Coronaviruses in children: A review of potential mechanisms of childhood protection

Abstract

Aim The 2019 coronavirus disease (COVID‐19) has spread worldwide and the number of cases continues to rise exponentially. Epidemiologic reports indicate that severity of illness increases with age. However, the reasons behind the relative protection of children and infants are unclear. Whether the rationale is host‐related or virus‐dependent is important to determine since the latter could change with viral mutations. We review factors that could affect the susceptibility of children to the novel coronavirus. Methods We search publications indexed on PUBMED. Results Descriptions of the pathophysiology of current and previous coronavirus infections suggest several viral targets and immunomodulatory pathways affecting the severity of illness. There is limited evidence to suggest age‐variability of viral cell receptors and transmembrane co‐factors required for coronavirus entry and replication. However, the ensuing cytokine storm and the effect of higher melatonin in children are age‐dependent and could explain decreased disease variability in children. Conclusion We believe that current evidence suggests host factors can play a role in disease severity in children and thus may remain protective despite potential virus mutation in the future. However, we recognize and discuss avenues of future research that can further illuminate the reasons children are protected from severe COVID‐19 illness.

Comparison between SARS-CoV-2 positive and negative pneumonia in children: A retrospective analysis at the beginning of the pandemic

“…Accordingly, several restrictions were promptly implemented like in most parts of the world, which also affected the general medical practice and patients’ management all over the country[ 4 ]. Overall, COVID-19 in children is characterized by a milder clinical course, in terms of both clinical manifestations and risk of complications[ 5 ]. According to the report from the American Academy of Pediatrics, as of September 17 th , 2020 (thus, related to the first wave of pandemic), the proportion of pediatric COVID-19 diagnoses in the United States was only 10.3% of all the COVID-19 registered cases; the mortality rate in children was < 0.2%[ 6 ].…”

Pediatric COVID-19 Pneumonia

“…The ACE-2 protein is expressed in several tissue types but primarily on the surface of type 2 alveolar epithelial cells; these cells are also known to produce surfactant that prevents lung collapse and, therefore, are vital to the gas exchange function of the lungs. Increased expression of human ACE-2 has been shown to enhance disease severity in mice infected with SARS-CoV-1, indicating that ACE-2 dependent viral entry is critical for the infectious process [25].…”

“…The age-dependence of any of these elements may help explain the decreased clinical severity seen in children with COVID-19. [25] The immune response caused by SARS-CoV-2 infection is divided into two phases: first, an immune-protective phase and then an activation phase of the cytokine storm. The second phase causes more severe clinical manifestations.…”