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
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Open Access
- 1 December 2020
- journal article
- review article
- Published by BMJ in Archives of Disease in Childhood
- Vol. 106 (5), 429-439
- https://doi.org/10.1136/archdischild-2020-320338
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.Keywords
This publication has 192 references indexed in Scilit:
- Intestinal Microbiota in Healthy U.S. Young Children and Adults—A High Throughput Microarray AnalysisPLOS ONE, 2013
- Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin–angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) studyClinica Chimica Acta; International Journal of Clinical Chemistry, 2010
- Factors that may impact on immunosenescence: an appraisalImmunity & Ageing, 2010
- Clinical Aspects of Pandemic 2009 Influenza A (H1N1) Virus InfectionThe New England Journal of Medicine, 2010
- Cyclophilin–CD147 interactions: a new target for anti-inflammatory therapeuticsClinical and Experimental Immunology, 2010
- Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and ImmunologyClinical Microbiology Reviews, 2010
- Mechanisms of immunosenescenceImmunity & Ageing, 2009
- Human Coronavirus NL63 and 229E Seroconversion in ChildrenJournal of Clinical Microbiology, 2008
- The role of melatonin in immuno‐enhancement: potential application in cancerInternational Journal of Experimental Pathology, 2006
- Inactivated SARS-CoV vaccine elicits high titers of spike protein-specific antibodies that block receptor binding and virus entryBiochemical and Biophysical Research Communications, 2004