Adults can be infected with different outcomes, from asymptomatic, mild, moderate to severe disease, and death. Children can also be infected by SARS-CoV-2, but most paediatric cases with laboratory-confirmed SARS-CoV-2 infection are mild; severe COVID-19 disease in children is rare.

Children are more vulnerable to other infections; thus, the important question arises—why are children less susceptible to COVID-19 disease compared with adults? So far, there is no evidence of a lower degree of expression or function of the SARS-CoV-2 receptor (namely ACE2) in children. Thus, studying the innate immune system of children might be the key to understanding protection against or susceptibility to SARS-CoV-2.

The immune preparedness of children to any novel pathogens, including, SARS-CoV-2 might be based on several factors. First, in the early phases of infection, natural antibodies play a most important role. Second, children have the ability to rapidly produce natural antibodies with broad reactivity that have not yet been selected and shaped by the reaction to common environmental pathogens. Third, when a novel pathogen challenges the immune system, CD27dull MBCs might play a crucial role being capable of a more rapid reaction than naive B cells. 

Evolution has endowed a survival advantage to children to combat known and unknown pathogens. The adult is also well protected by the balance of cells with high and low specificity. With ageing, malnutrition, immunosuppression, and co-morbid states, our immune system loses the ability to adapt to novelty. Although vaccines are the way forward, in emergency situations such as the COVID-19 pandemic, the investigation and use of immune tools that nature has endowed to children might improve management outcomes.