Abstract
COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. Here we assess the difference in cellular or humoral immune responses of pediatric and adult COVID-19 patients to see if these factors contribute to the severity dichotomy. Children’s non-specific immune profile is dominated by naive lymphocytes and HLA-DRhighCX3CR1low dendritic cells; meanwhile, children show strong specific antibody and T cell responses for viral structural proteins, with their T cell responses differing from adults by having weaker CD8+TNF+ T cells responses to S peptide pool but stronger responses to N and M peptide pools. Finally, viral mRNA is more abundant in pediatric patients. Our data thus support a scenario in which SARS-CoV-2 infected children contribute to transmission yet are less susceptible to COVID-19 symptoms due to strong and differential responses to the virus.
Highlights
COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized
This is a subject of paramount importance, because it is central to the design of public policies regulating school opening during the pandemic, and because understanding the milder disease presentation in children may provide important clues for the design of prevention strategies as well as novel therapeutic pathways for the management of COVID-19
Anti-N antibody levels correlated positively with anti-N CD4+ IFNγ+ responses (Fig. 6B). These results indicate that children do generate specific humoral and effector cell responses upon infection with SARS-CoV-2, with a differential, higher cytotoxic response against proteins M and N, not associated with antibody responses to the spike protein. It is clear from our study as well as from others[25] that children do get infected by SARS-CoV-2, and possibly contribute to the community-based spread of the virus, contrary to what is suggested by studies on the low nasal Angiotensin-converting enzyme 2 (ACE2) expression in children[26]
Summary
COVID-19 manifests as a milder disease in children than adults, but the underlying mechanisms are not fully characterized. A differential immune response in children leads to a distinct infection course from adults;[9] or yet the pre-existence of neutralizing antibodies to seasonal coronaviruses could confer some crossprotection against SARS-CoV-2 induced disease. The scarcity of data prevents a clear understanding of the striking differences between the pediatric and adult outcomes after infection by SARS-CoV-2. Considerably fewer studies have focused on pediatric patients This is a subject of paramount importance, because it is central to the design of public policies regulating school opening (and all the activities associated with it) during the pandemic, and because understanding the milder disease presentation in children may provide important clues for the design of prevention strategies as well as novel therapeutic pathways for the management of COVID-19. Our findings suggest that children produce a strong, yet differential immune response when compared to adults, which associates with the mild manifestation in pediatric COVID-19
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