Interferon system deficiencies exacerbating severe pandemic virus infections

Pandemics are caused by novel pathogens to which pre-existing antibody immunity is lacking. Under these circumstances, the body must rely on innate interferon-mediated defenses to limit pathogen replication and allow development of critical humoral protection. Here, we highlight studies on disease susceptibility during H1N1 influenza and COVID-19 (SARS-CoV-2) pandemics. An emerging concept is that genetic and non-genetic deficiencies in interferon system components lead to uncontrolled virus replication and severe illness in a subset of people. Intriguingly, new findings suggest that individuals with autoantibodies neutralizing the antiviral function of interferon are at increased risk of severe COVID-19. We discuss key questions surrounding how such autoantibodies develop and function, as well as the general implications of diagnosing interferon deficiencies for personalized therapies.

Automated summary

Pandemics are caused by novel pathogens due to lack of pre-existing antibody immunity. Studies show that deficiencies in the interferon system components can lead to uncontrolled virus replication and severe illness in some individuals, while autoantibodies neutralizing interferon's antiviral function may increase the risk of severe COVID-19.