Seroprevalence of Coronavirus NL63 in Yamagata, Japan, Between 1976 and 2022

Advances in the epidemiology of seasonal coronavirus (CoV) are important for understanding CoV transmission dynamics and strengthening the strategies against emerging CoV infections. The epidemiology of CoV-NL63, a seasonal CoV discovered in 2003, is poorly understood, particularly before 2003. To analyze the seroprevalence of CoV-NL63 in Yamagata, Japan, we performed a microneutralization test using 146 to 379 serum samples collected from four age groups ranging from 0 to 4 years to ≥ 40 years in 1976, 1990, 2010, 2019, and 2022, as well as the Yamagata isolate. We only measured the neutralizing antibodies (NT Abs) against CoV-NL63, as methods for other seasonal CoVs had not yet been established. The total NT Ab-positive rate in each year was 68.0%-90.4%. The Ab-positive rates in 0-4-year age group were 21.3%-65.2% in each year, whereas the rates for individuals aged above 4 years old were between 73.3% and 100% throughout the study period. We do not understand the influence of cross-reactive immunity among seasonal CoVs. This study shows that seroprevalence against CoV-NL63 increased with age in the younger generation and then plateaued at a high level, suggesting that reinfection may occur and that CoV-NL63 was already transmitted among infants and children before CoV-NL63 had been identified.