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

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

Abolhassani, Hassan (författare): Karolinska Institutet

Delavari, Samaneh (författare): Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.

Landegren, Nils, 1986- (författare): Karolinska Institutet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.

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Shokri, Sima (författare): Iran Univ Med Sci, Hazrat e Rasool Gen Hosp, Sch Med, Dept Pediat, Tehran, Iran.

Bastard, Paul (författare): Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, Inst Natl Sante & Rech Med U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.

Du, Likun (författare): Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.

Zuo, Fanglei (författare): Karolinska Institutet

Hajebi, Reza (författare): Univ Tehran Med Sci, Dept Gen Surg, Sch Med, Sina Hosp, Tehran, Iran.

Abolnezhadian, Farhad (författare): Ahvaz Jundishapur Univ Med Sci, Dept Pediat, Abuzar Childrens Hosp, Ahvaz, Iran.

Iranparast, Sara (författare): Ahvaz Jundishapur Univ Med Sci, Fac Med Sci, Dept Immunol, Ahvaz, Iran.

Modaresi, Mohammadreza (författare): Karolinska Institutet

Vosughimotlagh, Ahmad (författare): North Khorasan Univ Med Sci, Dept Pediat, Bojnurd, Iran.

Salami, Fereshte (författare): Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.

Aranda-Guillen, Maribel (författare): Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.

Cobat, Aurelie (författare): Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, Inst Natl Sante & Rech Med U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.

Marcotte, Harold (författare): Karolinska Institutet

Zhang, Shen-Ying (författare): Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, Inst Natl Sante & Rech Med U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.

Zhang, Qian (författare): Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, Inst Natl Sante & Rech Med U1163, Paris, France.

Rezaei, Nima (författare): Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran.

Casanova, Jean-Laurent (författare): Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA.;Necker Hosp Sick Children, Necker Branch, Lab Human Genet Infect Dis, Inst Natl Sante & Rech Med U1163, Paris, France.;Univ Paris, Imagine Inst, Paris, France.;Howard Hughes Med Inst, New York, NY USA.

Kämpe, Olle (författare): Karolinska Inst, Ctr Mol Med, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.

Hammarström, Lennart (författare): Karolinska Institutet

Pan-Hammarström, Qiang (författare): Karolinska Institutet

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Karolinska Institutet Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Pediat Ctr Excellence, Childrens Med Ctr, Tehran, Iran (creator_code:org_t)

Elsevier, 2022
2022
Engelska.
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 150:5, s. 1059-1073

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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.

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

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