***This article is published as a preprint.***
Abstract
Background
The recent Omicron-related waves of the COVID-19 pandemic have resulted in unprecedented levels of population transmission due to the variant's high level of infectiousness across most of the world. China, the last large country to end its "zero-COVID" policies, is currently facing its own massive Omicron-related wave, and the final impact of that wave remains uncertain. We have seen repeatedly that the epidemiological characteristics of new variants can have profound impacts on global health outcomes. While the characteristics of these new variants are difficult to predict ahead of their emergence, considering the impact of potential future scenarios is of central importance for prudent planning and policy making. This paper samples across a range of potential variant-level characteristics to provide global forecasts of infections, hospitalisations, and deaths in the face of ongoing Omicron-related transmission and waning levels of past immunity and evaluates a range of interventions that may diminish the impact of future waves.
Methods
We created a susceptible-exposed-infectious dynamic model that accounts for vaccine uptake and effectiveness, antiviral administration, the emergence of new variants, and waning protection from both infection- and vaccine-derived immunity. Using this model, we first estimated past infections, hospitalisations, and deaths by variant, location, and day. We used these findings to more fully understand the global progression of the COVID-19 pandemic through December 12, 2022. Second, we forecasted these same outcome measures under five potential variant emergence scenarios. Third, we evaluated three different interventions in isolation and in concert within each potential variant scenario, to assess the impact of available intervention strategies through June 30, 2023.
Findings
We estimated that from November 15, 2021, through December 12, 2022, there were 8.60 billion (95% uncertainty interval [UI] 6.37-11.7) SARS-CoV-2 infections, 13.1 million (10.6-16.5) hospitalisations, and 3.04 million (2.65-3.55) deaths, the majority of which were attributable to Omicron variants (98.5% [97.4-99.1] of infections, 82.6% [76.7-86.3] of hospitalisations, and 72.4% [66.4-76.0] of deaths). Compared to the pre-Omicron pandemic period from January 1, 2020, to November 15, 2021, we estimated that there were more than twice as many infections (214% [163-286]) globally from November 15, 2021, to December 12, 2022, but only 20.6% (19.8-21.4) of the estimated deaths. The massive Omicron waves and high vaccination rates in many high-income countries have together contributed to high levels of immunity against SARS-CoV-2 infection, leaving only 97.3% (96.3-98.2) of the global population with no protection as of December 1, 2022.
Concurrently, however, China, where only 17.6% [5.28-34.8] of the population have ever experienced infection due to its zero-COVID policy, requires special attention over the next few months, as all our future scenarios predict substantial increases in transmission, hospitalisation, and death in China in now that zero-COVID policies have been relaxed. Under the future scenario we consider most plausible (a scenario with another new Omicron-like variant emerging and reference levels of the drivers of transmission), we estimated there will be an additional 5.19 billion (3.11-7.78) infections, 13.6 million (8.50-21.8) hospitalisations, and 2.74 million (1.40-5.68) deaths between December 12, 2022, and June 30, 2023, with the Western Pacific region projected to sustain the highest rates of additional deaths, driven primarily by the uncontained outbreak in China.
By comparison, a baseline scenario in which no new variant emerges results in 3.54 billion (2.24-5.43) infections, 6.26 million (4.11-9.65) hospitalisations, and 1.58 million (0.829-3.95) deaths in the same forecast period. The ability for a new variant to break through past infection- and vaccine-derived immunity greatly influences future outcomes: we estimate a new variant with the high severity of Delta, but correspondingly moderate immunity breakthrough rates will have difficulty overtaking current variants and will result in similar outcomes to the Omicron-like variant scenario with 3.64 billion (2.26-5.83) new infections, 7.87 million (4.81-13.0) new hospitalisations, and 2.87 million (1.03-5.56) new deaths.
Finally, if we consider a variant that combines the high infectiousness and breakthrough rates of Omicron with the high severity of Delta, we again estimate 5.19 billion (3.11-7.78) new infections, but due to the presumed increase in severe outcomes, we estimate 30.2 million (13.4-51.2) new hospitalisations and 15.9 million (4.31-35.9) deaths over the forecasted period. The impacts of interventions vary by variant characteristics and region of the world, with increased mask usage and reimplementation of some mandates having massive impact in some regions while having less impact in others. Finally, assuming variant spread was as rapid as observed for Omicron, we find almost no impact of a rapidly developed and deployed variant-targeted booster.
Interpretation
As infection-derived and vaccine-conferred protection wanes, we expect infections to rise, but as most of the world's population has some level of immunity to SARS-CoV-2 as of December 12, 2022, all but the most pessimistic forecasts in this analysis do not predict a massive global surge by June 30, 2023. Paradoxically, China, due to its lower levels of population immunity and effective vaccination will likely experience substantial numbers of infections and deaths that, due to its large population size, will adversely affect the global toll. This could be substantially mitigated by existing intervention options including masking, vaccination, health-care preparedness, and effective antiviral compounds for those at most at risk of poor outcomes. While still resulting in morbidity and mortality, this endemic transmission provides protection from less transmissible variants and particularly protects against sub-lineages of the more severe pre-Omicron variants. In the scenarios where a new variant does emerge and spread globally, however, the speed of this spread may be too fast to rely on even the most quickly developed mRNA vaccines to provide protection soon enough.
Existing vaccines and boosters have played an important role in increasing immunity worldwide, but the continued contribution of mask usage (both past and future) in the prevention of infection and death cannot be understated. The characteristics of future COVID-19 variants are inherently difficult to predict, and our forecasts do show considerable differences in outcomes as a function of these variant properties. Given the uncertainty surrounding what type of variant will next emerge, the world would be wise to remain vigilant in 2023 as we move to the next phase of the COVID-19 pandemic.
Funding Statement
Funding was provided by the Bill & Melinda Gates Foundation, J. Stanton, T. Gillespie, and J. and E. Nordstrom. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or the writing of the report. Members of the core research team for this topic area had full access to the underlying data used to generate estimates presented in this paper. All other authors had access to, and reviewed, estimates as part of the research evaluation process.
