Inherited and acquired errors of type I interferon immunity govern susceptibility to COVID-19 and multisystem inflammatory syndrome in children

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic, global sequencing efforts have led in the field of inborn errors of immunity, and inspired particularly by previous research on life-threatening influenza, they have revealed that known and novel inborn errors affecting type I interferon immunity underlie critical COVID-19 in up to 5% of cases. In addition, neutralizing autoantibodies against type I interferons have been identified in up to 20% of patients with critical COVID-19 who are older than 80 years and 20% of fatal cases, with a higher prevalence in men and individuals older than 70 years. Also, inborn errors impairing regulation of type I interferon responses and RNA degradation have been found as causes of multisystem inflammatory syndrome in children, a life-threatening hyperinflammatory condition complicating otherwise mild initial SARS-CoV-2 infection in children and young adults. Better understanding of these immunologic mechanisms can aid in designing treatments for severe COVID-19, multisystem inflammatory syndrome in children, long COVID, and neuro-COVID. (J Allergy Clin Immunol 2023;151:832-40.)

Automated summary

Since the start of the COVID-19 pandemic, global sequencing efforts have made significant advancements in the field of inborn errors of immunity. Research has revealed that both known and novel inborn errors affecting type I interferon immunity play a critical role in severe COVID-19 cases, occurring in up to 5% of patients. Furthermore, autoantibodies against type I interferons have been found in around 20% of critically ill COVID-19 patients over 80 years old and 20% of fatal cases, with a higher prevalence in older males. Additionally, inborn errors impairing the regulation of type I interferon responses and RNA degradation have been identified as causes of multisystem inflammatory syndrome in children, which is a life-threatening condition that occurs following mild initial SARS-CoV-2 infection in children and young adults. Understanding these immunologic mechanisms can assist in the development of treatments for severe COVID-19, multisystem inflammatory syndrome in children, long COVID, and neuro-COVID.