Why COVID-19 is less frequent and severe in children: a narrative review

Abstract

Background Despite the streaks of severity, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is, in general, less frequent and severe in children than in adults. We searched for causal evidence of this mystery. Data sources An extensive search strategy was designed to identify papers on coronavirus disease 2019 (COVID-19). We searched Ovid MEDLINE, PubMed, EMBASE databases, and Cochrane library and carried out a review on the causes of this dilemma. Results Our searches produced 81 relevant articles. The review showed that children accounted for a lower percentage of reported cases, and they also experienced less severe illness courses. Some potential explanations, including the tendency to engage the upper airway, the different expression in both receptors of angiotensin-converting enzyme and renin-angiotensin system, a less vigorous immune response, the lower levels of interleukin (IL)-6, IL-10, myeloperoxidase, and P-selectin and a higher intracellular adhesion molecule-1, a potential protective role of lymphocytes, and also lung infiltrations might have protective roles in the immune system-respiratory tract interactions. Finally, what have shed light on this under representation comes from two studies that revealed high-titer immunoglobulin-G antibodies against respiratory syncytial virus and mycoplasma pneumonia, may carry out cross-protection against SARS-CoV-2 infection, just like what suggested about the vaccines. Conclusions These results require an in-depth look. Properties of the immune system including a less vigorous adaptive system beside a preliminary potent innate response and a trained immunity alongside a healthier respiratory system, and their interactions, might protect children against SARS-CoV-2 infection. However, further studies are needed to explore other possible causes of this enigma.

The Relationship between COVID-19 and Innate Immunity in Children: A Review

“…Although a decrease in CD4+ T cells was common in adult patients with severe and moderate COVID-19, this finding was rarely seen in children. At birth, there is a greater secretion capacity of IL-10, a cytokine capable of inhibiting inflammatory processes, while in the following years, a greater balance between T helper (Th) 1/Th2/Th17 lymphocytes develops; this finding, described as the immunosenescence phenomenon, helps to explain the different immunological response in adults compared with pediatric patients [ 37 , 38 ].…”

Managing children with brain tumors during the COVID-19 era: Don’t stop the care!

“…Previous studies have demonstrated that some coronaviruses, such as SARS-CoV-2, bind to angiotensin-converting enzyme-2 (ACE2) cell receptors in humans. However, ACE2 expression in the rat lung reduces dramatically with age, a finding seemingly in contrast with the low susceptibility of children to COVID-19 [3] , [14] .…”

“…To increase the resources, such as hospitals beds and medical staff, procedures deemed elective or non-urgent have been delayed, postponed, or canceled. Based on data regarding the COVID-19 outbreak first in China and then worldwide, children aged less than 10 years old have been found to exhibit significantly lower susceptibility to SARS-CoV-2 infection compared to adults [3] , [4] .…”

COVID-19 in Children With Liver Disease

“…Seven of the 36 patients (mean age 5years) were positive for Mycoplasma pneumoniae and another 6/36 were positive for the human metapneumovirus on nasopharyngeal swabs. Studies have further shown children testing negative for SARS-CoV-2 had higher IgG antibody titres against Respiratory syncytial virus (RSV) and/or M. pneumoniae ( 32 ). These findings support the theory that common childhood infections may offer cross protection ( 33 ).…”