Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.