13 possible reasons why COVID-19 is less severe in children – Dec 1, 2020

Review Arch Dis Child. 2020 Dec 1; doi: 10.1136/archdischild-2020-320338
Petra Zimmermann 1 2 3, Nigel Curtis 3 4 5


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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.

Lower levels of vitamin D (clipped frm PDF)

Vitamin D has anti-inflammatory and anti-oxidative properties,114 and vitamin D deficiency has been associated with an increased risk for the development of respiratory tract infections.115 Mechanisms by which vitamin D might protect against respiratory viruses include increasing viral killing, reducing synthesis of pro-inflammatory cytokines and protecting the integrity of tight junctions thereby preventing infiltration of immune cells into lungs.116
The overlap between risk factors for severe COVID-19 and vitamin D deficiency, including obesity,117 chronic kidney disease118 and black or Asian origin,119 suggests that vitamin D supplementation may play a role in prophylaxis or treatment of COVID-19.114 In many countries, vitamin D is routinely supplemented in infants younger than 1 year of age and in some countries even up to the age of 3 years. Furthermore, vitamin D levels are lower in older age groups, especially in men, in whom supplementation is less frequent.120 Several studies report a negative correlation between estimates of average vitamin D levels in the population and the incidence and mortality from COVID-19.121-123 One study found lower vitamin D levels in SARS-CoV-2-positive individuals compared with SARS-CoV- 2-negative individuals, even after stratifying for age over 70 years.124 Another study found lower vitamin D levels in patients with COVID-19 compared with sex-matched, age-matched and season-matched controls.125 Furthermore, the level of vitamin D was negatively correlated with the severity of radiological findings. Two other studies also found a correlation between low vitamin D levels and COVID-19 severity and mortality.126 127

In vitro studies show that calcitriol, the active form of vitamin D, has antiviral activity against SARS-CoV-2.128 A further important finding from a study in rats shows that vitamin D alleviates lipopolysaccharide– reduced acute lung injury via the renin-angiotensin system (RAS),129 which is important in the pathogenesis of COVID-19, in which the degree of overactivation of the RAS is associated with poorer prognosis. Low vitamin D levels lead to higher RAS activity and higher angiotensin II concentrations.130

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