Research Reveals Why Children Experience Less Severe COVID-19

Differences in immune system responses and where those responses happen may explain why children infected with SARS-CoV-2 typically experience milder illness.

Early in the COVID-19 pandemic, health experts observed stark differences in illness severity between adults and children, even as new SARS-CoV-2 strains developed. For example, children tend to have milder COVID-19, while adults are more likely to experience severe forms of the disease.

Although scientists say immune system responses likely play a role, it’s still unclear why there’s such a difference in COVID severity between these age groups.

However, a study published on September 29 in the journal Cell may have uncovered why young children exhibit lower rates of severe COVID-19 than adults.

The research, co-funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), found that young children have a strong immune response to SARS-CoV-2 in their noses but not in their blood. This response is the opposite of what adults typically experience.

To conduct the study, investigators obtained weekly nasal swabs and intermittent blood draws from 81 infants and young children born to mothers enrolled in a Cincinnati Children’s study during their third trimester of pregnancy.

The scientists also collected weekly nasal swabs from 19 mothers with COVID and 19 without the illness and blood samples from 89 adults with COVID-19 and 13 without.

During the study period, 54 children developed mild COVID-19, and 27 tested negative for the SARS-CoV-2 virus. The children with COVID-19 were one month to almost four years old at the time of infection.

Using these nasal swabs and blood samples, the scientists examined the children’s immune responses to SARS-CoV-2. They found that when children became infected with the virus, they did not have high levels of inflammatory cytokines in their blood, which is different from adults, who typically have high blood levels of these proteins.

Inflammatory cytokines in the blood are associated with severe illness and death from COVID-19.

However, the nasal swab results showed that children had high levels of inflammatory cytokines and a powerful antiviral cytokine in their noses. This finding suggests that children’s immune systems may attack and subdue SARS-CoV-2 as soon as it enters the body through the nasal passages. And this could be why children are less likely to experience severe COVID-19.

Moreover, children produced antibodies to SARS-CoV-2 at levels that rose and remained high throughout the 300-day study period. In contrast, adults have antibodies at levels that spike for a few weeks, then gradually decline.

The researchers say these findings could lead to the development of new COVID-19 vaccine adjuvants that act much like the immune system responses of children by stimulating antibodies without causing potentially harmful inflammation in the blood.