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

Abstract

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.

COVID-19 in the Pediatric Population—Review and Current Evidence

“…Additional suggested explanations are alterations in T cell populations in adults due to continuous antigen stimulation and thymic involution, varied levels of ACE-2 expression in children, and the simultaneous presence of other viruses in the respiratory mucosa of children, competing with SARS-CoV-2 [10]. Furthermore, children have fewer comorbidities and a stronger pulmonary regenerative potential than adults [11].…”

Geriatric Population During the COVID-19 Pandemic: Problems, Considerations, Exigencies, and Beyond

“…In addition to compromised organ function and immunity in the elderly, pathophysiological susceptibility also increases their vulnerability, attack rate, and infectivity by SARS-CoV-2 (31). The pneumonia severity index (PSI) score is higher in the elderly than that in the young and middle-aged individuals (15).…”

Afebrile Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection have a Longer Viral Positivity Duration: A Retrospective Analysis of 125 Patients

“…Given the high plasticity of adaptive responses in children, particularly in their B lymphocyte compartment, could more e ciently clear the virus [40]. What's more, angiotensin converting enzyme-2, as a receptor for SARS-CoV-2, has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and in ammation which is decreasing with age [41]. This could results in a better prognosis of patients with younger age.…”