Genetic and immunologic evaluation of children with inborn errors of immunity and severe or critical COVID-19 - 03/11/22
, Qiang Pan-Hammarström, MD, PhD a, ⁎
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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.
Le texte complet de cet article est disponible en PDF.Key words : Inborn errors of immunity, primary immunodeficiency, SARS-CoV-2, COVID-19, multisystem inflammatory syndrome in children (MIS-C), genetic diagnosis, immune response
Abbreviations used : ACMG, CID, COVID-19, HRCT, ICU, IEI, IFN-I, IUIS, KD, MIS-C, NF-κB, PAD, RBD, SARS-CoV-2, TLR, WES
Plan
| This project received funding from the European Union’s Horizon 2020 research and innovation program (ATAC, 101003650), the Swedish Research Council, the Swedish Cancer Society, Jeffrey Modell Foundation and the Knut and Alice Wallenberg Foundation (KAW). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St Giles Foundation, the National Institutes of Health (NIH) (R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Fisher Center for Alzheimer's Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), ANR grants (ANR-14-CE14-0008-01, ANR-18-CE15-0020-02, ANR-20-CE93-003, ANR-20-CO11-000,1 and ANR-21-COVR-0039), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCovid project (ANR-20-COVI-0003), ANRS Nord-Sud (ANRS-COV05), the European Union’s Horizon 2020 research and innovation program under grant 824110 (EASI-Genomics), the Square Foundation, Grandir-Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Fondation du Souffle, Institut National de la Santé et de la Recherche Médicale (Inserm), REACTing-INSERM, and the University of Paris. P.B. was supported by the French Foundation for Medical Research (FRM, EA20170638020). P.B. was supported by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 150 - N° 5
P. 1059-1073 - novembre 2022 Retour au numéro
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