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Trends Microbiol
. 2021 Mar 20;S0966-842X(21)00060-3.
doi: 10.1016/j.tim.2021.03.001. Online ahead of print.
Interferon system deficiencies exacerbating severe pandemic virus infections
Silke Stertz 1 , Benjamin G Hale 2
Affiliations
- PMID: 33757684
- PMCID: PMC7980109
- DOI: 10.1016/j.tim.2021.03.001
Abstract
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.
Keywords: COVID-19; autoantibodies; disease severity; host genetics; influenza; interferon; pandemic virus.