Exposure risk was shown to have affected individual susceptibility and the epidemic spread of COVID-19. The dynamics of risk by and across exposure settings alongside the variations following the implementation of social distancing interventions are understudied. This study aims to examine the population's trajectory of exposure risk in different settings and its association with SARS-CoV-2 infection across 3 consecutive Omicron epidemic waves in Hong Kong. From March to June 2022, invitation letters were posted to 41,132 randomly selected residential addresses for the recruitment of households into a prospective population cohort. Through web-based monthly surveys coupled with email reminders, a representative from each enrolled household self-reported incidents of SARS-CoV-2 infections, COVID-19 vaccination uptake, their activity pattern in the workplace, and daily and social settings in the preceding month. As a proxy of their exposure risk, the reported activity trend in each setting was differentiated into trajectories based on latent class growth analyses. The associations of different trajectories of SARS-CoV-2 infection overall and by Omicron wave (wave 1: February-April; wave 2: May-September; wave 3: October-December) in 2022 were evaluated by using Cox proportional hazards models and Kaplan-Meier analysis. In total, 33,501 monthly responses in the observation period of February-December 2022 were collected from 5321 individuals, with 41.7% (2221/5321) being male and a median age of 46 (IQR 34-57) years. Against an expanding COVID-19 vaccination coverage from 81.9% to 95.9% for 2 doses and 20% to 77.7% for 3 doses, the cumulative incidence of SARS-CoV-2 infection escalated from <0.2% to 25.3%, 32.4%, and 43.8% by the end of waves 1, 2, and 3, respectively. Throughout February-December 2022, 52.2% (647/1240) of participants had worked regularly on-site, 28.7% (356/1240) worked remotely, and 19.1% (237/1240) showed an assorted pattern. For daily and social settings, 4 and 5 trajectories were identified, respectively, with 11.5% (142/1240) and 14.6% (181/1240) of the participants gauged to have a high exposure risk. Compared to remote working, working regularly on-site (adjusted hazard ratio [aHR] 1.47, 95% CI 1.19-1.80) and living in a larger household (aHR 1.12, 95% CI 1.06-1.18) were associated with a higher risk of SARS-CoV-2 infection in wave 1. Those from the highest daily exposure risk trajectory (aHR 1.46, 95% CI 1.07-2.00) and the second highest social exposure risk trajectory (aHR 1.52, 95% CI 1.18-1.97) were also at an increased risk of infection in waves 2 and 3, respectively, relative to the lowest risk trajectory. In an infection-naive population, SARS-CoV-2 transmission was predominantly initiated at the workplace, accelerated in the household, and perpetuated in the daily and social environments, as stringent restrictions were scaled down. These patterns highlight the phasic shift of exposure settings, which is important for informing the effective calibration of targeted social distancing measures as an alternative to lockdown.
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