Cryptic transmission of SARS-CoV-2 and the first COVID-19 wave.

Considerable uncertainty surrounds the timeline of introductions and onsets of local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) globally1-7. Although a limited number of SARS-CoV-2 introductions were reported in January and February 2020 (refs.8,9), the narrowness of the initial testing criteria, combined with a slow growth in testing capacity and porous travel screening10, left many countries vulnerable to unmitigated, cryptic transmission. Here we use a global metapopulation epidemic model to provide a mechanistic understanding of the early dispersal of infections and the temporal windows of the introduction of SARS-CoV-2 and onset of local transmission in Europe and the USA. We find that community transmission of SARS-CoV-2 was likely to have been present in several areas of Europe and the USA by January 2020, and estimate that by early March, only 1 to 4 in 100 SARS-CoV-2 infections were detected by surveillance systems. The modelling results highlight international travel as the key driver of the introduction of SARS-CoV-2, with possible introductions and transmission events as early as December 2019 to January 2020. We find a heterogeneous geographic distribution of cumulative infection attack rates by 4 July 2020, ranging from 0.78% to 15.2% across US states and 0.19% to 13.2% in European countries. Our approach complements phylogenetic analyses and other surveillance approaches and provides insights that can be used to design innovative, model-driven surveillance systems that guide enhanced testing and response strategies.

Multimodeling approach to evaluating the efficacy of layering pharmaceutical and nonpharmaceutical interventions for influenza pandemics.

When an influenza pandemic emerges, temporary school closures and antiviral treatment may slow virus spread, reduce the overall disease burden, and provide time for vaccine development, distribution, and administration while keeping a larger portion of the general population infection free. The impact of such measures will depend on the transmissibility and severity of the virus and the timing and extent of their implementation. To provide robust assessments of layered pandemic intervention strategies, the Centers for Disease Control and Prevention (CDC) funded a network of academic groups to build a framework for the development and comparison of multiple pandemic influenza models. Research teams from Columbia University, Imperial College London/Princeton University, Northeastern University, the University of Texas at Austin/Yale University, and the University of Virginia independently modeled three prescribed sets of pandemic influenza scenarios developed collaboratively by the CDC and network members. Results provided by the groups were aggregated into a mean-based ensemble. The ensemble and most component models agreed on the ranking of the most and least effective intervention strategies by impact but not on the magnitude of those impacts. In the scenarios evaluated, vaccination alone, due to the time needed for development, approval, and deployment, would not be expected to substantially reduce the numbers of illnesses, hospitalizations, and deaths that would occur. Only strategies that included early implementation of school closure were found to substantially mitigate early spread and allow time for vaccines to be developed and administered, especially under a highly transmissible pandemic scenario.

Quantifying the importance and location of SARS-CoV-2 transmission events in large metropolitan areas.

Detailed characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission across different settings can help design less disruptive interventions. We used real-time, privacy-enhanced mobility data in the New York City, NY and Seattle, WA metropolitan areas to build a detailed agent-based model of SARS-CoV-2 infection to estimate the where, when, and magnitude of transmission events during the pandemic's first wave. We estimate that only 18% of individuals produce most infections (80%), with about 10% of events that can be considered superspreading events (SSEs). Although mass gatherings present an important risk for SSEs, we estimate that the bulk of transmission occurred in smaller events in settings like workplaces, grocery stores, or food venues. The places most important for transmission change during the pandemic and are different across cities, signaling the large underlying behavioral component underneath them. Our modeling complements case studies and epidemiological data and indicates that real-time tracking of transmission events could help evaluate and define targeted mitigation policies.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

Anatomy of the first six months of COVID-19 vaccination campaign in Italy.

We analyze the effectiveness of the first six months of vaccination campaign against SARS-CoV-2 in Italy by using a computational epidemic model which takes into account demographic, mobility, vaccines data, as well as estimates of the introduction and spreading of the more transmissible Alpha variant. We consider six sub-national regions and study the effect of vaccines in terms of number of averted deaths, infections, and reduction in the Infection Fatality Rate (IFR) with respect to counterfactual scenarios with the actual non-pharmaceuticals interventions but no vaccine administration. Furthermore, we compare the effectiveness in counterfactual scenarios with different vaccines allocation strategies and vaccination rates. Our results show that, as of 2021/07/05, vaccines averted 29, 350 (IQR: [16, 454-42, 826]) deaths and 4, 256, 332 (IQR: [1, 675, 564-6, 980, 070]) infections and a new pandemic wave in the country. During the same period, they achieved a -22.2% (IQR: [-31.4%; -13.9%]) IFR reduction. We show that a campaign that would have strictly prioritized age groups at higher risk of dying from COVID-19, besides frontline workers and the fragile population, would have implied additional benefits both in terms of avoided fatalities and reduction in the IFR. Strategies targeting the most active age groups would have prevented a higher number of infections but would have been associated with more deaths. Finally, we study the effects of different vaccination intake scenarios by rescaling the number of available doses in the time period under study to those administered in other countries of reference. The modeling framework can be applied to other countries to provide a mechanistic characterization of vaccination campaigns worldwide.

Estimating the cumulative incidence of COVID-19 in the United States using influenza surveillance, virologic testing, and mortality data: Four complementary approaches.

Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 in each state in the US as well as Puerto Rico and the District of Columbia, using a combination of excess influenza-like illness reports, COVID-19 test statistics, COVID-19 mortality reports, and a spatially structured epidemic model. Instead of relying on the estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our four approaches emerges the consistent conclusion that on April 4, 2020, the estimated case count was 5 to 50 times higher than the official positive test counts across the different states. Nationally, our estimates of COVID-19 symptomatic cases as of April 4 have a likely range of 2.3 to 4.8 million, with possibly as many as 7.6 million cases, up to 25 times greater than the cumulative confirmed cases of about 311,000. Extending our methods to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 4.9 to 10.1 million, as opposed to 1.5 million positive test counts. The proposed combination of approaches may prove useful in assessing the burden of COVID-19 during resurgences in the US and other countries with comparable surveillance systems.

Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021.

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

Spread of Zika virus in the Americas.

We use a data-driven global stochastic epidemic model to analyze the spread of the Zika virus (ZIKV) in the Americas. The model has high spatial and temporal resolution and integrates real-world demographic, human mobility, socioeconomic, temperature, and vector density data. We estimate that the first introduction of ZIKV to Brazil likely occurred between August 2013 and April 2014 (90% credible interval). We provide simulated epidemic profiles of incident ZIKV infections for several countries in the Americas through February 2017. The ZIKV epidemic is characterized by slow growth and high spatial and seasonal heterogeneity, attributable to the dynamics of the mosquito vector and to the characteristics and mobility of the human populations. We project the expected timing and number of pregnancies infected with ZIKV during the first trimester and provide estimates of microcephaly cases assuming different levels of risk as reported in empirical retrospective studies. Our approach represents a modeling effort aimed at understanding the potential magnitude and timing of the ZIKV epidemic and it can be potentially used as a template for the analysis of future mosquito-borne epidemics.

Real-Time Forecasting of the COVID-19 Outbreak in Chinese Provinces: Machine Learning Approach Using Novel Digital Data and Estimates From Mechanistic Models.

BACKGROUND: The inherent difficulty of identifying and monitoring emerging outbreaks caused by novel pathogens can lead to their rapid spread; and if left unchecked, they may become major public health threats to the planet. The ongoing coronavirus disease (COVID-19) outbreak, which has infected over 2,300,000 individuals and caused over 150,000 deaths, is an example of one of these catastrophic events. OBJECTIVE: We present a timely and novel methodology that combines disease estimates from mechanistic models and digital traces, via interpretable machine learning methodologies, to reliably forecast COVID-19 activity in Chinese provinces in real time. METHODS: Our method uses the following as inputs: (a) official health reports, (b) COVID-19-related internet search activity, (c) news media activity, and (d) daily forecasts of COVID-19 activity from a metapopulation mechanistic model. Our machine learning methodology uses a clustering technique that enables the exploitation of geospatial synchronicities of COVID-19 activity across Chinese provinces and a data augmentation technique to deal with the small number of historical disease observations characteristic of emerging outbreaks. RESULTS: Our model is able to produce stable and accurate forecasts 2 days ahead of the current time and outperforms a collection of baseline models in 27 out of 32 Chinese provinces. CONCLUSIONS: Our methodology could be easily extended to other geographies currently affected by COVID-19 to aid decision makers with monitoring and possibly prevention.

Correction: Real-Time Forecasting of the COVID-19 Outbreak in Chinese Provinces: Machine Learning Approach Using Novel Digital Data and Estimates From Mechanistic Models.

[This corrects the article DOI: 10.2196/20285.].

Quantifying the risk of local Zika virus transmission in the contiguous US during the 2015-2016 ZIKV epidemic.

BACKGROUND: Local mosquito-borne Zika virus (ZIKV) transmission has been reported in two counties in the contiguous United States (US), prompting the issuance of travel, prevention, and testing guidance across the contiguous US. Large uncertainty, however, surrounds the quantification of the actual risk of ZIKV introduction and autochthonous transmission across different areas of the US. METHODS: We present a framework for the projection of ZIKV autochthonous transmission in the contiguous US during the 2015-2016 epidemic using a data-driven stochastic and spatial epidemic model accounting for seasonal, environmental, and detailed population data. The model generates an ensemble of travel-related case counts and simulates their potential to have triggered local transmission at the individual level in the 2015-2016 ZIKV epidemic. RESULTS: We estimate the risk of ZIKV introduction and local transmission at the county level and at the 0.025° × 0.025° cell level across the contiguous US. We provide a risk measure based on the probability of observing local transmission in a specific location during a ZIKV epidemic modeled after the epidemic observed during the years 2015-2016. The high spatial and temporal resolution of the model allows us to generate statistical estimates of the number of ZIKV introductions leading to local transmission in each location. We find that the risk was spatially heterogeneously distributed and concentrated in a few specific areas that account for less than 1% of the contiguous US population. Locations in Texas and Florida that have actually experienced local ZIKV transmission were among the places at highest risk according to our results. We also provide an analysis of the key determinants for local transmission and identify the key introduction routes and their contributions to ZIKV transmission in the contiguous US. CONCLUSIONS: This framework provides quantitative risk estimates, fully captures the stochasticity of ZIKV introduction events, and is not biased by the under-ascertainment of cases due to asymptomatic cases. It provides general information on key risk determinants and data with potential uses in defining public health recommendations and guidance about ZIKV risk in the US.

A multiscale modeling framework for Scenario Modeling: Characterizing the heterogeneity of the COVID-19 epidemic in the US.

The Scenario Modeling Hub (SMH) initiative provides projections of potential epidemic scenarios in the United States (US) by using a multi-model approach. Our contribution to the SMH is generated by a multiscale model that combines the global epidemic metapopulation modeling approach (GLEAM) with a local epidemic and mobility model of the US (LEAM-US), first introduced here. The LEAM-US model consists of 3142 subpopulations each representing a single county across the 50 US states and the District of Columbia, enabling us to project state and national trajectories of COVID-19 cases, hospitalizations, and deaths under different epidemic scenarios. The model is age-structured, and multi-strain. It integrates data on vaccine administration, human mobility, and non-pharmaceutical interventions. The model contributed to all 17 rounds of the SMH, and allows for the mechanistic characterization of the spatio-temporal heterogeneities observed during the COVID-19 pandemic. Here we describe the mathematical and computational structure of our model, and present the results concerning the emergence of the SARS-CoV-2 Alpha variant (lineage designation B.1.1.7) as a case study. Our findings show considerable spatial and temporal heterogeneity in the introduction and diffusion of the Alpha variant, both at the level of individual states and combined statistical areas, as it competes against the ancestral lineage. We discuss the key factors driving the time required for the Alpha variant to rise to dominance within a population, and quantify the impact that the emergence of the Alpha variant had on the effective reproduction number at the state level. Overall, we show that our multiscale modeling approach is able to capture the complexity and heterogeneity of the COVID-19 pandemic response in the US.

Ensemble2: Scenarios ensembling for communication and performance analysis.

Throughout the COVID-19 pandemic, scenario modeling played a crucial role in shaping the decision-making process of public health policies. Unlike forecasts, scenario projections rely on specific assumptions about the future that consider different plausible states-of-the-world that may or may not be realized and that depend on policy interventions, unpredictable changes in the epidemic outlook, etc. As a consequence, long-term scenario projections require different evaluation criteria than the ones used for traditional short-term epidemic forecasts. Here, we propose a novel ensemble procedure for assessing pandemic scenario projections using the results of the Scenario Modeling Hub (SMH) for COVID-19 in the United States (US). By defining a "scenario ensemble" for each model and the ensemble of models, termed "Ensemble2", we provide a synthesis of potential epidemic outcomes, which we use to assess projections' performance, bypassing the identification of the most plausible scenario. We find that overall the Ensemble2 models are well-calibrated and provide better performance than the scenario ensemble of individual models. The ensemble procedure accounts for the full range of plausible outcomes and highlights the importance of scenario design and effective communication. The scenario ensembling approach can be extended to any scenario design strategy, with potential refinements including weighting scenarios and allowing the ensembling process to evolve over time.

The unequal effects of the health-economy trade-off during the COVID-19 pandemic.

Despite the global impact of the coronavirus disease 2019 pandemic, the question of whether mandated interventions have similar economic and public health effects as spontaneous behavioural change remains unresolved. Addressing this question, and understanding differential effects across socioeconomic groups, requires building quantitative and fine-grained mechanistic models. Here we introduce a data-driven, granular, agent-based model that simulates epidemic and economic outcomes across industries, occupations and income levels. We validate the model by reproducing key outcomes of the first wave of coronavirus disease 2019 in the New York metropolitan area. The key mechanism coupling the epidemic and economic modules is the reduction in consumption due to fear of infection. In counterfactual experiments, we show that a similar trade-off between epidemic and economic outcomes exists both when individuals change their behaviour due to fear of infection and when non-pharmaceutical interventions are imposed. Low-income workers, who perform in-person occupations in customer-facing industries, face the strongest trade-off.

Characterizing collective physical distancing in the U.S. during the first nine months of the COVID-19 pandemic.

The COVID-19 pandemic offers an unprecedented natural experiment providing insights into the emergence of collective behavioral changes of both exogenous (government mandated) and endogenous (spontaneous reaction to infection risks) origin. Here, we characterize collective physical distancing-mobility reductions, minimization of contacts, shortening of contact duration-in response to the COVID-19 pandemic in the pre-vaccine era by analyzing de-identified, privacy-preserving location data for a panel of over 5.5 million anonymized, opted-in U.S. devices. We define five indicators of users' mobility and proximity to investigate how the emerging collective behavior deviates from typical pre-pandemic patterns during the first nine months of the COVID-19 pandemic. We analyze both the dramatic changes due to the government mandated mitigation policies and the more spontaneous societal adaptation into a new (physically distanced) normal in the fall 2020. Using the indicators here defined we show that: a) during the COVID-19 pandemic, collective physical distancing displayed different phases and was heterogeneous across geographies, b) metropolitan areas displayed stronger reductions in mobility and contacts than rural areas; c) stronger reductions in commuting patterns are observed in geographical areas with a higher share of teleworkable jobs; d) commuting volumes during and after the lockdown period negatively correlate with unemployment rates; and e) increases in contact indicators correlate with future values of new deaths at a lag consistent with epidemiological parameters and surveillance reporting delays. In conclusion, this study demonstrates that the framework and indicators here presented can be used to analyze large-scale social distancing phenomena, paving the way for their use in future pandemics to analyze and monitor the effects of pandemic mitigation plans at the national and international levels.

Estimating the impact of COVID-19 vaccine inequities: a modeling study.

Access to COVID-19 vaccines on the global scale has been drastically hindered by structural socio-economic disparities. Here, we develop a data-driven, age-stratified epidemic model to evaluate the effects of COVID-19 vaccine inequities in twenty lower middle and low income countries (LMIC) selected from all WHO regions. We investigate and quantify the potential effects of higher or earlier doses availability. In doing so, we focus on the crucial initial months of vaccine distribution and administration, exploring counterfactual scenarios where we assume the same per capita daily vaccination rate reported in selected high income countries. We estimate that more than 50% of deaths (min-max range: [54-94%]) that occurred in the analyzed countries could have been averted. We further consider scenarios where LMIC had similarly early access to vaccine doses as high income countries. Even without increasing the number of doses, we estimate an important fraction of deaths (min-max range: [6-50%]) could have been averted. In the absence of the availability of high-income countries, the model suggests that additional non-pharmaceutical interventions inducing a considerable relative decrease of transmissibility (min-max range: [15-70%]) would have been required to offset the lack of vaccines. Overall, our results quantify the negative impacts of vaccine inequities and underscore the need for intensified global efforts devoted to provide faster access to vaccine programs in low and lower-middle-income countries.

Forecasting hospital-level COVID-19 admissions using real-time mobility data.

BACKGROUND: For each of the COVID-19 pandemic waves, hospitals have had to plan for deploying surge capacity and resources to manage large but transient increases in COVID-19 admissions. While a lot of effort has gone into predicting regional trends in COVID-19 cases and hospitalizations, there are far fewer successful tools for creating accurate hospital-level forecasts. METHODS: Large-scale, anonymized mobile phone data has been shown to correlate with regional case counts during the first two waves of the pandemic (spring 2020, and fall/winter 2021). Building off this success, we developed a multi-step, recursive forecasting model to predict individual hospital admissions; this model incorporates the following data: (i) hospital-level COVID-19 admissions, (ii) statewide test positivity data, and (iii) aggregate measures of large-scale human mobility, contact patterns, and commuting volume. RESULTS: Incorporating large-scale, aggregate mobility data as exogenous variables in prediction models allows us to make hospital-specific COVID-19 admission forecasts 21 days ahead. We show this through highly accurate predictions of hospital admissions for five hospitals in Massachusetts during the first year of the COVID-19 pandemic. CONCLUSIONS: The high predictive capability of the model was achieved by combining anonymized, aggregated mobile device data about users' contact patterns, commuting volume, and mobility range with COVID hospitalizations and test-positivity data. Mobility-informed forecasting models can increase the lead-time of accurate predictions for individual hospitals, giving managers valuable time to strategize how best to allocate resources to manage forthcoming surges.

During the COVID-19 pandemic, hospitals have needed to make challenging decisions around staffing and preparedness based on estimates of the number of admissions multiple weeks ahead. Forecasting techniques using methods from machine learning have been successfully applied to predict hospital admissions statewide, but the ability to accurately predict individual hospital admissions has proved elusive. Here, we incorporate details of the movement of people obtained from mobile phone data into a model that makes accurate predictions of the number of people who will be hospitalized 21 days ahead. This model will be useful for administrators and healthcare workers to plan staffing and discharge of patients to ensure adequate capacity to deal with forthcoming hospital admissions.

Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: A multi-model study.

Background: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5-11 years on COVID-19 burden and resilience against variant strains. Methods: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5-11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. Findings: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5-11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. Interpretation: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5-11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Funding: Various (see acknowledgments).

Informing pandemic response in the face of uncertainty. An evaluation of the U.S. COVID-19 Scenario Modeling Hub.

Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.

Potential impact of annual vaccination with reformulated COVID-19 vaccines: lessons from the U.S. COVID-19 Scenario Modeling Hub.

Importance: COVID-19 continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Objective: To project COVID-19 hospitalizations and deaths from April 2023-April 2025 under two plausible assumptions about immune escape (20% per year and 50% per year) and three possible CDC recommendations for the use of annually reformulated vaccines (no vaccine recommendation, vaccination for those aged 65+, vaccination for all eligible groups). Design: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023-April 15, 2025 under six scenarios representing the intersection of considered levels of immune escape and vaccination. State and national projections from eight modeling teams were ensembled to produce projections for each scenario. Setting: The entire United States. Participants: None. Exposure: Annually reformulated vaccines assumed to be 65% effective against strains circulating on June 15 of each year and to become available on September 1. Age and state specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. Main outcomes and measures: Ensemble estimates of weekly and cumulative COVID-19 hospitalizations and deaths. Expected relative and absolute reductions in hospitalizations and deaths due to vaccination over the projection period. Results: From April 15, 2023-April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November-January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% PI: 1,438,000-4,270,000) hospitalizations and 209,000 (90% PI: 139,000-461,000) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% CI: 104,000-355,000) fewer hospitalizations and 33,000 (95% CI: 12,000-54,000) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI: 29,000-69,000) fewer deaths. Conclusion and Relevance: COVID-19 is projected to be a significant public health threat over the coming two years. Broad vaccination has the potential to substantially reduce the burden of this disease.