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Journal Articles Infectious Diseases Research Year : 2022

Why are children and many adults not affected by COVID-19? Role of the host immune response

Hélène Banoun
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Children are less susceptible to COVID-19 than adults: they often have asymptomatic and very rarely severe forms. This protection is valid for all variants of the virus. The aim here is to compare the immune response of children with that of adults, asymptomatic adults or those with mild disease with those who develop severe Covid. Several protective factors for children have been mentioned but some of them do not seem to be involved. Indeed, there is no clear difference in the quantity of virus receptors (angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2)) present according to age that could explain a lesser entry of the virus into the cells of the nose, oropharynx and lungs of children. In fact, children and adults generally have similar viral loads and respiratory tract excretions. Most adults, like children, have antibodies (and T cells) that cross-react with human coronavirus (HCoVs) and respiratory syndrome coronavirus 2 (SARS-CoV-2), but this humoral reactivity does not correlate with disease severity in adults; the difference appears to be more qualitative (IgM and anti-S in children and IgG and IgA and anti-N in adults) than quantitative, and mildly affected adults have some of the characteristics of the cross-reactivities of children. At the cellular level, the difference between children and adults lies more in the naivety of the T cells involved. The amount of salivary and mucosal IgA is negatively correlated with age and positively correlated with the absence of Covid infection: these IgAs are different and more effective than serum IgA. Severe COVID-19 is characterized by hyperinflammation following invasion of the lower respiratory tract when the virus has not been cleared from the upper respiratory tract by innate immunity. Age is associated with an alteration of the immune system, often with a chronic hyperinflammatory state: deficient innate immunity combined with age-related dysregulation of adaptive immunity could cause severe COVID-19. The innate cellular response in the upper and lower airways is more effective in asymptomatic children and adults: the interferon response is earlier and involves immune rather than epithelial cells, the latter being associated with hyperinflammation. This early response is critical given the ability of SARS-CoV-2 to suppress interferon 1 (IFN-1) responses. Regulatory Treg cells (which prevent the inflammatory response from spiraling out of control) are prevalent in the respiratory tissues of children. The response of myeloid cells (neutrophils and macrophages/monocytes), which are also responsible for hyperinflammation, is also qualitatively different in mildly affected children and adults compared to severe Covid: there is enrichment of classical monocytes and dysfunctional neutrophils in severe cases. It would be useful to explore why the response of children to SARS-CoV-2 is the opposite of that to influenza virus (which causes classical monocyte influx and overproduction of inflammatory cytokines). Oral dysbiosis is associated with severe COVID-19 and the diversity of the oropharyngeal microbiota is inversely correlated with age. Mycoplasma co-infections amplify viral replication and are associated with severe Covid; children may have more protective anti-mycoplasma IgG because they are more frequently exposed to community infections. The role of hyperinflammation in severe COVID-19 justifies the use of immunomodulatory drugs: hydroxychloroquine, ivermectin, anti-histamines, corticosteroids. Probiotics have been used to restore the gut microbiota that interacts with the lung microbiota. Reduction of the permeability of the intestinal barrier has been proposed. Treatment of immune aging with a prostaglandin inhibitor works well in aged mice by restoring dendritic cell migration. Stimulation of innate immunity by a pathogen recognition motif receptor agonist works in mice.
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hal-03754848 , version 1 (20-08-2022)



Hélène Banoun. Why are children and many adults not affected by COVID-19? Role of the host immune response. Infectious Diseases Research, 2022, 3 (3), pp.18. ⟨10.53388/IDR20220825018⟩. ⟨hal-03754848⟩
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