Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections

“Abstract: In contrast to other respiratory viruses, children have less severe symptoms when infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we discuss proposed hypotheses for the age-related difference in severity of coronavirus disease 2019 (COVID-19).

Factors proposed to explain the difference in severity of COVID-19 in children and adults include those that put adults at higher risk and those that protect children. The former include:

(1) age-related increase in endothelial damage and changes in clotting function;

(2) higher density, increased affinity and different distribution of angiotensin converting enzyme 2 receptors and transmembrane serine protease 2;

(3) pre-existing coronavirus antibodies (including antibody-dependent enhancement) and T cells;

(4) immunosenescence and inflammaging, including the effects of chronic cytomegalovirus infection;

(5) a higher prevalence of comorbidities associated with severe COVID-19 and

(6) lower levels of vitamin D.

Factors that might protect children include:

(1) differences in innate and adaptive immunity;

(2) more frequent recurrent and concurrent infections;

(3) pre-existing immunity to coronaviruses;

(4) differences in microbiota;

(5) higher levels of melatonin;

(6) protective off-target effects of live vaccines and

(7) lower intensity of exposure to SARS-CoV-2.”