SARS-CoV-2 Cumulative Infection Over the Pandemic and Its Associated Factors Among Healthcare Workers in Japan

Evidence is scarce on cumulative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections among healthcare workers during the pandemic. This study aimed to describe cumulative infections, including undiagnosed cases, and identify factors associated with infection in healthcare workers in Japan.

Using serosurveys conducted across six national centers in Japan, we tracked coronavirus disease 2019 (COVID-19) cumulative infections. Seropositivity was defined as a positive result for SARS-CoV-2 nucleocapsid protein using the Roche assay, and cumulative infection was defined as the proportion of participants who tested positive for anti-nucleocapsid antibodies and/or self-reported a history of laboratory-confirmed or clinically diagnosed COVID-19 since the start of the pandemic. A robust Poisson regression model was used to investigate factors associated with infection risk as of September 2023.

Cumulative infection, which was less than 5% until the end of 2021, increased after the emergence of the Omicron variant. Specifically, cumulative infection reached 14.6% in July 2022 (BA.1/2), 37.4% in December 2022 (BA.5), 53.3% in September 2023 (XBB subvariants), and 71.5% in December 2023 (JN.1 subvariant). The proportion of undiagnosed cases detected by antibody testing alone, without a prior diagnosis, decreased from 60.9% in December 2020 to 24.7% in December 2023. Individuals aged 50 to 59 years (prevalence ratio [PR] 0.73; 95% confidence interval [CI], 0.67-0.79) and 60 years or older (PR 0.67; 95% CI, 0.59-0.77) had lower cumulative infections than those aged under 30 years old. Physicians and nurses had significantly higher cumulative infections than administrative staff, with fully adjusted PR of 1.09 (95% CI, 1.01-1.18) and 1.18 (95% CI, 1.08-1.30), respectively.

Among healthcare workers in Japan, cumulative SARS-CoV-2 infection markedly increased after the emergence of the Omicron variant, whereas the proportion of undiagnosed cases has decreased throughout the pandemic. Younger people (<50 years), as well as physicians and nurses, have faced a higher risk of infection.