Children and Adults in a Household Cohort Study Have Robust Longitudinal Immune Responses Following SARS-CoV-2 Infection or Exposure

Abstract

Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.

SARS-CoV-2-specific T cell memory with common TCRαβ motifs is established in unvaccinated children who seroconvert after infection

“…Conversely, circulating tetramer-specific CD4 + and CD8 + T cells in exposed, seronegative children and adults displayed lower frequencies and a naive T cell phenotype, in accordance with their overall more diverse and unbiased TCRab repertoire observed across all T cell epitopes. Innate immune responses in a small subgroup of PCR + seronegative children may have cleared the SARS-CoV-2 infection prior to eliciting circulating adaptive immunity, as evidenced by low frequencies of predominantly naive tetramer + CD4 + and CD8 + T cells (Neeland et al, 2021a;Neeland et al, 2021b). This may also explain the observed diminished overlapping SARS-CoV-2 peptide pool stimulated CD4 + and CD8 + T cell response in SARS-CoV-2-infected children reported by others (Cohen et al, 2021;Goenka et al, 2021;Moratto et al, 2020;Pierce et al, 2020).…”

“…The lack of adaptive immunity in some children can be related to stronger early antiviral innate and mucosal immune response to SARS-CoV-2, likely contributing to rapid viral clearance and potentially explaining milder disease outcomes (Loske et al, 2022;Neeland et al, 2021aNeeland et al, , 2021bPierce et al, 2020;Toh et al, 2022;Tosif et al, 2020). Alternatively, those seronegative children may have been exposed to a lower viral load, insufficient to induce adaptive immune responses.…”

“…Children's innate immunity contributes to the rapid resolution of SARS-CoV-2 infection (Neeland et al, 2021a(Neeland et al, , 2021b. However, children can develop relatively low Spike (S)1-specific immunoglobulin G (IgG) and IgA antibody titers, mainly detected in saliva (Tosif et al, 2020), and reduced seroconversion compared with adults with mild COVID-19 (37% versus 76.2%), despite similar viral loads (Toh et al, 2022).…”

The immunopathogenesis of SARS‐CoV‐2 infection in children: diagnostics, treatment and prevention

“…Children and adults both develop protective T cell responses following infection with SARS‐CoV‐2. SARS‐CoV‐2 cross‐reactive T cells (CD4 + > CD8 + 35 ) have been reported in 20–50% of unexposed adults 36,37 . These memory T cells recognise epitopes of both SARS‐CoV‐2 and seasonal coronaviruses, potentially providing cross‐protection 38 .…”

“…SARS‐CoV‐2 cross‐reactive T cells (CD4 + > CD8 + 35 ) have been reported in 20–50% of unexposed adults. 36 , 37 These memory T cells recognise epitopes of both SARS‐CoV‐2 and seasonal coronaviruses, potentially providing cross‐protection. 38 While such studies have not yet been performed in children, this protective mechanism could similarly contribute to mild illness seen in the paediatric population.…”