The COVID-19 pandemic is having a profound impact on the health, social and economic well-being of people in Canada and around the world. To address vaccine disparity among vulnerable populations facing social-structural challenges, it is crucial to provide evidence-based information on the importance of completion of the recommended vaccination schedule. In this study, we investigated vaccination rates and variables as facilitators or barriers to COVID-19 vaccination among vulnerable populations living in Vancouver’s inner-city residents. On a weekly basis, a team (including health care providers [HCPs] and support staff) conducts a Community Pop-up Clinic (CPC) event at single room occupancy dwellings in Vancouver’s inner city to provide COVID-19 vaccine and/or related information. Participants also completed a survey about their COVID-19 vaccination status and COVID knowledge, including knowledge about COVID vaccination. We collected data from 892 CPC participants between January 2021–August 2023. The median age at baseline was 45 (IQR 36–55) years, with 317 (35.5 %) female and 285 (31.9 %) self-identified as Indigenous. Within the population, 512 (57.4 %) reported unstable housing and 441 (49.5 %) were active injection drug users. Regarding COVID-19 vaccinations, 235 (26.3 %) were unvaccinated, 119 (13.3 %) had received one dose of the COVID-19 vaccine, 432 (48.4 %) had received 2 doses, and 106 (11.8 %) had received at least 3 doses. Variables such as age (AOR 2.28, 95 % CI 1.37–3.80, p < 0.001) and HCV seropositivity (AOR 1.91, 95 % CI 1.20–3.04, p = 0.005) were significantly associated with higher odds of vaccination uptake. Conversely, unstable housing was significantly associated with a lower odds of vaccination uptake (AOR 0.53, 95 % CI 0.35–0.79, p = 0.002). Results from this study suggest that targeted community focused initiatives are crucial to address vaccine disparity among vulnerable populations living in Vancouver’s inner city facing unstable housing and drug use injection.
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