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

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.