exhibited decreased expression of IRF7, IFNB1, and ISG15, along with reduced production of IFN-γ (Van Der Made et al., 2020). Thus, impaired IFN signaling, mediated either directly by the virus by interfering at various steps in the IFN signaling, or genetic predisposition of some individuals to inadequate IFN response and presence of IFN neutralizing auto-antibodies are some of the significant factors which determine the COVID-19 disease severity. The dysfunctional IFN response in conjunction with other innate and adaptive immune responses may thus decide the path to recovery or progression to more severe form of the disease (Hadjadj et al., 2020). Impaired type I interferon activity and exacerbated inflammatory responses in severe COVID-19 patients (Hadjadj et al., 2020; Park and Iwasaki, 2020). A comprehensive understanding of the molecular mechanisms by which SARS-CoV-2 causes impaired IFN response is still lacking, and future studies may help us to understand this.