tetano
Editor, Senior Moderator
Clin Exp Immunol
. 2024 Jul 19:uxae062.
doi: 10.1093/cei/uxae062. Online ahead of print. Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children
Halima Kholaiq[SUP] 1 [/SUP], Yousra Abdelmoumen[SUP] 1 [/SUP], Abderrahmane Moundir[SUP] 1 [/SUP], Assiya El Kettani[SUP] 1 2 3 [/SUP], Fatima Ailal[SUP] 1 4 [/SUP], Ibtihal Benhsaien[SUP] 1 4 [/SUP], Fatima Adnane[SUP] 1 4 [/SUP], Asmaa Drissi Bourhanbour[SUP] 1 5 [/SUP], Naima Amenzoui[SUP] 1 4 [/SUP], Jalila El Bakkouri[SUP] 1 5 6 [/SUP], Ahmed Aziz Bousfiha[SUP] 1 4 [/SUP]
Affiliations
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections.
Keywords: COVID-19 pneumonia; Inborn errors of immunity; Interferon type I; Multisystem inflammatory syndrome in children (MIS-C); SARS-CoV-2; Viral infections.
. 2024 Jul 19:uxae062.
doi: 10.1093/cei/uxae062. Online ahead of print. Human Genetic and Immunological Determinants of SARS-CoV-2 Infection and Multisystem Inflammatory Syndrome in Children
Halima Kholaiq[SUP] 1 [/SUP], Yousra Abdelmoumen[SUP] 1 [/SUP], Abderrahmane Moundir[SUP] 1 [/SUP], Assiya El Kettani[SUP] 1 2 3 [/SUP], Fatima Ailal[SUP] 1 4 [/SUP], Ibtihal Benhsaien[SUP] 1 4 [/SUP], Fatima Adnane[SUP] 1 4 [/SUP], Asmaa Drissi Bourhanbour[SUP] 1 5 [/SUP], Naima Amenzoui[SUP] 1 4 [/SUP], Jalila El Bakkouri[SUP] 1 5 6 [/SUP], Ahmed Aziz Bousfiha[SUP] 1 4 [/SUP]
Affiliations
- PMID: 39028583
- DOI: 10.1093/cei/uxae062
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces pneumonia and acute respiratory failure in Coronavirus Disease 2019 (COVID-19) patients with inborn errors of immunity to type I interferon (IFN-I). The impact of SARS-CoV-2 infection varies widely, ranging from mild respiratory symptoms to life-threatening illness and organ failure, with a higher incidence in men than in women. Approximately 3 to 5% of critical COVID-19 patients under 60 and a smaller percentage of elderly patients exhibit genetic defects in IFN-I production, including X-chromosome-linked TLR7 and autosomal TLR3 deficiencies. Around 15 to 20% of cases over 70 years old, and a smaller percentage of younger patients, present with preexisting autoantibodies neutralizing type I interferons. Additionally, innate errors affecting the control of the response to type I interferon have been associated with pediatric multisystem inflammatory syndrome (MIS-C). Several studies have described rare errors of immunity, such as XIAP deficiency, CYBB, SOCS1, OAS1/2, and RNASEL, as underlying factors in MIS-C susceptibility. However, further investigations in expanded patient cohorts are needed to validate these findings and pave the way for new genetic approaches to MIS-C. This review aims to present recent evidence from the scientific literature on genetic and immunological abnormalities predisposing individuals to critical SARS-CoV-2 infection through IFN-I. We will also discuss multisystem inflammatory syndrome in children (MIS-C). Understanding the immunological mechanisms and pathogenesis of severe COVID-19 may inform personalized patient care and population protection strategies against future serious viral infections.
Keywords: COVID-19 pneumonia; Inborn errors of immunity; Interferon type I; Multisystem inflammatory syndrome in children (MIS-C); SARS-CoV-2; Viral infections.