ABSTRACT
SARS-CoV-2 is still a major burden for global health despite effective vaccines. With the reduction of social distancing measures, infection rates are increasing in children, while data on the pediatric immune response to SARS-CoV-2 infection is still lacking. Although the typical disease course in children has been mild, emerging variants may present new challenges in this age group. Peripheral blood mononuclear cells (PBMC) from 51 convalescent children, 24 seronegative siblings from early 2020, and 51 unexposed controls were stimulated with SARS-CoV-2-derived peptide MegaPools from the ancestral and beta variants. Flow cytometric determination of activation-induced markers and secreted cytokines were used to quantify the CD4+ T cell response. The average time after infection was over 80 days. CD4+ T cell responses were detected in 61% of convalescent children and were markedly reduced in preschool children. Cross-reactive T cells for the SARS-CoV-2 beta variant were identified in 45% of cases after infection with an ancestral SARS-CoV-2 variant. The CD4+ T cell response was accompanied most predominantly by IFN- γ and Granzyme B secretion. An antiviral CD4+ T cell response was present in children after ancestral SARS-CoV-2 infection, which was reduced in the youngest age group. We detected significant cross-reactivity of CD4+ T cell responses to the more recently evolved immune-escaping beta variant. Our findings have epidemiologic relevance for children regarding novel viral variants of concern and vaccination efforts.
Subject(s)
COVID-19ABSTRACT
Background: Investigating the role of children in the COVID-19 pandemic is pivotal to prevent the virus spreading. In most cases, children infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) develop non-specific symptoms or are asymptomatic. Therefore, the infection rate among this age group remains unclear. Seroprevalence studies, including clinical questionnaires, may contribute to our understanding of the time course and clinical manifestations of SARS-CoV-2 infections.Methods: SARS-CoV-2-KIDS is a longitudinal, hospital-based, multicentre study in Germany on the seroprevalence of anti-SARS-CoV-2 immunoglobulin G, as determined by an Enzyme-Linked Immunosorbent Assay in children (aged ≤17 years). A study-specific questionnaire provided additional information on clinical aspects.Findings: This analysis included 10,358 participants recruited from June 2020 to May 2021. The estimated anti-SARS-CoV-2 seroprevalence increased from 2·0% (95% confidence interval (95% CI) 1·6, 2·5) to 10·8% (95% CI 8·7, 12·9) in March 2021, without major change afterwards and was higher in children with migrant background (on average 6·6% vs. 2·8%). In the pandemic early stages, children under three years were 3·5 (95% CI 2·2, 5·6) times more likely to be seropositive than older children, with the levels equalising in later observations. History of self-reported respiratory tract infections or pneumonia was associated with seropositivity (OR 1·8 (95% CI 1·4, 2·3); 2·7 (95% CI 1·7, 4·1)).Interpretation: The majority of children in Germany do not have detectable SARS-CoV-2 IgG. To some extent, this may reflect the effect of differing containment measures implemented in the federal states. Detection levels might have been greater in certain age groups or migrant background. Lifting containment measurements is likely to cause a general increase in respiratory tract infections, which already pose a challenge to paediatric medical care during regular winter seasons. This challenge might become critical with additional infections caused by SARS-CoV-2.Funding: Funding Information: German Federal Ministry of Education and Research.Declaration of Interests: Authors have no conflicts of interest to declare.Ethics Approval Statement: Ethics committees of each study centre independently approved the study protocol. All parents/guardians gave written informed consent and children assented to the participation when appropriate for their age.
Subject(s)
COVID-19 , Pneumonia , Severe Acute Respiratory SyndromeABSTRACT
Background: In response to the current pandemic, closure of school and day care facilities has been broadly implemented, markedly affecting children worldwide. The infectibility and infectiousness of children by SARS-CoV-2 require further study.Methods: The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) study screened 6113 children <18 years for SARS-CoV-2 infection by nasopharyngeal swab-PCR in a low-incidence setting. A total of 4657 participants underwent antibody testing. Positive PCR and/or antibody tests were followed by PCR and serological testing of household contacts.Findings: One child tested positive by PCR for SARS-CoV-2. Seroprevalence in children increased with age (OR: 1·11 per year, P=0·009). In children with reported exposure to SARS-CoV-2, probability of seroconversion was also higher in older children (children 6 - <12 OR: 1·1, and 12 - <18 years OR: 3·2 vs. children <6 years). Follow-up of household contacts showed incomplete seroconversion in most families. Seroconversion rates were higher in families, where the index patient was an adult than in families with paediatric index cases (OR: 1·79, P=0·047).Interpretation: Seroprevalence in children increases with age, also in children with known exposure to SARS-CoV-2, suggesting a lower infectibility of younger children. Infectiousness of children may be lower than adults, as lower seroconversion rates characterised families of paediatric index cases compared to families of adult index cases. The spread of SARS-CoV-2 may be limited in small communities (families, schools, kindergartens) when young children are part of the infection process.Trial Registration: clinicaltrials.gov (NCT04534608).Funding: This study was funded by private contributions and the City of Hamburg.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: The study was approved by the local ethical committee of Hamburg (reference number: PV7336).