Risk of severe COVID-19 infection among adults with prior exposure to children

“Significance: Epidemiologic data consistently show strong protection for young children against severe COVID-19 illness. Several mechanisms have been proposed to explain this phenomenon, including cross-reactive immunity—in which prior exposure to non-SARS-CoV-2 coronaviruses that commonly infect children confers some resistance to severe COVID-19 illness. We identified 3,126,427 adults (24% [N = 743,814] with children ≤18, and 8.8% [N = 274,316] with youngest child 0–5 years) to assess whether parents of young children—who have high exposure to non-SARS-CoV-2 coronaviruses—may also benefit from potential cross-immunity. In a large, real-world population, exposure to young children was strongly associated with less severe COVID-19 illness, after balancing known COVID-19 risk factors. This epidemiologic signal suggests endemic coronavirus cross-immunity may play a role in protection against severe COVID-19 outcomes…

Discussion: We sought to determine whether adults who are at higher likelihood of having prior exposure to non-SARS-CoV-2 coronaviruses may be at decreased risk for severe COVID-19 illness compared to patients at otherwise similar risk of adverse COVID-19 outcomes. To do this, we examined a propensity-matched cohort of patients with pre-pandemic exposure to young children, a group with the highest rate of upper respiratory infections and the highest likelihood of passing them on to adults (12, 13, 16–18, 27, 28), and compared their rates of COVID-19 infection and rates of severe COVID-19 illness including hospitalization and need for ICU, to adults who did not have the same presumed level of exposure to small children and, by proxy, non-SARS-CoV-2 coronavirus infections. We found that exposure to young children was not associated with a reduction in COVID-19 infection rates, but was associated with protection against severe COVID-19 illness. Those without identifiable household exposure to children based on health insurance enrollment had a 27% higher rate of COVID-19 hospitalization and a 49% higher rate of COVID-19 hospitalization requiring ICU admission than those with young children, when calculating outcomes for severe illness relative to the total population within each subgroup. When severe 
COVID-19 outcomes were calculated as a proportion of those who contracted COVID-19 infection within each age and exposure group—in other words, the risk of a severe adverse COVID-19 outcome among adults with confirmed COVID-19—the findings were more dramatic, with a 49% higher rate of COVID-19 hospitalization and a 76% higher rate of COVID-19 hospitalization requiring ICU admission among those without exposure to young children. Our findings, based on data prior to the availability of COVID-19 vaccines, provide potential epidemiologic evidence to suggest the possibility that cross-immunity to non-SARSCoV-2 coronaviruses may provide a level of protection against severe COVID-19 illness.”