Trends in Immunology
ReviewDual Nature of Type I Interferons in SARS-CoV-2-Induced Inflammation
Highlights
Evidence suggests that defects in responsiveness to type I interferons (IFN-I) s is of prime importance in determining the severity of coronavirus disease 2019 (COVID-19).
Genetic polymorphisms that decrease IFN-I production and the development of anti-IFN-I autoantibodies have been associated with more severe cases of COVID-19.
IFN-I is important to control virus infection, acting on both innate and adaptive arms of the immune response. Yet, it can also exacerbate inflammatory disease at late stages of respiratory virus infection.
Recent findings suggest conspicuous T cell and germinal center dysfunction in severe COVID-19.
A predominance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD8+ T cells is associated with mild COVID-19.
T cells play an important role in regulating the intensity of the proinflammatory response of the innate immune system.
The positive effects of IFN-I on the immune response may apply only during the initial stage of the immune response; once respiratory virus infection has been established, it may be too late for safe and effective IFN-I therapy, but prophylactic use of IFN-1 (or IFN-III) might have considerable potential, pending further investigations.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The ability of our cells to secrete type I interferons (IFN-Is) is essential for the control of virus replication and for effective antiviral immune responses; for this reason, viruses have evolved the means to antagonize IFN-I. Inhibition of IFN-I production is pronounced in SARS-CoV-2 infection, which can impair the adaptive immune response and exacerbate inflammatory disease at late stages of infection. However, therapeutic boosting of IFN-I offers a narrow time window for efficacy and safety. Here, we discuss how limits placed on IFN-I by SARS-CoV-2 shape the immune response and whether this might be countered with therapeutic approaches and vaccine design.