TY - JOUR T1 - 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 JF - Archives of Disease in Childhood JO - Arch Dis Child DO - 10.1136/archdischild-2020-320338 SP - archdischild-2020-320338 AU - Petra Zimmermann AU - Nigel Curtis Y1 - 2020/11/30 UR - http://adc.bmj.com/content/early/2020/11/30/archdischild-2020-320338.abstract N2 - 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. ER -