Direct impact of COVID-19 vaccination in Chile: averted cases, hospitalizations, ICU admissions, and deaths

As of November 2023, the COVID-19 pandemic has resulted in over 772 million cases and 6.98 million deaths worldwide [1]. In Chile, more than 5.3 million cases and 62,000 deaths have been reported [2]. At the beginning of the pandemic, the country implemented non-pharmaceutical interventions, such as school and university closures, lockdowns, cordons sanitaires, and curfews [3]. Measures such as social distancing, hand sanitization and mask-wearing were also instituted, the latter remaining in effect until the end of September, 2022 [4]. Furthermore, in response, Chile underwent one of the most rapid and extensive vaccination campaigns in the world [5]. This began at the end of December 2020, with the immunization of healthcare workers, followed by a massive campaign to vaccinate the general population prioritized by age and comorbidity, which started in February 2021. Chile was also among the first countries to initiate a booster-vaccination campaign, which started in early August 2021. Originally aimed at individuals who had received the full CoronaVac vaccination, the booster-vaccination campaign was later expanded to include all fully vaccinated individuals. Adherence by the population to the vaccination program was remarkably high; by the end of 2021, 84% of the country's 19.5 million inhabitants had received a full course of vaccination while 56% had received a booster dose. Vaccination coverage has continued to increase during 2022 and 2023; as at October 2, 2023, 94.3% of the population aged 18 years and older has completed a primary course of vaccination (one or two doses, according to the protocol for administering each vaccine), 93.1% have received a booster dose, and 82.5% had received a fourth dose [6].

Chile experienced successive waves of COVID-19 cases (Fig. 1). The first of these began in March 2020 with the original strain of COVID-19, followed by a important wave due to the Gamma and Lambda variants between February and August of 2021. Subsequently, a wave driven by the Delta variant emerged in mid-August 2021. In January 2022, the Omicron variant started to spread in Chile and this remains the dominant variant today [7].

Assessments of the impact of SARS-CoV-2 vaccination campaigns have been conducted predominantly in high-income nations, where mRNA vaccines have been extensively employed [8‐12]. CoronaVac, an inactivated virus vaccine, has been widely used in Chile. As at July 2, 2022, it accounted for 43.9% of administered doses. Other vaccines, including BNT162b2, mRNA-1273, ChAdOx1, Ad5-nCoV and Ad26.COV2.S, were also administered. To our knowledge, there are few studies measuring the direct impact of vaccination in a country where the CoronaVac vaccine has been widely deployed [13].

Earlier research in Chile has evaluated the effectiveness of the CoronaVac vaccine during the initial phases of the vaccination campaign [14], as well as the antibody response elicited by CoronaVac compared to individuals who received the BNT162b2 vaccine [15]. Despite the remarkable scope of Chile's vaccination campaign, its overall impact remains unknown. One international study has estimated the number of lives saved during the first year of global vaccination with a particular focus on Chile [16], but it drew upon limited data from Chile and made substantial assumptions about vaccine effectiveness, which is challenging to determine in Chile due to the number of vaccines deployed and differences in how much their effectiveness have been studied.

Quantifying averted outcomes attributable to the vaccination campaign nationally would be valuable, not only for helping to assess the benefits of vaccination but also for informing the design of mass vaccination campaigns in response to future pandemics. In this study, we take advantage of comprehensive data on COVID-related outcomes, categorized by age group and vaccine-administration schedules, to accurately estimate the direct impact of the first year and a half (December 20, 2020 - July 2, 2022) of vaccination in terms of cases, hospitalizations, intensive-care-unit (ICU) admissions and deaths averted in Chile in individuals aged 16 years and older.

We employed a method that directly assesses the impact of the vaccination program by comparing the weekly incidence of various outcomes between vaccinated and unvaccinated individuals over time, similar to the approaches taken in Israel and Brazil [8, 13]. The results of our study demonstrate the substantial impact of Chile's vaccination campaign in reducing the burden of COVID-19 in terms of cases, hospitalizations, ICU admissions and deaths during the first year and a half of the campaign. We estimate that vaccination efforts prevented 26% of cases, 66% of hospitalizations, 70% of ICU admissions, and 67% of deaths among individuals aged 16 years or older during the study period. Notably, the most significant reductions were observed for the severe outcomes of hospitalization, ICU admission and death, shedding light on the critical role vaccination has played in mitigating the severity of COVID-19.

Our findings also revealed that the complete vaccination with 2 doses had an important impact on preventing COVID-19-related severe outcomes, emphasizing the importance of completing the full course of vaccination. Moreover, the first-booster (third-dose) campaign contributed to further reductions in cases and severe outcomes during the Delta variant wave, which supports the role of booster doses in prolonging vaccine effectiveness.

It is important to note that individuals over 55 years old, who represented 30% of the Chilean population of at least 16 years of age, accounted for the majority of prevented hospitalizations, ICU admissions and deaths. This observation highlights the effectiveness of Chile's age-based prioritization strategy in targeting the most vulnerable populations and reducing the overall burden on healthcare systems.

Our estimations of averted outcomes are robust to hypothesis on the population susceptible (sensitivity analysis 1), but are sensitive to the census data on which we base our calculation of the size of the unvaccinated population (sensitivity analysis 2).

Watson et al. [16] conducted an international study to evaluate the number of deaths averted by COVID-19 vaccination in 185 countries and territories, with a focus on Chile. They estimated that between December 8, 2020, and December 8, 2021, 108,100 (94,170 - 121,800) and 146,100 (137,200 - 163,700) deaths were averted in Chile based on COVID-19-related deaths and excess mortality, respectively. These estimates are higher than our estimates of deaths averted, which cover a longer period. This is due firstly to the fact that we focus solely on the direct effect of vaccination whereas Watson et al. take into account the effect of reduced transmission among vaccinated individuals. However, they make assumptions about vaccine effectiveness based on studies of other vaccines and variants [22], as such studies were not available for Coronavac. If Coronavac is less effective at preventing transmission than mRNA vaccines, this could lead to an overestimation of the number of averted deaths.

To the best of our knowledge, the only publication addressing events averted in a country that made extensive use of the CoronaVac vaccine is Santos et al. [13], who estimated that 82% of COVID-19-related deaths were averted in Brazil between January 17, 2021, and January 31, 2022. This is higher than our estimate of 67%. The discrepancy may be attributed to differences in the study period, types of vaccines used, as well as the influence of geography and regional policies for managing the epidemic within the two countries.

In the Additional file 1, we showed the connection between our approach and a conventional method employed to assess vaccination impact through vaccine effectiveness [15‐18]. However, we were unable to use this method due to unavailability of comprehensive data on vaccine effectiveness for the different types of vaccines, number of doses, against different variants for all vaccines deployed in Chile.

Our study is not without limitations. First of all, we have not taken into account the indirect impact of vaccination due to reduced transmission among vaccinated individuals. However, this would require precise knowledge of vaccine effectiveness against transmission and infection against each variant for each vaccine. To our knowledge, such data are not available in the literature. Although our methodology based on comparing incidence rates between vaccinated and unvaccinated populations allows us to avoid making assumptions about vaccine effectiveness, it is still subject to potential biases. It was not possible to account for confounding variables such as co-morbidities, socioeconomic strata and testing rates, etc. Furthermore, we did not consider any difference in detection rates between vaccinated and unvaccinated subjects, which may skew the estimate of averted cases, but probably has less impact on estimates of severe outcomes averted. Finally, we should note that our method can lead to negative estimates in the number of cases averted (Table 1). The diminished effectiveness of initial vaccine generations against the Omicron strain, coupled with the waning effectiveness of vaccines over time [23], could partially account for this phenomenon. Additionally, vaccinated individuals may exhibit behaviors that put them at a higher risk of infection compared to their unvaccinated counterparts.

This study shows Chile's vaccination campaign sharply reduced the burden of COVID-19. Our findings underscore the importance of widespread vaccination, particularly among vulnerable populations, in controlling the pandemic and alleviating the strain on healthcare systems.