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.
Keywords: COVID-19; Inborn errors of immunity; SARS-CoV-2; genetic diagnosis; immune response; multisystem inflammatory syndrome in children (MIS-C); primary immunodeficiency.
【저자키워드】 COVID-19, SARS-CoV-2, immune response, inborn errors of immunity, multisystem inflammatory syndrome in children (MIS-C), primary immunodeficiency., genetic diagnosis, 【초록키워드】 Treatment, coronavirus disease, antibodies, coronavirus, Mutation, Mortality, Immunity, Pneumonia, children, Genetic, whole-exome sequencing, Infection, immunodeficiency, complement, IFN signaling, COVID-19 complications, immune, COVID-19 disease, Asymptomatic, Molecular diagnosis, Pediatric patients, Patient, Complication, Mild, complications, IFN-I, plasma, Neutralizing, Inflammasome, mortality rate, disease, SARS-CoV-2-specific antibodies, patients, severe COVID-19 disease, Inflammatory, Type I IFN, autoantibody, Diagnostic Criteria, acute respiratory syndrome, individual, syndrome, help, genetic cause, MOST, hypoxemic, Inflammatory factor, Affect, tested, develop, died, reported, detectable, diagnosed, evaluated, was performed, were measured, B-cell function, children with COVID-19, Inborn error, infected with SARS-CoV-2, patients with asymptomatic, 【제목키워드】 Immunity, children, Critical,