Pathophysiology of COVID-19: Why Children Fare Better than Adults?

Indian J Pediatr. 2020 Jul;87(7):537-546. doi: 10.1007/s12098-020-03322-y. Epub 2020 May 14.


The world is facing Coronavirus Disease-2019 (COVID-19) pandemic, which is causing a large number of deaths and burden on intensive care facilities. It is caused by Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) originating in Wuhan, China. It has been seen that fewer children contract COVID-19 and among infected, children have less severe disease. Insights in pathophysiological mechanisms of less severity in children could be important for devising therapeutics for high-risk adults and elderly. Early closing of schools and day-care centers led to less frequent exposure and hence, lower infection rate in children. The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation. Severe COVID-19 disease is associated with high and persistent viral loads in adults. Children have strong innate immune response due to trained immunity (secondary to live-vaccines and frequent viral infections), leading to probably early control of infection at the site of entry. Adult patients show suppressed adaptive immunity and dysfunctional over-active innate immune response in severe infections, which is not seen in children. These could be related to immune-senescence in elderly. Excellent regeneration capacity of pediatric alveolar epithelium may be contributing to early recovery from COVID-19. Children, less frequently, have risk factors such as co-morbidities, smoking, and obesity. But young infants and children with pre-existing illnesses could be high risk groups and need careful monitoring. Studies describing immune-pathogenesis in COVID-19 are lacking in children and need urgent attention.

Keywords: ACE-2; Adaptive immunity; Innate immunity; Pathogenesis; SARS-CoV2.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity
  • Adult
  • Age Factors*
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / pathogenicity*
  • COVID-19
  • Child
  • China / epidemiology
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / immunology
  • Coronavirus Infections / physiopathology*
  • Coronavirus Infections / transmission
  • Disease Susceptibility
  • Humans
  • Influenza, Human / epidemiology
  • Influenza, Human / immunology
  • Influenza, Human / physiopathology
  • Influenza, Human / transmission
  • Middle East Respiratory Syndrome Coronavirus / pathogenicity
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / epidemiology
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / physiopathology*
  • Pneumonia, Viral / transmission
  • Risk Factors
  • SARS Virus / pathogenicity
  • SARS-CoV-2
  • United States / epidemiology


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2