{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:34:24Z","timestamp":1784043264100,"version":"3.55.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T00:00:00Z","timestamp":1721347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>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\u20135% 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\u201320% 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.<\/jats:p>","DOI":"10.1093\/cei\/uxae062","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T22:37:29Z","timestamp":1721255849000},"source":"Crossref","is-referenced-by-count":3,"title":["Human genetic and immunological determinants of SARS-CoV-2 infection and multisystem inflammatory syndrome in children"],"prefix":"10.1093","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4373-7579","authenticated-orcid":false,"given":"Halima","family":"Kholaiq","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Immunology, Inflammation and Allergies (LICIA), Faculty of Medicine and Pharmacy, Hassan II University , Casablanca 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,","place":["Morocco"]},{"name":"Laboratory of Bacteriology, Virology and Hospital Hygiene, Ibn Rochd University Hospital , Casablanca ,","place":["Morocco"]},{"name":"Laboratory of Bacteriology and Virology, Faculty of Medicine and Pharmacy, Hassan II University , Casablanca ,","place":["Morocco"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Ailal","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Inflammation and Allergies (LICIA), Faculty of Medicine and Pharmacy, Hassan II University , Casablanca ,","place":["Morocco"]},{"name":"Clinical Immunology and Infectious Pediatrics Department, Abderrahim Harouchi Hospital, Ibn Rochd University Hospital , Casablanca ,","place":["Morocco"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibtihal","family":"Benhsaien","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Immunology, Inflammation and Allergies (LICIA), Faculty of Medicine and 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