Children and SARS-CoV-2

Bogunovic, Dusan; Mérad, Miriam

doi:10.1016/j.chom.2021.06.015

Cited by 18 publications

(20 citation statements)

References 16 publications

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“…Although the majority of infected individuals recover, it remains important to identify factors that put patients at greater risk for severe disease. Age is the major epidemiological risk factor of death from pneumonia, the risk doubling every five years of age from childhood onward ( 3 – 5 ). Patients with inborn errors (IE) of immunity affecting the production of, or response to type I IFNs, or both, are prone to critical COVID-19 pneumonia ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

et al. 2023

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Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

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Section: Introductionmentioning

confidence: 99%

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

et al. 2023

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“…Risk factors predisposing to severe COVID-19 are male sex, the presence of comorbidities and an older age, whereas children commonly develop a mild disease after SARS-CoV-2 infection ( 1 ). The mechanisms that protect the younger from severe COVID-19 disease are yet to be defined; reasons may be a low expression of the ACE2 receptor, trained immunity, a higher capacity to regenerate cells after viral damage but also a strong and effective innate and/or adaptive immune response to SARS-CoV-2 ( 1 – 3 ). SARS-CoV-2 replication starts in nasopharyngeal mucosal cells and recognition of viral molecular patterns leads to a rapid activation of antiviral and inflammatory responses ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison by Age of the Local Interferon Response to SARS-CoV-2 Suggests a Role for IFN-ε and -ω

et al. 2022

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Children generally develop a mild disease after SARS-CoV-2 infection whereas older adults are at risk of developing severe COVID-19. Recent transcriptomic analysis showed pre-activated innate immunity in children, resulting in a more effective anti-SARS-CoV-2 response upon infection. To further characterize age-related differences, we studied type I and III interferon (IFN) response in SARS-CoV-2 infected and non-infected individuals of different ages. Specifically, levels of expression of type I (IFN-α, -β, -ε and -ω), type III (IFN-λ1, -λ2 and -λ3) IFNs and of the IFN-stimulated genes, ISG15 and ISG56 were quantified in nasopharyngeal cells from diagnostic swabs. Basal transcription of type I/III IFN genes was highest among children and decreased with age. Among SARS-CoV-2-infected individuals, only IFN-ε and -ω levels were significantly higher in children and young adults whereas ISGs were overexpressed in infected adults. The occurrence of symptoms in children and the need for hospitalization in adults were associated to higher transcription of several IFN genes. Starting from a pre-activated transcription level, the expression of type I and III IFNs was not highly up-regulated in children upon SARS-CoV-2 infection; young adults activated IFNs’ transcription at intermediate levels whereas older adults were characterized by higher ISGs and lower IFN-ε and -ω relative expression levels. Overall, our findings contribute to recognize components of a protective IFN response as a function of age, in the context of SARS-CoV-2 infection.

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“…Such methods could also improve our understanding of the mechanisms resulting in long-term sequelae of severe COVID-19. Multisystem inflammatory syndrome in children/adolescence Multisystem inflammatory syndrome in children/adolescence (MIS-C/A) is a rare complication seen in children and adolescents who present with a hyper inflammatory syndrome at 4-6 weeks after SARS-CoV-2 infection (see Bogunovic and Merad, 2021 in this issue for a complete discussion). Early biomarkers that predict MIS-C/A are needed to protect children from this rare yet devastating outcome of SARS-CoV-2 infection.…”

Section: Covid-19 Clinical Presentations and Syndromes Related To Inflammationmentioning

confidence: 99%

An aberrant inflammatory response in severe COVID-19

Mérad

Subramanian

Wang

2021

Cell Host & Microbe

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Children and SARS-CoV-2

Cited by 18 publications

References 16 publications

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Comparison by Age of the Local Interferon Response to SARS-CoV-2 Suggests a Role for IFN-ε and -ω

An aberrant inflammatory response in severe COVID-19

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