Background: Children experience lower rates of symptomatic and severe coronavirus disease 2019 (COVID-19) than adults, potentially due to cross-reactive immunity from prior endemic human coronavirus (HCoV) infections. However, epidemiologic longitudinal evidence supporting this mechanism in children remains limited. In 2021, outbreaks of HCoV-NL63 and HCoV-OC43 occurred in Furano, Japan. Methods: This prospective longitudinal cohort study was conducted at a single hospital in Furano. The primary outcome was time to onset of symptomatic COVID-19. Children with HCoV-NL63 (weeks 1–21) or HCoV-OC43 (weeks 22–33) infections were compared with children infected with other respiratory viruses. Analyses included Kaplan–Meier estimation, log-rank tests, and multivariate Cox regression. Results: A total of 237 children were followed for up to 700 days. Cumulative incidence analyses demonstrated a significantly reduced risk of symptomatic COVID-19 in the HCoV-NL63 group through day 700 ( P = 0.03), whereas no protective effect was observed for HCoV-OC43. In multivariable analyses, prior HCoV-NL63 infection was associated with significant protection at 500 days (95% confidence interval CI: 0.05–0.54), 600 days (95% CI: 0.07–0.45), and 700 days (95% CI: 0.19–0.80), but not at earlier time points. HCoV-OC43 showed no significant association at any time point. Conclusions: Prior HCoV-NL63 infection, but not HCoV-OC43, was associated with reduced risk of symptomatic COVID-19 in children for up to 700 days. These findings provide epidemiologic support for virus-specific cross-reactive immunity and highlight pediatric–adult differences. These findings are not yet generalizable and require validation in studies using serological markers and stricter confounder control.
Kakuya et al. (Fri,) studied this question.