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

Abolhassani, Hassan; Delavari, Samaneh; Landegren, Nils; Shokri, Sima; Bastard, Paul; Du, Likun; Zuo, Fanglei; Hajebi, Reza; Abolnezhadian, Farhad; Iranparast, Sara; Modaresi, Mohammadreza; Vosughimotlagh, Ahmad; Salami, Fereshte; Aranda‐Guillén, Maribel; Cobat, Aurélie; Marcotte, Harold; Zhang, Shen-Ying; Zhang, Qian; Rezaei, Nima; Casanova, Jean‐Laurent; Kämpe, Olle; Hammarström, Lennart; Pan‐Hammarström, Qiang

doi:10.1016/j.jaci.2022.09.005

Cited by 27 publications

(128 citation statements)

References 68 publications

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“…The clinical presentation of SARS-CoV-2 infection in patients with IEI resembled that of the general population 16 , 19 inasmuch that symptoms frequently include fever, cough, headache, upper respiratory symptoms, fatigue, and dyspnea. 15 , 89 , 91 , 92 , 94 , 95 , 97 , 99 , 102 , 103 , 105 , 106 , 108 , 109 , 115 Similarly, risk factors for hospital/intensive care unit (ICU) admission and developing severe and/or fatal disease were also consistent with those determined from studies of the general population. Thus, the most severe disease was observed in older patients with IEI as well as those with pre-existing comorbidities, such as previous infection; lung, kidney, heart, or gut disease, diabetes, and obesity; or after solid organ or hematopoietic stem cell transplantation.…”

Section: Sars-cov-2 Infection Covid-19 and Ieisupporting

confidence: 65%

“…Second, the proportion of IEI patients admitted to ICU—including younger individuals—was substantially higher than the general population (10-30% vs 2-5%). 15 , 16 , 44 , 81 , 91 , 92 , 94 , 102 , 105 , 109 , 111 , 115 Third, duration of disease—likely a result of prolonged viremia and virus shedding—was longer (1-6 months vs 1-2 weeks), and the likelihood of reinfection was greater, than observed for the general population. 46 , 55 , 59 , 77 , 83 , 84 , 92 , 99 , 100 , 104 , 106 , 107 , 116 Thus, COVID-19 generally manifests clinically at a younger age, runs a more protracted course, and has a more severe outcome requiring hospitalization and/or ICU admission in many individuals with IEI compared to the epidemiology of SARS-CoV-2 infection in the general population ( Fig 2 ).…”

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 83%

“…Over the past 2 years, outcomes of SARS-CoV-2 infection have been reported for ∼1330 individuals with IEI. These studies range from reports of single cases or small numbers of patients 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 to cohort studies from Iran, 89 , 90 , 91 Turkey, 92 , 93 , 94 Brazil, 95 , 96 Israel, 97 Italy, 98 , 99 , 100 , 101 Spain, 102 the United Kingdom, 15 , 103 , 104 Mexico, 105 Denmark, 106 , 107 Poland, 108 …”

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 99%

“…Thus, the most severe disease was observed in older patients with IEI as well as those with pre-existing comorbidities, such as previous infection; lung, kidney, heart, or gut disease, diabetes, and obesity; or after solid organ or hematopoietic stem cell transplantation. 43 , 58 , 89 , 91 , 92 , 94 , 95 , 98 , 103 , 105 , 106 , 108 , 111 , 112 , 115 Other predictors of severe disease in IEI patients included leukopenia (reduced numbers of B, CD4 + T, and natural killer cells) and hypogammaglobulinemia/low IgG trough levels before infection, and increased levels of markers of systemic inflammation after infection. 43 , 46 , 58 , 66 , 103 , 109 , 111 , 114 Interestingly, and similar to the general population, ∼10% to 20% of infected IEI patients were asymptomatic, and up to another ∼30% to 50% developed only mild disease.…”

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 99%

“…First, the age of affected IEI patients was markedly younger than the general population (∼28 years vs ∼50-plus years). 16 , 44 , 79 , 81 , 84 , 89 , 91 , 93 , 94 , 95 , 100 , 102 , 103 , 104 , 108 , 109 , 110 , 115 There were also differences in age at infection for different IEI. Thus, SARS-CoV-2–infected patients with CVID, periodic fevers, or complement defects were generally older, and patients with defects in innate immune cell signaling due to pathogenic variants in IRAK4, MYD88, or IFNAR1 / IFNAR2 were generally younger, than the entire cohort of published IEI patients ( Fig 1 , A ).…”

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 99%

See 4 more Smart Citations

Impact of SARS-CoV-2 infection and COVID-19 on patients with inborn errors of immunity

Abel¹,

Al-Muhsen²,

Aiuti³

et al. 2023

Journal of Allergy and Clinical Immunology

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Section: Sars-cov-2 Infection Covid-19 and Ieisupporting

confidence: 65%

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 83%

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 99%

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 99%

Section: Sars-cov-2 Infection Covid-19 and Ieimentioning

confidence: 99%

See 3 more Smart Citations

Impact of SARS-CoV-2 infection and COVID-19 on patients with inborn errors of immunity

Abel¹,

Al-Muhsen²,

Aiuti³

et al. 2023

Journal of Allergy and Clinical Immunology

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Autoantibodies targeting type I interferons: Prevalence, mechanisms of induction, and association with viral disease susceptibility

Hale

2023

Eur J Immunol

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The type I IFN (IFN‐I) system is essential to limit severe viral disease in humans. Thus, IFN‐I deficiencies are associated with serious life‐threatening infections. Remarkably, some rare individuals with chronic autoimmune diseases develop neutralizing autoantibodies (autoAbs) against IFN‐Is thereby compromising their own innate antiviral defenses. Furthermore, the prevalence of anti‐IFN‐I autoAbs in apparently healthy individuals increases with age, such that ∼4% of those over 70 years old are affected. Here, I review the literature on factors that may predispose individuals to develop anti‐IFN‐I autoAbs, such as reduced self‐tolerance caused by defects in the genes AIRE, NFKB2, and FOXP3 (among others), or by generally impaired thymus function, including thymic involution in the elderly. In addition, I discuss the hypothesis that predisposed individuals develop anti‐IFN‐I autoAbs following “autoimmunization” with IFN‐Is generated during some acute viral infections, systemic inflammatory events, or chronic IFN‐I exposure. Finally, I highlight the enhanced susceptibility that individuals with anti‐IFN‐I autoAbs appear to have towards viral diseases such as severe COVID‐19, influenza, or herpes (e.g., varicella‐zoster virus, herpes simplex virus, cytomegalovirus), as well as adverse reactions to live‐attenuated vaccines. Understanding the mechanisms underlying development and consequences of anti‐IFN‐I autoAbs will be key to implementing effective prophylactic and therapeutic measures.

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Immunogenicity of coronavirus disease 2019 vaccines in children: A review with ChatGPT

Leung

Duque

et al. 2023

Pediatric Discovery

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SARS‐CoV‐2 causes millions of infection cases and coronavirus disease 2019 (COVID‐19)‐related deaths worldwide. In addition to acute illnesses, children and adolescents suffer from post‐infectious complications. Vaccination is a promising preventative treatment that can confer protection from these devastating outcomes. Utilizing ChatGPT, this review discusses the immunogenicity of mRNA and inactivated COVID‐19 vaccines in children and adolescents. Rapid vaccine discovery during the COVID‐19 pandemic led to the approval of the mRNA vaccines that stimulate potent antibody responses in pediatric population, and the younger age groups develop higher neutralizing and non‐neutralizing antibody responses than those who are older. Natural infection induces weaker antibody responses than vaccination. Vaccine‐induced humoral immunity decreases over time, as antibodies decline six months after the second dose. However, antibody avidity increases, which partly maintains neutralization and Fc‐effector functions that provide more durable protection. Inactivated COVID‐19 vaccines generate strong antibody responses in children and adolescents. They induce T cell responses against multiple structural protein antigens, although their neutralizing antibody responses appear weaker and wane more quickly than mRNA vaccines. Full‐dose intradermal administration and heterologous prime‐boost may improve the immunogenicity of inactivated vaccines. In children and adolescents, immune protection from the pre‐Omicron variants of concern (VOCs) is maintained. Vaccination induces less antibody neutralization against the Omicron variant, but non‐neutralizing antibodies and T cell responses persist. Hybrid immunity provides stronger immunogenicity against SARS‐CoV‐2 in the pediatric population. Future research must focus on long‐term immunity, interaction with breakthrough reinfections, cross‐reactivity against new VOCs, T cell immunogenicity and immunogenicity in young children.

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

Cited by 27 publications

References 68 publications

Impact of SARS-CoV-2 infection and COVID-19 on patients with inborn errors of immunity

Impact of SARS-CoV-2 infection and COVID-19 on patients with inborn errors of immunity

Autoantibodies targeting type I interferons: Prevalence, mechanisms of induction, and association with viral disease susceptibility

Immunogenicity of coronavirus disease 2019 vaccines in children: A review with ChatGPT

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