Time to endemicity of SARS-CoV-2 in a sentinel cohort in the Netherlands: findings from a prospective observational study.

Abstract

The speed at which SARS-CoV-2 reached endemicity, characterised by widespread population exposure, is unknown. As antibody levels wane over time, longitudinal studies are needed to assess the transition to endemicity. This study aimed to assess the time until SARS-CoV-2 reached full endemicity in the general human population using data from the Amsterdam Cohort Studies (ACS). The ACS is a prospective observational cohort study, whose participants were considered as a sentinel group for worldwide spread, as their behaviour related to the risk of respiratory infections was not substantially different from the Dutch or worldwide population. Data of 468 ACS participants living in or near the Amsterdam region, the Netherlands, were collected from Jan 1, 2020, to Dec 17, 2024. The participants were adult men having sex with men, who enrolled before 2020, remained HIV negative throughout the study period, provided at least one blood sample before March 1, 2021, and had more than one study visit since Jan 1, 2020. Participants with no serum samples collected before March 1, 2021, those who provided only one serum sample, or those with false-positive results were excluded. Blood samples were collected at 6-month intervals. Antibodies against SARS-CoV-2 nucleocapsid proteins induced by natural infection and not vaccination were measured using double-recognition ELISA. Before each study visit, participants completed an online self-administered questionnaire on their health. We estimated the incidence rate of SARS-CoV-2 seroconversion per 100 person-years from Jan 1, 2020, to Dec 17, 2024. Time to seroconversion was assessed using the Kaplan-Meier method, with sensitivity analyses evaluating alternative assumptions for the timing of seroconversion. Among 468 participants, 359 (77%) seroconverted, 97 (21%) were censored before Jan 1, 2024, and 12 (3%) remained seronegative for SARS-CoV-2 nucleocapsid antibodies. The Kaplan-Meier estimate of the proportion without seroconversion by 2024 was 6% (95% CI 4-9). Three of the 12 seronegative people self-reported SARS-CoV-2 infection during follow-up; the remaining nine people reported either no testing or only negative SARS-CoV-2 test results. Most infections (n=185) occurred between January and December, 2022, when omicron variants started circulating and mitigation measures were reduced. Almost 5 years after the start of the pandemic, most participants have developed antibodies to SARS-CoV-2 from natural infection, indicating SARS-CoV-2 reached endemicity within this period. Extrapolation of this finding implies that most people worldwide might have experienced at least one SARS-CoV-2 infection. Future emergence of another novel respiratory virus might also take only a few years to reach endemicity, although mitigation measures and vaccination might slow this transition. Center for Infectious Disease Control of the Netherlands National Institute for Public Health and the Environment.