Long-term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission: A modelling study

Background Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus. Conclusions Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality. Author summary Why was this study done? Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus Disease 2019 (COVID-19), is now endemic globally. Vaccination remains important to reduce hospitalisations and deaths. Health authorities need to consider how frequently booster doses will be required and in which age groups. They also need to know the additional value of switching to vaccines that have been adapted to match more recently circulating variants of concern. What did the researchers do and find? We developed a mathematical model that captures the continued circulation and evolution of the SARS-CoV-2 virus in the presence of widespread infection-induced immunity from past exposure as well as vaccine-induced immunity from primary vaccination campaigns in 2021/2022. We used the model to explore different strategies for continued vaccination including the age group targeted, the frequency of boosting, and whether the vaccine was adapted to match more recent variants. In both high-income and low-middle-income settings, regardless of whether there was a high level of transmission in 2020/21 or a zero-COVID policy, we found that the most cost-effective vaccination strategy was to boost those at highest risk. We found that the current variant-adapted vaccines could avert nearly twice as many hospitalisations and deaths compared to the ancestral vaccines, and that updating these vaccines each year-as is done for seasonal influenza-could avert a further 30% of hospitalisations and deaths. What do these findings mean? Continued booster vaccinations will remain important to reduce both hospitalisations and deaths but should be targeted towards the highest risk groups. The estimates provided here can help to inform discussions around value for money by comparing the cost-effectiveness of COVID-19 vaccination to other health programmes. The precise values are limited by uncertainty as to whether the virus will continue to evolve, whether any new variants may emerge, and the additional protection provided by further booster doses given the widespread exposure of the population to infection.