Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19.

Abolhassani H, Delavari S, Landegren N, Shokri S, Bastard P, Du L, Zuo F, Hajebi R, Abolnezhadian F, Iranparast S, Modaresi M, Vosughimotlagh A, Salami F, Aranda-Guillén M, Cobat A, Marcotte H, Zhang S, Zhang Q, Rezaei N, Casanova J, Kämpe O, Hammarström L, Pan-Hammarström Q

J Allergy Clin Immunol - (-) - [2022-09-13; online 2022-09-13]

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. 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. 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. 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%. 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.

Category: Biochemistry

Category: Health

Funder: KAW/SciLifeLab

Type: Journal article

PubMed 36113674

DOI 10.1016/j.jaci.2022.09.005

Crossref 10.1016/j.jaci.2022.09.005

pii: S0091-6749(22)01185-X
pmc: PMC9472457

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