Background Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the mechanism underlying life-threatening COVID-19 is instrumental for disease prevention and treatment in individuals with a high risk. Objectives We aimed to identify the genetic cause for critical COVID-19 pneumonia in a patient with a preexisting inborn error of immunity (IEI). Methods Serum levels of specific antibodies against the virus and autoantibodies against type I interferons (IFNs) were measured. Whole exome sequencing was performed, and the impacts of candidate gene variants were investigated. We also evaluated 247 ataxia-telangiectasia (A-T) patients in the Iranian IEI registry. Results We report a 7-year-old Iranian boy with a preexisting hyper IgM syndrome who developed critical COVID-19 pneumonia. IgM only specific COVID-19 immune response was detected but no autoantibodies against type I IFN were observed. A homozygous deleterious mutation in the ATM gene was identified, which together with his antibody deficiency, radiosensitivity, and neurological signs, established a diagnosis of A-T. Among the 247 A-T patients evaluated, 36 had SARS-CoV-2 infection, but all had mild symptoms or were asymptomatic except the index patient. A hemizygous deleterious mutation in the TLR7 gene was subsequently identified in the patient. Conclusions We report a unique IEI patient with combined ATM and TLR7 deficiencies. The two genetic defects underlie A-T and critical COVID-19 in this patient, respectively. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-021-01151-y.
【저자키워드】 COVID-19, TLR7, Primary Immunodeficiency, Antibody deficiency, critical COVID-19, inborn errors of immunity, ataxia-telangiectasia, ATM, 【초록키워드】 Treatment, coronavirus disease, IgM, Coronavirus disease 2019, COVID-19 pneumonia, immune response, Mutation, Immunity, Pneumonia, antibody, SARS-COV-2 infection, Sequencing, variant, interferons, TLR7, Diagnosis, virus, type I interferon, clinical manifestations, Asymptomatic, autoantibodies, Impact, Patient, understanding, type I interferons, disease, Critical, mechanism, IFNs, mild symptoms, COVID-19 immune response, specific antibodies, Deleterious, candidate gene, Type I IFN, autoantibody, high risk, Ataxia, deficiency, Mild symptom, supplementary material, Exome, deficiencies, genetic defects, serum levels, individual, syndrome, life-threatening, neurological signs, genetic cause, homozygous, TLR7 gene, genetic defect, telangiectasia, radiosensitivity, objective, Result, identify, the patient, investigated, specific antibody, evaluated, was performed, unique, conditions, exhibit, were measured, underlie, patients evaluated,