Local and systemic responses to SARS-CoV-2 infection in children and adults

Abstract

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Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge

“…In this study, the lower level of CRP and IL-6 was observed in the younger children, which may indicate a milder overall inflammatory response and a good prognosis in this population ( Liu et al., 2020 ). The younger children in the current study reported a higher lymphocyte count than their counterparts, which might be due to different physiological status ( Yoshida et al., 2021 ) and different disease conditions between them ( Viau & Zouali, 2005 ; Bieberich et al., 2021 )…”

“…As for the mild disease status observed in the younger children, a recent study reported that the expression of ACE-2 receptor is lower in the upper and lower airways of children than in the nasal epithelium of healthy adults, resulting in a lower risk of SARS-Cov-2 infection in this population ( Yoshida et al., 2021 ). Furthermore, the milder condition in the younger patient cohort may be closely related to the potent innate immunity of the children.…”

“…Previous studies ( Vono et al., 2021 ; Winkley et al., 2021 ; Pierce et al., 2021 ), indicated that, compared with adults, younger children had a more robust mucosal response to prevent immune escape of the virus and generate an immediate barrier to viral infection. What is more, a recent study documented that the activated interferons in the respiratory mucosa of the children may protect them against SARS-CoV-2 infection ( Yoshida et al., 2021 ), in which children had a significant increase of naive lymphocytes and decrease of NK cells in the systemic response, quite different from adults who had more cytotoxic T-cells (CTL) that were interferon-responsive cells. The presence of fewer interferon-responsive cells in the respiratory tract of the children may also account for a mild inflammatory response in the COVID-19 condition of the children.…”

Distinct upper airway epithelium interferon-stimulated and profibrotic gene expression between adult and infant rhesus macaques infected with SARS-CoV-2

“…Considering trachea RNA-seq data was collected at day 14 post-inoculation in our study, when viral loads were not detectable anymore, it is possible that levels of some ISGs are upregulated in infants at baseline compared to adults. Indeed, this has been demonstrated in multiple pediatric cohorts where ISGs (40) and cytokines and chemokine genes (41) were increased in SARS-CoV-2-uninfected children compared to adults. Upon SARS-CoV-2 infection, children’s IFN-α responses were greater in multiple immune cell subsets including NK CD56 low , NKT cells, neutrophils, CXCL10+ monocytes and some CD8+ T cell subsets (40).…”

“…Indeed, this has been demonstrated in multiple pediatric cohorts where ISGs (40) and cytokines and chemokine genes (41) were increased in SARS-CoV-2-uninfected children compared to adults. Upon SARS-CoV-2 infection, children’s IFN-α responses were greater in multiple immune cell subsets including NK CD56 low , NKT cells, neutrophils, CXCL10+ monocytes and some CD8+ T cell subsets (40). These data suggest the IFN response in children is pre-activated in epithelial cells of the upper airways and stronger in immune cell subsets compared to adults.…”