key: cord-0911637-6vwxm2t8
authors: Ruggiero, Antonio; Attinà, Giorgio; Chiaretti, Antonio
title: Additional hypotheses about why COVID‐19 is milder in children than adults
date: 2020-05-17
journal: Acta Paediatr
DOI: 10.1111/apa.15328
sha: 42cc614152febe8c96fac43461e2128fc5732713
doc_id: 911637
cord_uid: 6vwxm2t8

We read with great interest the editorial by Brodin discussing why COVID-19 appears to be so mild in children (1). In particular, the author discussed the potential theories that could explain why children have a lower incidence and milder clinical manifestations than adults. However, we feel it is important to present some other additional hypotheses in order to address all the potential theories.

We read with great interest the editorial by Brodin discussing why COVID-19 appears to be so mild in children. 1 In particular, the author discussed the potential theories that could explain why children have a lower incidence and milder clinical manifestations than adults. However, we feel it is important to present some other additional hypotheses in order to address all the potential theories.

In the last SARS-CoV epidemic in 2002, milder clinical manifestations were observed in children and it was hypothesised that children's vaccines could have induced cross reactivity against SARS-CoV. 2 Unfortunately, this hypothesis was not confirmed and other factors, namely the inability to mount a hormone response or upregulation of some ant-inflammatory cytokines, were presented to explain the phenomenon.

However, we probably need to consider another theory. Ageing is associated with a progressive decline in the normal functioning of the immune system, which leads to weaker immune responses and impairs a person's ability to respond to new stimulants. This process involves the natural involution of the thymus, starting during or soon after the first year of birth. It then shows an accelerated decline after puberty, and the thymic microenvironment cells continue to reduce by 3% to 5% a year until approximately 30-40 years of age before slowing down to less than 1% per year. 3 After the fourth and fifth decade of life, the involution of the thymus leads to a significant decline in naїve T cell output. This affects the composition of the peripheral CD4 and CD8 T-cell pool and has a negative influence on the adaptive immunity that is considered to be the leading cause of morbidity and mortality in the elderly. 4 In our opinion, the functional and phenotypic features of children's immune systems should be included when explaining their age-dependent susceptibility to COVID-19 and the severity of any disease.

https://orcid.org/0000-0002-6052-3511

Why is COVID-19 so mild in children? Acta Paediatr

Children's vaccines do not induce cross reactivity against SARS-CoV

Involution of the mammalian thymus, one of the leading regulators of aging

Thymus and aging: morphological, radiological, and functional overview

Dysregulation of immune response in patients with COVID-19 in Wuhan, China