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.

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.

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).

Data-driven scalable pipeline using national agent-based models for real-time pandemic response and decision support.

This paper describes an integrated, data-driven operational pipeline based on national agent-based models to support federal and state-level pandemic planning and response. The pipeline consists of (i) an automatic semantic-aware scheduling method that coordinates jobs across two separate high performance computing systems; (ii) a data pipeline to collect, integrate and organize national and county-level disaggregated data for initialization and post-simulation analysis; (iii) a digital twin of national social contact networks made up of 288 Million individuals and 12.6 Billion time-varying interactions covering the US states and DC; (iv) an extension of a parallel agent-based simulation model to study epidemic dynamics and associated interventions. This pipeline can run 400 replicates of national runs in less than 33 h, and reduces the need for human intervention, resulting in faster turnaround times and higher reliability and accuracy of the results. Scientifically, the work has led to significant advances in real-time epidemic sciences.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.

In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July-December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July-December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July-December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.

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: SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods: Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings: Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in 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 where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions: Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.

Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July-December 2021. WHAT IS ADDED BY THIS REPORT?: Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July-December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen.

Scalable Epidemiological Workflows to Support COVID-19 Planning and Response.

The COVID-19 global outbreak represents the most significant epidemic event since the 1918 influenza pandemic. Simulations have played a crucial role in supporting COVID-19 planning and response efforts. Developing scalable workflows to provide policymakers quick responses to important questions pertaining to logistics, resource allocation, epidemic forecasts and intervention analysis remains a challenging computational problem. In this work, we present scalable high performance computing-enabled workflows for COVID-19 pandemic planning and response. The scalability of our methodology allows us to run fine-grained simulations daily, and to generate county-level forecasts and other counter-factual analysis for each of the 50 states (and DC), 3140 counties across the USA. Our workflows use a hybrid cloud/cluster system utilizing a combination of local and remote cluster computing facilities, and using over 20,000 CPU cores running for 6-9 hours every day to meet this objective. Our state (Virginia), state hospital network, our university, the DOD and the CDC use our models to guide their COVID-19 planning and response efforts. We began executing these pipelines March 25, 2020, and have delivered and briefed weekly updates to these stakeholders for over 30 weeks without interruption.

Prioritizing allocation of COVID-19 vaccines based on social contacts increases vaccination effectiveness.

We study allocation of COVID-19 vaccines to individuals based on the structural properties of their underlying social contact network. Even optimistic estimates suggest that most countries will likely take 6 to 24 months to vaccinate their citizens. These time estimates and the emergence of new viral strains urge us to find quick and effective ways to allocate the vaccines and contain the pandemic. While current approaches use combinations of age-based and occupation-based prioritizations, our strategy marks a departure from such largely aggregate vaccine allocation strategies. We propose a novel approach motivated by recent advances in (i) science of real-world networks that point to efficacy of certain vaccination strategies and (ii) digital technologies that improve our ability to estimate some of these structural properties. Using a realistic representation of a social contact network for the Commonwealth of Virginia, combined with accurate surveillance data on spatiotemporal cases and currently accepted models of within- and between-host disease dynamics, we study how a limited number of vaccine doses can be strategically distributed to individuals to reduce the overall burden of the pandemic. We show that allocation of vaccines based on individuals' degree (number of social contacts) and total social proximity time is significantly more effective than the currently used age-based allocation strategy in terms of number of infections, hospitalizations and deaths. Our results suggest that in just two months, by March 31, 2021, compared to age-based allocation, the proposed degree-based strategy can result in reducing an additional 56-110k infections, 3.2- 5.4k hospitalizations, and 700-900 deaths just in the Commonwealth of Virginia. Extrapolating these results for the entire US, this strategy can lead to 3-6 million fewer infections, 181-306k fewer hospitalizations, and 51-62k fewer deaths compared to age-based allocation. The overall strategy is robust even: (i) if the social contacts are not estimated correctly; (ii) if the vaccine efficacy is lower than expected or only a single dose is given; (iii) if there is a delay in vaccine production and deployment; and (iv) whether or not non-pharmaceutical interventions continue as vaccines are deployed. For reasons of implementability, we have used degree, which is a simple structural measure and can be easily estimated using several methods, including the digital technology available today. These results are significant, especially for resource-poor countries, where vaccines are less available, have lower efficacy, and are more slowly distributed.

From 5Vs to 6Cs: Operationalizing Epidemic Data Management with COVID-19 Surveillance.

The COVID-19 pandemic brought to the forefront an unprecedented need for experts, as well as citizens, to visualize spatio-temporal disease surveillance data. Web application dashboards were quickly developed to fill this gap, including those built by JHU, WHO, and CDC, but all of these dashboards supported a particular niche view of the pandemic (ie, current status or specific regions). In this paper, we describe our work developing our own COVID-19 Surveillance Dashboard, available at https://nssac.bii.virginia.edu/covid-19/dashboard/, which offers a universal view of the pandemic while also allowing users to focus on the details that interest them. From the beginning, our goal was to provide a simple visual way to compare, organize, and track near-real-time surveillance data as the pandemic progresses. Our dashboard includes a number of advanced features for zooming, filtering, categorizing and visualizing multiple time series on a single canvas. In developing this dashboard, we have also identified 6 key metrics we call the 6Cs standard which we propose as a standard for the design and evaluation of real-time epidemic science dashboards. Our dashboard was one of the first released to the public, and remains one of the most visited and highly used. Our group uses it to support federal, state and local public health authorities, and it is used by people worldwide to track the pandemic evolution, build their own dashboards, and support their organizations as they plan their responses to the pandemic. We illustrate the utility of our dashboard by describing how it can be used to support data story-telling - an important emerging area in data science.

An Automated Approach for Finding Spatio-Temporal Patterns of Seasonal Influenza in the United States: Algorithm Validation Study.

BACKGROUND: Agencies such as the Centers for Disease Control and Prevention (CDC) currently release influenza-like illness incidence data, along with descriptive summaries of simple spatio-temporal patterns and trends. However, public health researchers, government agencies, as well as the general public, are often interested in deeper patterns and insights into how the disease is spreading, with additional context. Analysis by domain experts is needed for deriving such insights from incidence data. OBJECTIVE: Our goal was to develop an automated approach for finding interesting spatio-temporal patterns in the spread of a disease over a large region, such as regions which have specific characteristics (eg, high incidence in a particular week, those which showed a sudden change in incidence) or regions which have significantly different incidence compared to earlier seasons. METHODS: We developed techniques from the area of transactional data mining for characterizing and finding interesting spatio-temporal patterns in disease spread in an automated manner. A key part of our approach involved using the principle of minimum description length for representing a given target set in terms of combinations of attributes (referred to as clauses); we considered both positive and negative clauses, relaxed descriptions which approximately represent the set, and used integer programming to find such descriptions. Finally, we designed an automated approach, which examines a large space of sets corresponding to different spatio-temporal patterns, and ranks them based on the ratio of their size to their description length (referred to as the compression ratio). RESULTS: We applied our methods using minimum description length to find spatio-temporal patterns in the spread of seasonal influenza in the United States using state level influenza-like illness activity indicator data from the CDC. We observed that the compression ratios were over 2.5 for 50% of the chosen sets, when approximate descriptions and negative clauses were allowed. Sets with high compression ratios (eg, over 2.5) corresponded to interesting patterns in the spatio-temporal dynamics of influenza-like illness. Our approach also outperformed description by solution in terms of the compression ratio. CONCLUSIONS: Our approach, which is an unsupervised machine learning method, can provide new insights into patterns and trends in the disease spread in an automated manner. Our results show that the description complexity is an effective approach for characterizing sets of interest, which can be easily extended to other diseases and regions beyond influenza in the US. Our approach can also be easily adapted for automated generation of narratives.