Waning Protection Against Severe COVID-19 Following Vaccination: A Longitudinal IPTW Analysis of Emergency Department...

The duration of protection that COVID-19 vaccination provides against severe outcomes remains uncertain. Accurately defining this timeframe is critical for informing effective vaccination policies and booster strategies. This investigation aimed to quantify the length and durability of vaccine-conferred protection against severe disease, delivering evidence to guide public health decision-making.

We conducted a multi-site cohort study to evaluate the relationship between time since last COVID-19 vaccination and the risk of severe infection among emergency department (ED) patients with a principal diagnosis of COVID-19. Vaccination status was categorized by time since the last documented dose: unvaccinated, 0-6 months, 7-12 months, 13-18 months, and 19-24 months. The primary outcome was severe COVID-19, defined as ICU admission, mechanical ventilation, or in-hospital death. Inverse Probability of Treatment Weighting (IPTW) was used to adjust for baseline confounding based on age group, sex, race, comorbidity burden, immunocompromised status, and calendar time period (pre-2023 vs. post-2023). Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for each vaccination interval compared to unvaccinated patients.

Between 1 December 2021, and 20 July 2024, 42,124 ED encounters were included in the analysis. In IPTW-weighted models, vaccination within 0-6 months (aHR 0.73, 95% CI 0.64-0.83), 7-12 months (aHR 0.72, 95% CI 0.64-0.82), and 13-18 months (aHR 0.67, 95% CI 0.57-0.79) was associated with a significantly reduced risk of severe outcomes. However, no significant protection was observed at 19-24 months (aHR 0.95, 95% CI 0.80-1.14). In age-stratified analyses, protection persisted longer in individuals aged ≥65 years than in those aged 50-64. Older age, male sex, comorbidities, and immunocompromised status were also associated with increased risk.

COVID-19 vaccination provides sustained protection against severe outcomes for up to 18 months, after which effectiveness declines substantially. These findings support booster dose strategies based on time since last vaccination and targeted prioritization for high-risk populations.