Enhancing seasonal influenza projections: A mechanistic metapopulation model for long-term scenario planning.

In temperate regions, annual preparation by public health officials for seasonal influenza requires early-season long-term projections. These projections are different from short-term (e.g., 1-4 weeks ahead) forecasts that are typically updated weekly. Whereas short-term forecasts estimate what "will" likely happen in the near term, the goal of scenario projections is to guide long-term decision-making using "what if" scenarios. We developed a mechanistic metapopulation model and used it to provide long-term influenza projections to the Flu Scenario Modeling Hub. The scenarios differed in their assumptions about influenza vaccine effectiveness and prior immunity. The parameters of the model were inferred from early season hospitalization data and then simulated forward in time until June 3, 2023. We submitted two rounds of projections (mid-November and early December), with the second round being a repeat of the first with three more weeks of data (and consequently different model parameters). In this study, we describe the model, its calibration, and projections targets. The scenario projection outcomes for two rounds are compared with each other at state and national level reported daily hospitalizations. We show that although Rounds 2 and 3 were identical in definition, the addition of three weeks of data produced an improvement to model fits. These changes resulted in earlier projections for peak incidence, lower projections for peak magnitude and relatively small changes to cumulative projections. In both rounds, all four scenarios presented conceivable outcomes, with some scenarios agreeing well with observations. We discuss how to interpret this agreement, emphasizing that this does not imply that one scenario or another provides the ground truth. Our model's performance suggests that its underlying assumptions provided plausible bounds for what could happen during an influenza season following two seasons of low circulation. We suggest that such projections would provide actionable estimates for public health officials.

COVID-19: On the Disparity in Outcomes Between Military and Civilian Populations.

INTRODUCTION: The CoronaVirus Disease 2019 (COVID-19) pandemic remains a formidable threat to populations around the world. The U.S. Military, in particular, represents a unique and distinguishable subset of the population, primarily due to the age and gender of active duty personnel. Current investigations have focused on health outcome forecasts for civilian populations, making them of limited value for military planning. MATERIALS AND METHODS: We have developed and applied an age-structured susceptible, exposed, infectious, recovered, or dead compartmental model for both civilian and military populations, driven by estimates of the time-dependent reproduction number, R(t), which can be both fit to available data and also forecast future cases, intensive care unit (ICU) patients, and deaths. RESULTS: We show that the expected health outcomes for active duty military populations are substantially different than for civilian populations of the same size. Specifically, while the number of cases is not expected to differ dramatically, severity, both in terms of ICU burdens and deaths, is substantially lower. CONCLUSIONS: Our results confirm that the burden placed on military health centers will be substantially lower than that for equivalent-sized civilian populations. More practically, the tool we have developed to investigate this (https://q.predsci.com/covid19/) can be used by military health planners to estimate the resources needed in particular locations based on current estimates of the transmission profiles of COVID-19 within the surrounding civilian population in which the military installation is embedded. As this tool continues to be developed, it can be used to assess the likely impact of different intervention strategies, as well as vaccine policies; both for the current pandemic as well as future ones.

Consistent pattern of epidemic slowing across many geographies led to longer, flatter initial waves of the COVID-19 pandemic.

To define appropriate planning scenarios for future pandemics of respiratory pathogens, it is important to understand the initial transmission dynamics of COVID-19 during 2020. Here, we fit an age-stratified compartmental model with a flexible underlying transmission term to daily COVID-19 death data from states in the contiguous U.S. and to national and sub-national data from around the world. The daily death data of the first months of the COVID-19 pandemic was qualitatively categorized into one of four main profile types: "spring single-peak", "summer single-peak", "spring/summer two-peak" and "broad with shoulder". We estimated a reproduction number R as a function of calendar time tc and as a function of time since the first death reported in that population (local pandemic time, tp). Contrary to the diversity of categories and range of magnitudes in death incidence profiles, the R(tp) profiles were much more homogeneous. We found that in both the contiguous U.S. and globally, the initial value of both R(tc) and R(tp) was substantial: at or above two. However, during the early months, pandemic time R(tp) decreased exponentially to a value that hovered around one. This decrease was accompanied by a reduction in the variance of R(tp). For calendar time R(tc), the decrease in magnitude was slower and non-exponential, with a smaller reduction in variance. Intriguingly, similar trends of exponential decrease and reduced variance were not observed in raw death data. Our findings suggest that the combination of specific government responses and spontaneous changes in behaviour ensured that transmissibility dropped, rather than remaining constant, during the initial phases of a pandemic. Future pandemic planning scenarios should include models that assume similar decreases in transmissibility, which lead to longer epidemics with lower peaks when compared with models based on constant transmissibility.

COVID-19 deaths: Which explanatory variables matter the most?

More than a year since the appearance of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), many questions about the disease COVID-19 have been answered; however, many more remain poorly understood. Although the situation continues to evolve, it is crucial to understand what factors may be driving transmission through different populations, both for potential future waves, as well as the implications for future pandemics. In this report, we compiled a database of more than 28 potentially explanatory variables for each of the 50 U.S. states through early May 2020. Using a combination of traditional statistical and modern machine learning approaches, we identified those variables that were the most statistically significant, and, those that were the most important. These variables were chosen to be fiduciaries of a range of possible drivers for COVID-19 deaths in the USA. We found that population-weighted population density (PWPD), some "stay at home" metrics, monthly temperature and precipitation, race/ethnicity, and chronic low-respiratory death rate, were all statistically significant. Of these, PWPD and mobility metrics dominated. This suggests that the biggest impact on COVID-19 deaths was, at least initially, a function of where you lived, and not what you did. However, clearly, increasing social distancing has the net effect of (at least temporarily) reducing the effective PWPD. Our results strongly support the idea that the loosening of "lock-down" orders should be tailored to the local PWPD. In contrast to these variables, while still statistically significant, race/ethnicity, health, and climate effects could only account for a few percent of the variability in deaths. Where associations were anticipated but were not found, we discuss how limitations in the parameters chosen may mask a contribution that might otherwise be present.

Accurate influenza forecasts using type-specific incidence data for small geographic units.

Influenza incidence forecasting is used to facilitate better health system planning and could potentially be used to allow at-risk individuals to modify their behavior during a severe seasonal influenza epidemic or a novel respiratory pandemic. For example, the US Centers for Disease Control and Prevention (CDC) runs an annual competition to forecast influenza-like illness (ILI) at the regional and national levels in the US, based on a standard discretized incidence scale. Here, we use a suite of forecasting models to analyze type-specific incidence at the smaller spatial scale of clusters of nearby counties. We used data from point-of-care (POC) diagnostic machines over three seasons, in 10 clusters, capturing: 57 counties; 1,061,891 total specimens; and 173,909 specimens positive for Influenza A. Total specimens were closely correlated with comparable CDC ILI data. Mechanistic models were substantially more accurate when forecasting influenza A positive POC data than total specimen POC data, especially at longer lead times. Also, models that fit subpopulations of the cluster (individual counties) separately were better able to forecast clusters than were models that directly fit to aggregated cluster data. Public health authorities may wish to consider developing forecasting pipelines for type-specific POC data in addition to ILI data. Simple mechanistic models will likely improve forecast accuracy when applied at small spatial scales to pathogen-specific data before being scaled to larger geographical units and broader syndromic data. Highly local forecasts may enable new public health messaging to encourage at-risk individuals to temporarily reduce their social mixing during seasonal peaks and guide public health intervention policy during potentially severe novel influenza pandemics.

Forecasting national and regional influenza-like illness for the USA.

Health planners use forecasts of key metrics associated with influenza-like illness (ILI); near-term weekly incidence, week of season onset, week of peak, and intensity of peak. Here, we describe our participation in a weekly prospective ILI forecasting challenge for the United States for the 2016-17 season and subsequent evaluation of our performance. We implemented a metapopulation model framework with 32 model variants. Variants differed from each other in their assumptions about: the force-of-infection (FOI); use of uninformative priors; the use of discounted historical data for not-yet-observed time points; and the treatment of regions as either independent or coupled. Individual model variants were chosen subjectively as the basis for our weekly forecasts; however, a subset of coupled models were only available part way through the season. Most frequently, during the 2016-17 season, we chose; FOI variants with both school vacations and humidity terms; uninformative priors; the inclusion of discounted historical data for not-yet-observed time points; and coupled regions (when available). Our near-term weekly forecasts substantially over-estimated incidence early in the season when coupled models were not available. However, our forecast accuracy improved in absolute terms and relative to other teams once coupled solutions were available. In retrospective analysis, we found that the 2016-17 season was not typical: on average, coupled models performed better when fit without historically augmented data. Also, we tested a simple ensemble model for the 2016-17 season and found that it underperformed our subjective choice for all forecast targets. In this study, we were able to improve accuracy during a prospective forecasting exercise by coupling dynamics between regions. Although reduction of forecast subjectivity should be a long-term goal, some degree of human intervention is likely to improve forecast accuracy in the medium-term in parallel with the systematic consideration of more sophisticated ensemble approaches.