Type I interferons and SARS-CoV-2: from cells to organisms

Abstract

Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro. In various animal species infected in vivo, type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.

Figure 1

Life-threatening COVID-19 can be caused in Humans by inborn errors of type I IFN immunity or autoantibodies neutralizing type I IFNs. Both mechanisms interfering with type I IFN immunity in respiratory epithelial cells and blood plasmacytoid dendritic cells. SARS-CoV-2 can replicate in respiratory epithelial cells (REC), but not in pDC which is why the responsive pathway is only shown in REC, where anti-viral ISG will matter, while the self-amplification loop of type I IFN does probably also operate in pDCs. Monogenic inborn errors of type I IFN immunity are shown in red. Auto-Abs to type I IFNs are shown in red. SARS-CoV-2 proteins which can inhibit proteins of the type I IFN pathway are shown in blue. Type I IFNs are shown in blue circles. IFN: interferon; Auto-Ab: autoantibody, ISGs: interferon-stimulated genes.

Figure 2

Odds Ratios for critical disease in SARS-CoV-2-infected individuals with auto-Abs against type I IFNs. Odds ratios (OR) and P-values were estimated by means of Firth’s bias-corrected logistic regression.