Global impact of the first year of COVID-19 vaccination: a mathematical modelling study

The first COVID-19 vaccine was delivered outside of a clinical trial setting on Dec 8, 2020. By Dec 8, 2021, 55·9% of the global population was estimated to have received at least one dose of a COVID-19 vaccine, 45·5% estimated to have received two doses, and 4·3% estimated to have received a booster dose. Despite the incredible speed with which COVID-19 vaccines were developed in 2020 and subsequently distributed during 2021, more than 3·5 million deaths due to COVID-19 have been reported globally since the first vaccine was administered.

Understanding the global impact of vaccination on the course of the COVID-19 pandemic is challenging given the heterogeneous access to vaccines coupled with different levels of transmission and ongoing non-pharmaceutical interventions across countries. In the early months of 2021, the impact of vaccination would have been minimal because of the delay in developing the infrastructure for a widespread vaccination campaign, the need for a delayed two-dose regimen in some jurisdictions to ensure maximum protection, and the delay in the development of antibodies following vaccination. Additionally, as vaccine supply was constrained, most countries opted to prioritise vaccination in high-risk populations, including health-care workers and older people. Such strategies would have generated direct protection but would have had comparatively less impact on SARS-CoV-2 transmission. However, from mid-2021 onwards those countries with access to plentiful vaccine supply opted for mass vaccination of the adult population, later including children and subsequent boosting to maintain high levels of protection given the waning in vaccine efficacy and the emergence of new variants of concern. This approach has resulted in vast inequalities in global vaccine distribution.

Research in context

Evidence before this study

We searched PubMed up to April 26, 2022, without any date limits or language restrictions, using the search terms “vaccin* AND impact AND (death* OR live*) AND (estimat* OR evaluat*) AND (COVID-19 OR SARS-CoV-2)”. We found eight published studies that estimated the impact of COVID-19 vaccination, including deaths averted from vaccination. None of the studies considered the global impact of COVID-19 vaccination, focusing instead on specific regions (Italy, California, North Carolina, Stockholm, subsets of states in the USA, New York City, and the WHO European Region). Furthermore, the study focusing on the WHO European region only quantified the direct impact of vaccination and did not estimate the indirect effects (ie, decreasing infection risk of both vaccinated and unvaccinated susceptible individuals).

Added value of this study

This mathematical modelling study advances previous work both in terms of scale (number of regions modelled) and in terms of quantifying both the direct and indirect impact of COVID-19 vaccination globally. We estimated the impact of vaccination up to Dec 8, 2021, by fitting COVID-19 transmission models to both reported deaths and excess mortality during the pandemic as a proxy for deaths due to COVID-19. This study is, to the best of our knowledge, the first to use excess mortality estimates in this way, allowing for the impact of COVID-19 vaccination to be estimated more accurately in countries with weaker surveillance systems.

Implications of all the available evidence

The results highlight the substantial impact that vaccination has had on the trajectory of the COVID-19 pandemic. They also illustrate the broader impact of COVID-19 vaccination in terms of allowing countries with high vaccine coverage to relax interventions. Furthermore, the findings highlight the importance of equitable access to vaccines, particularly in low-income regions, where substantially more lives could have been saved if the vaccination targets set out by the COVID-19 Vaccines Global Access (COVAX) Facility (20% coverage in COVAX Advance Market Commitment countries by the end of 2021) and WHO (40% coverage in each country by the end of 2021) had been reached.

To reduce inequality, a fair allocation mechanism for COVID-19 vaccines was developed through the COVID-19 Vaccines Global Access (COVAX) facility, with a key target of achieving 20% vaccine coverage for the countries covered by its Advance Market Commitment (AMC) through COVAX-secured doses by the end of 2021. WHO expanded this target by setting a global strategy to achieve 70% coverage in all countries by mid-2022, with an interim target of 40% coverage by the end of 2021. However, as a result of numerous challenges, particularly the constrained vaccine supply to COVAX (exacerbated by some countries obtaining a greater proportion of the global vaccine supply, pharmaceutical companies not meeting their contractual obligations to COVAX, and unpredictable delays in supply including vaccines with brief expiry windows), these targets were not reached in many lower-middle-income countries and low-income countries. Vaccine uptake has also been suboptimal in many countries because of vaccine hesitancy. This considerable heterogeneity in vaccination coverage has resulted in continued reliance on non-pharmaceutical interventions for pandemic management in some countries but concomitantly enabled other nations to relax interventions as a route out of the pandemic.

Quantifying the impact of vaccination is further challenged by the incomplete picture of the COVID-19 pandemic that is obtained from reported deaths. In many countries, vital registration systems are incomplete and therefore only a fraction of deaths are routinely reported. However, even in countries with complete vital registration systems, it is difficult to accurately define the cause of death in individuals who present with multiple morbidities. Excess all-cause mortality (the difference between the observed and expected number of deaths in non-pandemic years) has therefore been used to quantify the impact of the COVID-19 pandemic. Although the exact contribution of COVID-19 to excess mortality is unknown, the strong temporal correlation observed globally between reported COVID-19 mortality and excess mortality provides evidence that excess mortality is an informative indicator of pandemic-related mortality. Robust vital registration systems do not exist in many parts of the world, with WHO estimating that 40% of global deaths that occurred in 2020 were unregistered, and therefore data on excess mortality are not available for every country. Model-based estimates have therefore been developed to obtain a more complete estimate of the pandemic to date. One set of estimates produced by The Economist uses a range of socioeconomic and epidemiological data to infer excess mortality. Although the precise estimates differ between research groups and WHO, they all suggest a substantially larger number of COVID-19 deaths than have been reported to date.

We aimed to quantify the global impact of the first year of COVID-19 vaccination and estimate the number of deaths from COVID-19 averted in 185 countries and territories, both from the direct protection of vaccinated individuals and from the indirect protection of all individuals living in vaccinated environments due to the reduction in risk of infection. Additionally, we aimed to quantify the impact that a more equitable global vaccination campaign, meeting the vaccination targets set by COVAX of 20% vaccination coverage of the eligible population by the end of 2021, could have had in COVAX AMC countries. We also aimed to quantify the impact of achieving the WHO target of 40% coverage by the end of 2021 in all countries.