An Evaluation of Prospective COVID-19 Modeling: From Data to Science Translation

BackgroundInfectious disease modeling can serve as a powerful tool for science-based management of outbreaks, providing situational awareness and decision support for policy makers. Predictive modeling of an emerging disease is challenging due to limited knowledge on its epidemiological characteristics. For COVID-19, the prediction difficulty was further compounded by continuously changing policies, varying behavioral responses, poor availability and quality of crucial datasets, and the variable influence of different factors as the pandemic progresses. Due to these challenges, predictive modeling for COVID-19 has earned a mixed track record. MethodsWe provide a systematic review of prospective, data-driven modeling studies on population-level dynamics of COVID-19 in the US and conduct a quantitative assessment on crucial elements of modeling, with a focus on the aspects of modeling that are critical to make them useful for decision-makers. For each study, we documented the forecasting window, methodology, prediction target, datasets used, geographic resolution, whether they expressed quantitative uncertainty, the type of performance evaluation, and stated limitations. We present statistics for each category and discuss their distribution across the set of studies considered. We also address differences in these model features based on fields of study. FindingsOur initial search yielded 2,420 papers, of which 119 published papers and 17 preprints were included after screening. The most common datasets relied upon for COVID-19 modeling were counts of cases (93%) and deaths (62%), followed by mobility (26%), demographics (25%), hospitalizations (12%), and policy (12%). Our set of papers contained a roughly equal number of short-term (46%) and long-term (60%) predictions (defined as a prediction horizon longer than 4 weeks) and statistical (43%) versus compartmental (47%) methodologies. The target variables used were predominantly cases (89%), deaths (52%), hospitalizations (10%), and Rt (9%). We found that half of the papers in our analysis did not express quantitative uncertainty (50%). Among short-term prediction models, which can be fairly evaluated against truth data, 25% did not conduct any performance evaluation, and most papers were not evaluated over a timespan that includes varying epidemiological dynamics. The main categories of limitations stated by authors were disregarded factors (39%), data quality (28%), unknowable factors (26%), limitations specific to the methods used (22%), data availability (16%), and limited generalizability (8%). 36% of papers did not list any limitations in their discussion or conclusion section. InterpretationPublished COVID-19 models were found to be consistently lacking in some of the most important elements required for usability and translation, namely transparency, expressing uncertainty, performance evaluation, stating limitations, and communicating appropriate interpretations. Adopting the EPIFORGE 2020 guidelines would address these shortcomings and improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. We also discovered that most of the operational models that have been used in real-time to inform decision-making have not yet made it into the published literature, which highlights that the current publication system is not suited to the rapid information-sharing needs of outbreaks. Furthermore, data quality was identified to be one of the most important drivers of model performance, and a consistent limitation noted by the modeling community. The US public health infrastructure was not equipped to provide timely, high-quality COVID-19 data, which is required for effective modeling. Thus, a systematic infrastructure for improved data collection and sharing should be a major area of investment to support future pandemic preparedness.

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

BackgroundSARS-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. MethodsNine 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. FindingsAbsent 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. ConclusionsResults 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.

Sample Size Calculations for Variant Surveillance in the Presence of Biological and Systematic Biases

As demonstrated during the SARS-CoV-2 pandemic, detecting and tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. Pathogen genome sequencing has emerged as the primary tool for variant characterization, so it is important to consider the number of sequences needed when designing surveillance programs or studies, both to ensure accurate conclusions and to optimize use of limited resources. However, current approaches to calculating sample size for variant monitoring often do not account for the biological and logistical processes that can bias which infections are detected and which samples are ultimately selected for sequencing. In this manuscript, we introduce a framework that models the full process-- including potential sources of bias--from infection detection to variant characterization, and we demonstrate how to use this framework to calculate appropriate sample sizes for sequencing-based surveillance studies. We consider both cross-sectional and continuous sampling, and we have implemented our method in a publicly available tool that allows users to estimate necessary sample sizes given a specific aim (e.g., variant detection or measuring variant prevalence) and sampling method. Our framework is designed to be easy to use, while also flexible enough to be adapted to other pathogens and surveillance scenarios.

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.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multi-model ensemble forecast that combined predictions from dozens of different research groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naive baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-week horizon 3-5 times larger than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks. Significance StatementThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the US. Results show high variation in accuracy between and within stand-alone models, and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public health action.

Testing out of quarantine

Since SARS-CoV-2 emerged, a 14-day quarantine has been recommended based on COVID-19"s incubation period. Using an RT-PCR or rapid antigen test to "test out" of quarantine is a frequently proposed strategy to shorten duration without increasing risk. We calculated the probability that infected individuals test negative for SARS-CoV-2 on a particular day post-infection and remain symptom free for some period of time. We estimate that an infected individual has a 20.1% chance (95% CI 9.8-32.6) of testing RT-PCR negative on day five post-infection and remaining asymptomatic until day seven. We also show that the added information a test provides decreases as we move further from the test date, hence a less sensitive test that returns rapid results is often preferable to a more sensitive test with a delay.

Effect of specific non-pharmaceutical intervention policies on SARS-CoV-2 transmission in the counties of the United States

Non-pharmaceutical interventions (NPIs) remain the only widely available tool for controlling the ongoing SARS-CoV-2 pandemic. We estimated weekly values of the effective basic reproductive number (Reff) using a mechanistic metapopulation model and associated these with county-level characteristics and NPIs in the United States (US). Interventions that included school and leisure activities closure and nursing home visiting bans were all associated with an Reff below 1 when combined with either stay at home orders (median Reff 0.97, 95% confidence interval (CI) 0.58-1.39)* or face masks (median Reff 0.97, 95% CI 0.58-1.39)*. While direct causal effects of interventions remain unclear, our results suggest that relaxation of some NPIs will need to be counterbalanced by continuation and/or implementation of others.

Maximizing and evaluating the impact of test-trace-isolate programs

September 2, 2020 BackgroundTest-trace-isolate programs are an essential part of COVID-19 control that offer a more targeted approach than many other non-pharmaceutical interventions. Effective use of such programs requires methods to estimate their current and anticipated impact. Methods and FindingsWe present a mathematical modeling framework to evaluate the expected reductions in the reproductive number, R, from test-trace-isolate programs. This framework is implemented in a publicly available R package and an online application. We evaluated the effects of case detection, speed of isolation, contact tracing completeness and speed of quarantine using parameters consistent with COVID-19 transmission (R0 = 2.5, generation time 6.5 days). We show that R is most sensitive to changes to the proportion of infections detected in almost all scenarios, and other metrics have a reduced impact when case detection levels are low (< 30%). Although test-trace-isolate programs can contribute substantially to reducing R, exceptional performance across all metrics is needed to bring R below one through test-trace-isolate alone, highlighting the need for comprehensive control strategies. Formally framing the dynamical process also indicates that metrics used to evaluate performance of test-trace-isolate, such as the proportion of identified infections among traced contacts, may be misleading. While estimates of program performance are sensitive to assumptions about COVID-19 natural history, our qualitative findings are robust across numerous sensitivity analyses. ConclusionsEffective test-trace-isolate programs first need to be strong in the "test" component, as case detection underlies all other program activities. Even moderately effective test-trace-isolate programs are an important tool for controlling the COVID-19 pandemic, and can alleviate the need for more restrictive social distancing measures.

Ensemble Forecasts of Coronavirus Disease 2019 (COVID-19) in the U.S.

BackgroundThe COVID-19 pandemic has driven demand for forecasts to guide policy and planning. Previous research has suggested that combining forecasts from multiple models into a single "ensemble" forecast can increase the robustness of forecasts. Here we evaluate the real-time application of an open, collaborative ensemble to forecast deaths attributable to COVID-19 in the U.S. MethodsBeginning on April 13, 2020, we collected and combined one- to four-week ahead forecasts of cumulative deaths for U.S. jurisdictions in standardized, probabilistic formats to generate real-time, publicly available ensemble forecasts. We evaluated the point prediction accuracy and calibration of these forecasts compared to reported deaths. ResultsAnalysis of 2,512 ensemble forecasts made April 27 to July 20 with outcomes observed in the weeks ending May 23 through July 25, 2020 revealed precise short-term forecasts, with accuracy deteriorating at longer prediction horizons of up to four weeks. At all prediction horizons, the prediction intervals were well calibrated with 92-96% of observations falling within the rounded 95% prediction intervals. ConclusionsThis analysis demonstrates that real-time, publicly available ensemble forecasts issued in April-July 2020 provided robust short-term predictions of reported COVID-19 deaths in the United States. With the ongoing need for forecasts of impacts and resource needs for the COVID-19 response, the results underscore the importance of combining multiple probabilistic models and assessing forecast skill at different prediction horizons. Careful development, assessment, and communication of ensemble forecasts can provide reliable insight to public health decision makers.

A scenario modeling pipeline for COVID-19 emergency planning

Coronavirus disease 2019 (COVID-19) has caused strain on health systems worldwide due to its high mortality rate and the large portion of cases requiring critical care and mechanical ventilation. During these uncertain times, public health decision makers, from city health departments to federal agencies, sought the use of epidemiological models for decision support in allocating resources, developing non-pharmaceutical interventions, and characterizing the dynamics of COVID-19 in their jurisdictions. In response, we developed a flexible scenario modeling pipeline that could quickly tailor models for decision makers seeking to compare projections of epidemic trajectories and healthcare impacts from multiple intervention scenarios in different locations. Here, we present the components and configurable features of the COVID Scenario Pipeline, with a vignette detailing its current use. We also present model limitations and active areas of development to meet ever-changing decision maker needs.