The COVID-19 pandemic has simultaneously resulted in high global mortality and major economic disruptions. As a control measure, non-pharmaceutical interventions (NPIs) such as social distancing and mobility restrictions have been put in place worldwide and have successfully reduced transmission of the virus. However, these interventions are unsustainable in the long-term 4 and current hopes to control the pandemic rely heavily on vaccination.
In December 2020, the first vaccine against SARS-CoV-2 was approved; by March 2021, 12 vaccines had been licensed (https://vac-lshtm.shinyapps.io/ncov_vaccine_landscape/) and more than 300 million vaccination doses administered worldwide (https://ourworldindata.org/covid-vaccinations#). Their reported efficacy against symptomatic disease ranges from 50% to over 95% 5-9. Given the high basic reproduction number for SARS-CoV-2 (estimates range between 3-4)4 high levels of vaccine uptake will be required to achieve herd immunity3, particularly if children are not vaccinated during the first phase of roll-out.
One major concern that threatens to limit the impact of vaccination is vaccine hesitancy2. Population surveys have found that between 14% 10 and 27% 11 of adults say that they will not accept a vaccine if available, whilst between 14%10 and 19% 11 say that they are uncertain. There is a large variation in vaccine hesitancy between countries , with the proportion saying that they would get a SARS-Cov-2 vaccine if it became available, ranging from 40% for France 11 to 89% for China10. In many countries, vaccine hesitancy is heterogenous across sub-populations depending on gender, age, ethnicity, religion, or socioeconomic status 10-12 . The key drivers of SARS-CoV-2 vaccine hesitancy are related to concerns about the accelerated pace of vaccine development12 , side-effects11, and the spread of misinformation about the pandemic2.
To understand the likely impact of vaccine hesitancy on future control of the pandemic, we use a mathematical model of SARS-CoV-2 transmission3 to explore vaccine hesitancy through its impact on population coverage. We capture the effect of reduced coverage using three measured levels of vaccine hesitancy based on self-reported intention to be vaccinated from recent behavioural survey data11. Low, medium, and high hesitancy levels result in optimistic, neutral and pessimistic scenarios respectively. Hesitancy levels are further disaggregated by age-group to capture variation in attitudes with respect to age. The hesitancy scenarios are compared to an ideal counterfactual assuming no vaccine hesitancy, in which we assume that a small proportion (2%) of the population will be ineligible to be vaccinated due to contraindications. We model each scenario with both a high and a moderate vaccine efficacy profile that represents the range of efficacies of currently approved vaccines. Informed by current vaccine roll-out in high-income countries, we assume that vaccination started in January 2021 and is implemented at a rate that results in a total campaign of 10 months to fully vaccinate the population above 15 years old, with no vaccine hesitancy (the duration of the campaign is shorter in scenarios with vaccine hesitancy, due to assuming the same roll-out speed but lower uptake).
We first sought to determine the public health impact of vaccination and vaccine hesitancy as NPIs are lifted. To do so, we allowed the time-varying reproductive number in the absence of immunity Rt, to be increased in steps such that the effective reproductive number Reff, accounting for vaccine-induced immunity, remains at the threshold value of 1 with the assumption of ideal vaccination uptake (Figure 1 a, c). In this ideal scenario, NPIs can be fully lifted at the end of the vaccination period with a high efficacy vaccine (94% efficacy, Figure 1a). However, with a moderate efficacy vaccine (63% efficacy), some NPIs or other population-level behavioural changes may need to remain to control the epidemic (Figure 1 c). In the presence of vaccine hesitancy, lifting NPIs and relying on vaccine-induced immunity for control is predicted to lead to periodic outbreaks determined by the duration of naturally induced immunity, with the outbreak size greater at higher levels of vaccine hesitancy (Figure 1 b, d). For a high efficacy vaccine, even under the optimistic vaccine hesitancy scenario, daily deaths per million at the peak of the first outbreak are projected to be 8.7 times higher than under the ideal scenario (Figure 1b). This translates to a cumulative impact of 236 more deaths per million population in the two years after vaccination begins. For a vaccine of moderate efficacy, in an optimistic vaccine hesitancy scenario, the cumulative impact of vaccine hesitancy is projected to lead to 305 extra deaths per million population over this period. These adverse impacts of vaccine hesitancy on transmission, symptomatic disease, hospitalisations, and deaths affect vaccinated as well as unvaccinated individuals because of imperfect vaccine efficacy (Figure 2). Under the pessimistic scenario for vaccine hesitancy, the resulting lower vaccination coverage is projected to lead to a 33% and 46% increase in hospitalisations in the vaccinated population for the high and moderate vaccine efficacy profile, respectively, and a 18% and 46% increase in deaths in the vaccinated population, compared to an ideal vaccination scenario (Figure 2).
As an alternative way to assess the impact of vaccine hesitancy on the pandemic, we evaluated the degree to which other NPIs would need to remain in place given the real-time achieved vaccine coverage in order to prevent further epidemics (i.e. keep Reff<1, Figure 3). For the high efficacy vaccine, under the ideal scenario, we predict that NPIs could be fully lifted by the end of 2021 whilst keeping transmission under control. However, even under the optimistic scenario with low vaccine hesitancy, limited NPIs or other behavioural modifications might need to remain in place, with Rt having to remain below 2.4 to prevent further epidemics, 79% of the assumed R0 of 3. For the more pessimistic scenarios of vaccine hesitancy, and for lower vaccine efficacy, these differences become more pronounced. A difference of ~35% in the effective reproductive number could represent the closure of educational institutions or limiting interaction between households to achieve control of the epidemic13; both of which are not sustainable or desirable.
Our illustrative examples above are comparable to the waves of COVID-19 outbreaks in Europe. However, vaccine hesitancy varies between countries (Figure 4a). To evaluate the impact of these variations, we chose three European countries with different vaccine acceptance views: France, Germany, and the United Kingdom (UK). For each country, we modelled the trajectory of the pandemic under an ideal vaccination and a neutral vaccine hesitancy scenario. For a vaccine with high efficacy, we project 1.3, 4.5 and 8.7 times more deaths in 2021/2022 in a scenario with hesitancy compared to an ideal scenario in the UK, Germany and France respectively (Figure 4).
ur findings show the considerable impact of vaccine hesitancy, detailing the considerable mortality that could be averted with increased vaccine coverage. However, our analysis necessarily makes many simplifying assumptions, and it is important to note that the future trajectory of the epidemic will depend on the complex interactions between vaccination uptake, behaviour, and government interventions. First, we have assumed homogenous mixing between vaccine hesitant individuals. However, as has been seen for other diseases, COVID-19 vaccine hesitancy is heterogenous and clustered within population subgroups 14. Transmission is more likely to be sustained within clusters with low vaccine coverage 15,16 and therefore future outbreaks may be limited to these sub-populations. Secondly, self-reported attitudes to COVID-19 vaccines are changing over time 10,11 and levels may improve as confidence grows in the vaccination programmes. Thirdly, we do not account for immune escape from the vaccine due to new variants arising. Whilst second generation vaccines will likely become available to address this issue, it is currently unclear whether some of the high levels of vaccine uptake observed in early vaccine roll-outs would be sustained in subsequent booster programmes.
Getting vaccinated is an individual choice, but these individual choices have population wide effects that are likely to challenge current efforts to control COVID-19. Our findings suggest that vaccine hesitancy may have a substantial impact on the pandemic trajectory, deaths, and hospitalization. To prevent such adverse outcomes, NPIs would need to stay in place longer, or possibly indefinitely, resulting in high economic and social costs 17,18. Reducing vaccine hesitancy is therefore an important public health priority. Interventions that aim to build trust, for example with community-based public education or via positive role-models, are proven efficacious approaches to address hesitancy19. There is an ongoing debate about vaccine passports as a condition to travel, or a vaccination requirement for employees20. Such interventions may be effective because they incentivize individuals to get vaccinated, but they are controversial in libertarian democracies because they curtail personal freedom and individual choice about medical treatments. The alternative will be to accept some level of disease, hospitalisation and deaths given the level of vaccine coverage achieved whilst allowing NPIs to be lifted, given that NPIs are not a sustainable long-term method for control.