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BackgroundCoronavirus 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 findingsThe 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. ConclusionsCOVID-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. 

Individual models of infectious diseases or trajectories coming from different simulations may vary considerably, making it challenging for public communication and supporting policy-making. Therefore, it is common in public health to first create a consensus across multiple models and simulations through ensembling. However, current methods are limited to mean and median ensembles that perform aggregation of scale (cases, hospitalizations, deaths) along the time axis, which often misrepresents the underlying trajectories -- e.g., they underrepresent the peak. Instead, we wish to create an ensemble that represents aggregation simultaneously over both time and scale and thus better preserves the properties of the trajectories. This is particularly useful for public health where time-series have a sequence of meaningful local trends that are ordered, e.g., a surge to an increase to a peak to a decrease. We propose a novel alignment method DTW+SBA, which combines a representation of local trends along with dynamic time warping barycenter averaging. We prove key properties of this method that ensure appropriate alignment based on local trends. We demonstrate on real multi-model outputs that our approach preserves the properties of underlying trajectories. We also show that our alignment leads to a more sensible clustering of epidemic trajectories. 

During the COVID-19 pandemic, a major driver of new surges has been the emergence of new variants. When a new variant emerges in one or more countries, other nations monitor its spread in preparation for its potential arrival. The impact of the new variant and the timings of epidemic peaks in a country highly depend on when the variant arrives. The current methods for predicting the spread of new variants rely on statistical modeling, however, these methods work only when the new variant has already arrived in the region of interest and has a significant prevalence. Can we predict when a variant existing elsewhere will arrive in a given region? To address this question, we propose a variant-dynamics-informed Graph Neural Network (GNN) approach. First, we derive the dynamics of variant prevalence across pairs of regions (countries) that apply to a large class of epidemic models. The dynamics motivate the introduction of certain features in the GNN. We demonstrate that our proposed dynamics-informed GNN outperforms all the baselines, including the currently pervasive framework of Physics-Informed Neural Networks (PINNs). To advance research in this area, we introduce a benchmarking tool to assess a user-defined model's prediction performance across 87 countries and 36 variants. 

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1–4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.