by Gertrud U. Rey
The prevalence of SARS-CoV-2, the virus that causes COVID-19, is steadily increasing around the world. Yet despite this unsettling fact, one statistic continues to hold true: most infected children experience mild symptoms, respond well to treatment, recover more quickly than adults, and have a better prognosis.
An initial report from China showed that only 965 out of 44,672 confirmed COVID-19 patients were under the age of 19. A letter to the editor of the New England Journal of Medicine reported only six cases of COVID-19 out of 366 hospitalized children. Only one of these children required admission to the intensive care unit, and all six patients recovered after an average of 8 days. According to the largest study of COVID-19 in children to date, more than 90% of children with laboratory-confirmed COVID-19 had asymptomatic, mild, or moderate disease. A comprehensive review of COVID-19 in children published on March 23 shows that even in Italy, the country with the highest number of COVID-19-related deaths so far, only 1.2% of patients were children, and none of these children died.
What is the reason for this low morbidity and mortality in children? Although the answer isn’t clear, there are a few possible explanations. Children are thought to have fewer underlying disorders and healthier respiratory tracts because of less exposure to cigarette smoke and air pollution. There is speculation that the non-specific, innate immune response that occurs upon an initial encounter with a pathogen is stronger in children. This type of immune response seems to be delayed in the elderly, and in an effort to “catch up,” may result in excessive inflammation, thereby ultimately causing more severe damage.
Another possible explanation is tied to angiotensin-converting enzyme 2 (ACE2), the host cell surface protein that serves as a receptor for SARS-CoV-2 entry into cells. ACE2 is prevalent on lung, kidney, intestinal, and arterial cells, where it normally controls blood pressure by regulating the volume of fluids in the body. ACE2 is also an important regulator of the immune response, especially in the context of inflammation. Some suggest that ACE2 is less mature in young children and thus may not function properly as a receptor for SARS-CoV-2. Furthermore, it is more abundant on cells of the lower respiratory tract, which is typically the site of severe COVID-19 disease. Consistent with this observation, data indicate that children experience more SARS-CoV-2 infections in the upper respiratory tract than the lower respiratory tract.
It has also been suggested that ACE2 is expressed more abundantly on senescent cells, which have stopped dividing and exist predominantly in the elderly. Considering that senescent cells are still metabolically active and contain all the factors necessary for virus replication, this hypothesis seems plausible.
It is also possible that early childhood vaccines provide some protective immunity against SARS-CoV-2. For example, a study from 2008 shows that the measles vaccine elicits neutralizing (virus-inactivating) antibodies against SARS-CoV, the virus responsible for the 2003 coronavirus epidemic. Immunity derived from childhood vaccines typically wanes with age, thereby possibly increasing the risk of severe COVID-19 in the elderly.
As is typical of newly emerging pathogens, many characteristics of the diseases they cause are largely unknown. As such, the exact reasons for why COVID-19 is less severe in children remain ambiguous. Hopefully the answer will become clearer as more data emerge over the next few months.