{"doi":"10.1016/j.jaci.2022.09.005","title":"Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19","abstract":"BACKGROUND: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. OBJECTIVE: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. METHODS: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. RESULTS: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. CONCLUSIONS: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.","journal":"Journal of Allergy and Clinical Immunology","year":2022,"id":241319,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":870093,"name":"Samaneh Delavari","orcid":"0000-0003-0122-0657","position":1,"is_corresponding":false},{"id":853499,"name":"Nils Landegren","orcid":"0000-0002-6163-9540","position":2,"is_corresponding":false},{"id":870094,"name":"Sima Shokri","orcid":"0000-0002-2176-3934","position":3,"is_corresponding":false},{"id":104138,"name":"Paul Bastard","orcid":"0000-0002-5926-8437","position":4,"is_corresponding":false},{"id":852564,"name":"Likun Du","orcid":"0000-0002-8448-2187","position":5,"is_corresponding":false},{"id":853502,"name":"Fanglei Zuo","orcid":"0000-0002-4545-1265","position":6,"is_corresponding":false},{"id":870095,"name":"Reza Hajebi","orcid":"0000-0002-1021-3363","position":7,"is_corresponding":false},{"id":870096,"name":"Farhad Abolnezhadian","orcid":"0000-0003-1197-7207","position":8,"is_corresponding":false},{"id":870097,"name":"Sara Iranparast","orcid":"0000-0002-5134-487X","position":9,"is_corresponding":false},{"id":853500,"name":"Mohammadreza Modaresi","orcid":"0000-0002-2132-9126","position":10,"is_corresponding":false},{"id":870667,"name":"Ahmad Vosughimotlagh","orcid":null,"position":11,"is_corresponding":false},{"id":870668,"name":"Fereshte Salami","orcid":null,"position":12,"is_corresponding":false},{"id":853501,"name":"Maribel Aranda‐Guillén","orcid":"0000-0003-0050-704X","position":13,"is_corresponding":false},{"id":57371,"name":"Aurélie Cobat","orcid":"0000-0001-7209-6257","position":14,"is_corresponding":false},{"id":853503,"name":"Harold Marcotte","orcid":"0000-0002-7168-349X","position":15,"is_corresponding":false},{"id":57374,"name":"Shen-Ying Zhang","orcid":"0000-0002-9449-3672","position":16,"is_corresponding":false},{"id":104140,"name":"Qian Zhang","orcid":"0000-0002-9040-3289","position":17,"is_corresponding":false},{"id":6925,"name":"Nima Rezaei","orcid":"0000-0002-3836-1827","position":18,"is_corresponding":false},{"id":57373,"name":"Jean-Laurent Casanova","orcid":"0000-0002-7782-4169","position":19,"is_corresponding":false},{"id":355654,"name":"Olle Kämpe","orcid":"0000-0001-6091-9914","position":20,"is_corresponding":false},{"id":281914,"name":"Lennart Hammarström","orcid":"0000-0002-8635-9609","position":21,"is_corresponding":false},{"id":14420,"name":"Qiang Pan‐Hammarström","orcid":"0000-0003-1990-8804","position":22,"is_corresponding":false},{"id":48203,"name":"Hassan Abolhassani","orcid":"0000-0002-4838-0407","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"36113674","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}