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Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

ABSTRACT: Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10-11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC9206114 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

Zhang Qian Q Matuozzo Daniela D Le Pen Jérémie J Lee Danyel D Moens Leen L Asano Takaki T Bohlen Jonathan J Liu Zhiyong Z Moncada-Velez Marcela M Kendir-Demirkol Yasemin Y Jing Huie H Bizien Lucy L Marchal Astrid A Abolhassani Hassan H Delafontaine Selket S Bucciol Giorgia G Bayhan Gulsum Ical GI Keles Sevgi S Kiykim Ayca A Hancerli Selda S Haerynck Filomeen F Florkin Benoit B Hatipoglu Nevin N Ozcelik Tayfun T Morelle Guillaume G Zatz Mayana M Ng Lisa F P LFP Lye David Chien DC Young Barnaby Edward BE Leo Yee-Sin YS Dalgard Clifton L CL Lifton Richard P RP Renia Laurent L Meyts Isabelle I Jouanguy Emmanuelle E Hammarström Lennart L Pan-Hammarström Qiang Q Boisson Bertrand B Bastard Paul P Su Helen C HC Boisson-Dupuis Stéphanie S Abel Laurent L Rice Charles M CM Zhang Shen-Ying SY Cobat Aurélie A Casanova Jean-Laurent JL

The Journal of experimental medicine 20220616 8

Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinicall ...[more]

PMID: 35708626

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Project description:Patients with inborn errors of immunity (IEI) in Argentina were encouraged to receive licensed Sputnik, AstraZeneca, Sinopharm, Moderna, and Pfizer vaccines, even though most of the data of humoral and cellular responses combination on available vaccines comes from trials conducted in healthy individuals. We aimed to evaluate the safety and immunogenicity of the different vaccines in IEI patients in Argentina. The study cohort included adults and pediatric IEI patients (n = 118) and age-matched healthy controls (HC) (n = 37). B cell response was evaluated by measuring IgG anti-spike/receptor binding domain (S/RBD) and anti-nucleocapsid(N) antibodies by ELISA. Neutralization antibodies were also assessed with an alpha-S protein-expressing pseudo-virus assay. The T cell response was analyzed by IFN-γ secretion on S- or N-stimulated PBMC by ELISPOT and the frequency of S-specific circulating T follicular-helper cells (TFH) was evaluated by flow cytometry.No moderate/severe vaccine-associated adverse events were observed. Anti-S/RBD titers showed significant differences in both pediatric and adult IEI patients versus the age-matched HC cohort (p < 0.05). Neutralizing antibodies were also significantly lower in the patient cohort than in age-matched HC (p < 0.01). Positive S-specific IFN-γ response was observed in 84.5% of IEI patients and 82.1% presented S-specific TFH cells. Moderna vaccines, which were mainly administered in the pediatric population, elicited a stronger humoral response in IEI patients, both in antibody titer and neutralization capacity, but the cellular immune response was similar between vaccine platforms. No difference in humoral response was observed between vaccinated patients with and without previous SARS-CoV-2 infection.In conclusion, COVID-19 vaccines showed safety in IEI patients and, although immunogenicity was lower than HC, they showed specific anti-S/RBD IgG, neutralizing antibody titers, and T cell-dependent cellular immunity with IFN-γ secreting cells. These findings may guide the recommendation for a vaccination with all the available vaccines in IEI patients to prevent COVID-19 disease.

Dataset Information

Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

Publications

Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

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