Burden and characteristics of COVID-19 in the United States during 2020.

The COVID-19 pandemic disrupted health systems and economies throughout the world during 2020 and was particularly devastating for the United States, which experienced the highest numbers of reported cases and deaths during 20201-3. Many of the epidemiological features responsible for observed rates of morbidity and mortality have been reported4-8; however, the overall burden and characteristics of COVID-19 in the United States have not been comprehensively quantified. Here we use a data-driven model-inference approach to simulate the pandemic at county-scale in the United States during 2020 and estimate critical, time-varying epidemiological properties underpinning the dynamics of the virus. The pandemic in the United States during 2020 was characterized by national ascertainment rates that increased from 11.3% (95% credible interval (CI): 8.3-15.9%) in March to 24.5% (18.6-32.3%) during December. Population susceptibility at the end of the year was 69.0% (63.6-75.4%), indicating that about one third of the US population had been infected. Community infectious rates, the percentage of people harbouring a contagious infection, increased above 0.8% (0.6-1.0%) before the end of the year, and were as high as 2.4% in some major metropolitan areas. By contrast, the infection fatality rate fell to 0.3% by year's end.

Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

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.

A two-variant model of SARS-COV-2 transmission: estimating the characteristics of a newly emerging strain.

BACKGROUND: The Covid-19 pandemic has been characterized by the emergence of novel SARS-CoV-2 variants, each with distinct properties influencing transmission dynamics, immune escape, and virulence, which, in turn, influence their impact on local populations. Swift analysis of the properties of newly emerged variants is essential in the initial days and weeks to enhance readiness and facilitate the scaling of clinical and public health system responses. METHODS: This paper introduces a two-variant metapopulation compartmental model of disease transmission to simulate the dynamics of disease transmission during a period of transition to a newly dominant strain. Leveraging novel S-gene dropout analysis data and genomic sequencing data, combined with confirmed Covid-19 case data, we estimate the epidemiological characteristics of the Omicron variant, which replaced the Delta variant in late 2021 in Philadelphia, PA. We utilized a grid-search method to identify plausible combinations of model parameters, followed by an ensemble adjustment Kalman filter for parameter inference. RESULTS: The model successfully estimated key epidemiological parameters; we estimated the ascertainment rate of 0.22 (95% credible interval 0.15-0.29) and transmission rate of 5.0 (95% CI 2.4-6.6) for the Omicron variant. CONCLUSIONS: The study demonstrates the potential for this model-inference framework to provide real-time insights during the emergence of novel variants, aiding in timely public health responses.

A collaborative multiyear, multimodel assessment of seasonal influenza forecasting in the United States.

Influenza infects an estimated 9-35 million individuals each year in the United States and is a contributing cause for between 12,000 and 56,000 deaths annually. Seasonal outbreaks of influenza are common in temperate regions of the world, with highest incidence typically occurring in colder and drier months of the year. Real-time forecasts of influenza transmission can inform public health response to outbreaks. We present the results of a multiinstitution collaborative effort to standardize the collection and evaluation of forecasting models for influenza in the United States for the 2010/2011 through 2016/2017 influenza seasons. For these seven seasons, we assembled weekly real-time forecasts of seven targets of public health interest from 22 different models. We compared forecast accuracy of each model relative to a historical baseline seasonal average. Across all regions of the United States, over half of the models showed consistently better performance than the historical baseline when forecasting incidence of influenza-like illness 1 wk, 2 wk, and 3 wk ahead of available data and when forecasting the timing and magnitude of the seasonal peak. In some regions, delays in data reporting were strongly and negatively associated with forecast accuracy. More timely reporting and an improved overall accessibility to novel and traditional data sources are needed to improve forecasting accuracy and its integration with real-time public health decision making.

An open challenge to advance probabilistic forecasting for dengue epidemics.

A wide range of research has promised new tools for forecasting infectious disease dynamics, but little of that research is currently being applied in practice, because tools do not address key public health needs, do not produce probabilistic forecasts, have not been evaluated on external data, or do not provide sufficient forecast skill to be useful. We developed an open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem. Sixteen teams used a variety of methods and data to generate forecasts for 3 epidemiological targets (peak incidence, the week of the peak, and total incidence) over 8 dengue seasons in Iquitos, Peru and San Juan, Puerto Rico. Forecast skill was highly variable across teams and targets. While numerous forecasts showed high skill for midseason situational awareness, early season skill was low, and skill was generally lowest for high incidence seasons, those for which forecasts would be most valuable. A comparison of modeling approaches revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts. Leveraging these insights, data, and the forecasting framework will be critical to improve forecast skill and the application of forecasts in real time for epidemic preparedness and response. Moreover, key components of this project-integration with public health needs, a common forecasting framework, shared and standardized data, and open participation-can help advance infectious disease forecasting beyond dengue.

Accuracy of real-time multi-model ensemble forecasts for seasonal influenza in the U.S.

Seasonal influenza results in substantial annual morbidity and mortality in the United States and worldwide. Accurate forecasts of key features of influenza epidemics, such as the timing and severity of the peak incidence in a given season, can inform public health response to outbreaks. As part of ongoing efforts to incorporate data and advanced analytical methods into public health decision-making, the United States Centers for Disease Control and Prevention (CDC) has organized seasonal influenza forecasting challenges since the 2013/2014 season. In the 2017/2018 season, 22 teams participated. A subset of four teams created a research consortium called the FluSight Network in early 2017. During the 2017/2018 season they worked together to produce a collaborative multi-model ensemble that combined 21 separate component models into a single model using a machine learning technique called stacking. This approach creates a weighted average of predictive densities where the weight for each component is determined by maximizing overall ensemble accuracy over past seasons. In the 2017/2018 influenza season, one of the largest seasonal outbreaks in the last 15 years, this multi-model ensemble performed better on average than all individual component models and placed second overall in the CDC challenge. It also outperformed the baseline multi-model ensemble created by the CDC that took a simple average of all models submitted to the forecasting challenge. This project shows that collaborative efforts between research teams to develop ensemble forecasting approaches can bring measurable improvements in forecast accuracy and important reductions in the variability of performance from year to year. Efforts such as this, that emphasize real-time testing and evaluation of forecasting models and facilitate the close collaboration between public health officials and modeling researchers, are essential to improving our understanding of how best to use forecasts to improve public health response to seasonal and emerging epidemic threats.

Individual versus superensemble forecasts of seasonal influenza outbreaks in the United States.

Recent research has produced a number of methods for forecasting seasonal influenza outbreaks. However, differences among the predicted outcomes of competing forecast methods can limit their use in decision-making. Here, we present a method for reconciling these differences using Bayesian model averaging. We generated retrospective forecasts of peak timing, peak incidence, and total incidence for seasonal influenza outbreaks in 48 states and 95 cities using 21 distinct forecast methods, and combined these individual forecasts to create weighted-average superensemble forecasts. We compared the relative performance of these individual and superensemble forecast methods by geographic location, timing of forecast, and influenza season. We find that, overall, the superensemble forecasts are more accurate than any individual forecast method and less prone to producing a poor forecast. Furthermore, we find that these advantages increase when the superensemble weights are stratified according to the characteristics of the forecast or geographic location. These findings indicate that different competing influenza prediction systems can be combined into a single more accurate forecast product for operational delivery in real time.

Title evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2nd most accurate model measured by WIS in 2021-22 and the 5th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

The impact of COVID-19 vaccination in the US: Averted burden of SARS-COV-2-related cases, hospitalizations and deaths.

By August 1, 2022, the SARS-CoV-2 virus had caused over 90 million cases of COVID-19 and one million deaths in the United States. Since December 2020, SARS-CoV-2 vaccines have been a key component of US pandemic response; however, the impacts of vaccination are not easily quantified. Here, we use a dynamic county-scale metapopulation model to estimate the number of cases, hospitalizations, and deaths averted due to vaccination during the first six months of vaccine availability. We estimate that COVID-19 vaccination was associated with over 8 million fewer confirmed cases, over 120 thousand fewer deaths, and 700 thousand fewer hospitalizations during the first six months of the campaign.

Evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. Forecasting teams were asked to provide national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one through four weeks ahead for the 2021-22 and 2022-23 influenza seasons. Across both seasons, 26 teams submitted forecasts, with the submitting teams varying between seasons. Forecast skill was evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperformed the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble was the 2nd most accurate model measured by WIS in 2021-22 and the 5th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degraded over longer forecast horizons and during periods of rapid change. Current influenza forecasting efforts help inform situational awareness, but research is needed to address limitations, including decreased performance during periods of changing epidemic dynamics.

Early warnings of the potential for malaria transmission in rural Africa using the hydrology, entomology and malaria transmission simulator (HYDREMATS).

BACKGROUND: Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics. METHODS: HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future. RESULTS: Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone. CONCLUSIONS: HYDREMATS can be used to make reasonable predictions of mosquito populations and vectorial capacity, and provide early warnings of the potential for malaria epidemics in Africa.

A framework for evaluating the effects of observational type and quality on vector-borne disease forecast.

Recent research has advanced infectious disease forecasting from an aspiration to an operational reality. The accuracy of such operational forecasting depends on the quantity and quality of observations available for system optimization. In particular, for forecasting systems that use combined mechanistic model-inference approaches, a broad suite of epidemiological observations could be utilized, if these data were available in near real time. In cases where such data are limited, an in silica, synthetic framework for evaluating the potential benefits of observations on forecasting accuracy can allow researchers and public health officials to more optimally allocate resources for disease surveillance and monitoring. Here, we demonstrate the application of such a framework, using a model-inference system designed to predict dengue, and identify the type and quality of observations that would improve forecasting accuracy.

Compound Risks of Hurricane Evacuation Amid the COVID-19 Pandemic in the United States.

The 2020 Atlantic hurricane season was extremely active and included, as of early November, six hurricanes that made landfall in the United States during the global coronavirus disease 2019 (COVID-19) pandemic. Such an event would necessitate a large-scale evacuation, with implications for the trajectory of the pandemic. Here we model how a hypothetical hurricane evacuation from four counties in southeast Florida would affect COVID-19 case levels. We find that hurricane evacuation increases the total number of COVID-19 cases in both origin and destination locations; however, if transmission rates in destination counties can be kept from rising during evacuation, excess evacuation-induced case numbers can be minimized by directing evacuees to counties experiencing lower COVID-19 transmission rates. Ultimately, the number of excess COVID-19 cases produced by the evacuation depends on the ability of destination counties to meet evacuee needs while minimizing virus exposure through public health directives. These results are relevant to disease transmission during evacuations stemming from additional climate-related hazards such as wildfires and floods.

Superensemble forecasts of dengue outbreaks.

In recent years, a number of systems capable of predicting future infectious disease incidence have been developed. As more of these systems are operationalized, it is important that the forecasts generated by these different approaches be formally reconciled so that individual forecast error and bias are reduced. Here we present a first example of such multi-system, or superensemble, forecast. We develop three distinct systems for predicting dengue, which are applied retrospectively to forecast outbreak characteristics in San Juan, Puerto Rico. We then use Bayesian averaging methods to combine the predictions from these systems and create superensemble forecasts. We demonstrate that on average, the superensemble approach produces more accurate forecasts than those made from any of the individual forecasting systems.

Projected impacts of climate change on environmental suitability for malaria transmission in West Africa.

BACKGROUND: Climate change is expected to affect the distribution of environmental suitability for malaria transmission by altering temperature and rainfall patterns; however, the local and global impacts of climate change on malaria transmission are uncertain. OBJECTIVE: We assessed the effect of climate change on malaria transmission in West Africa. METHODS: We coupled a detailed mechanistic hydrology and entomology model with climate projections from general circulation models (GCMs) to predict changes in vectorial capacity, an indication of the risk of human malaria infections, resulting from changes in the availability of mosquito breeding sites and temperature-dependent development rates. Because there is strong disagreement in climate predictions from different GCMs, we focused on the GCM projections that produced the best and worst conditions for malaria transmission in each zone of the study area. RESULTS: Simulation-based estimates suggest that in the desert fringes of the Sahara, vectorial capacity would increase under the worst-case scenario, but not enough to sustain transmission. In the transitional zone of the Sahel, climate change is predicted to decrease vectorial capacity. In the wetter regions to the south, our estimates suggest an increase in vectorial capacity under all scenarios. However, because malaria is already highly endemic among human populations in these regions, we expect that changes in malaria incidence would be small. CONCLUSION: Our findings highlight the importance of rainfall in shaping the impact of climate change on malaria transmission in future climates. Even under the GCM predictions most conducive to malaria transmission, we do not expect to see a significant increase in malaria prevalence in this region.

Incorporating the effects of humidity in a mechanistic model of Anopheles gambiae mosquito population dynamics in the Sahel region of Africa.

BACKGROUND: Low levels of relative humidity are known to decrease the lifespan of mosquitoes. However, most current models of malaria transmission do not account for the effects of relative humidity on mosquito survival. In the Sahel, where relative humidity drops to levels <20% for several months of the year, we expect relative humidity to play a significant role in shaping the seasonal profile of mosquito populations. Here, we present a new formulation for Anopheles gambiae sensu lato (s.l.) mosquito survival as a function of temperature and relative humidity and investigate the effect of humidity on simulated mosquito populations. METHODS: Using existing observations on relationships between temperature, relative humidity and mosquito longevity, we developed a new equation for mosquito survival as a function of temperature and relative humidity. We collected simultaneous field observations on temperature, wind, relative humidity, and anopheline mosquito populations for two villages from the Sahel region of Africa, which are presented in this paper. We apply this equation to the environmental data and conduct numerical simulations of mosquito populations using the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS). RESULTS: Relative humidity drops to levels that are uncomfortable for mosquitoes at the end of the rainy season. In one village, Banizoumbou, water pools dried up and interrupted mosquito breeding shortly after the end of the rainy season. In this case, relative humidity had little effect on the mosquito population. However, in the other village, Zindarou, the relatively shallow water table led to water pools that persisted several months beyond the end of the rainy season. In this case, the decrease in mosquito survival due to relative humidity improved the model's ability to reproduce the seasonal pattern of observed mosquito abundance. CONCLUSIONS: We proposed a new equation to describe Anopheles gambiae s.l. mosquito survival as a function of temperature and relative humidity. We demonstrated that relative humidity can play a significant role in mosquito population and malaria transmission dynamics. Future modeling work should account for these effects of relative humidity.

Linking environmental variability to village-scale malaria transmission using a simple immunity model.

BACKGROUND: Individuals continuously exposed to malaria gradually acquire immunity that protects from severe disease and high levels of parasitization. Acquired immunity has been incorporated into numerous models of malaria transmission of varying levels of complexity (e.g. Bull World Health Organ 50:347, 1974; Am J Trop Med Hyg 75:19, 2006; Math Biosci 90:385-396, 1988). Most such models require prescribing inputs of mosquito biting rates or other entomological or epidemiological information. Here, we present a model with a novel structure that uses environmental controls of mosquito population dynamics to simulate the mosquito biting rates, malaria prevalence as well as variability in protective immunity of the population. METHODS: A simple model of acquired immunity to malaria is presented and tested within the framework of the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a coupled hydrology and agent-based entomology model. The combined model uses environmental data including rainfall, temperature, and topography to simulate malaria prevalence and level of acquired immunity in the human population. The model is used to demonstrate the effect of acquired immunity on malaria prevalence in two Niger villages that are hydrologically and entomologically very different. Simulations are conducted for the year 2006 and compared to malaria prevalence observations collected from the two villages. RESULTS: Blood smear samples from children show no clear difference in malaria prevalence between the two villages despite pronounced differences in observed mosquito abundance. The similarity in prevalence is attributed to the moderating effect of acquired immunity, which depends on prior exposure to the parasite through infectious bites - and thus the hydrologically determined mosquito abundance. Modelling the level of acquired immunity can affect village vulnerability to climatic anomalies. CONCLUSIONS: The model presented has a novel structure constituting a mechanistic link between spatial and temporal environmental variability and village-scale malaria transmission. Incorporating acquired immunity into the model has allowed simulation of prevalence in the two villages, and isolation of the effects of acquired immunity in dampening the difference in prevalence between the two villages. Without these effects, the difference in prevalence between the two villages would have been significantly larger in response to the large differences in mosquito populations and the associated biting rates.