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  1. Abstract Background

    Dynamical mathematical models defined by a system of differential equations are typically not easily accessible to non-experts. However, forecasts based on these types of models can help gain insights into the mechanisms driving the process and may outcompete simpler phenomenological growth models. Here we introduce a friendly toolbox,SpatialWavePredict, to characterize and forecast the spatial wave sub-epidemic model, which captures diverse wave dynamics by aggregating multiple asynchronous growth processes and has outperformed simpler phenomenological growth models in short-term forecasts of various infectious diseases outbreaks including SARS, Ebola, and the early waves of the COVID-19 pandemic in the US.

    Results

    This tutorial-based primer introduces and illustrates a user-friendly MATLAB toolbox for fitting and forecasting time-series trajectories using an ensemble spatial wave sub-epidemic model based on ordinary differential equations. Scientists, policymakers, and students can use the toolbox to conduct real-time short-term forecasts. The five-parameter epidemic wave model in the toolbox aggregates linked overlapping sub-epidemics and captures a rich spectrum of epidemic wave dynamics, including oscillatory wave behavior and plateaus. An ensemble strategy aims to improve forecasting performance by combining the resulting top-ranked models. The toolbox provides a tutorial for forecasting time-series trajectories, including the full uncertainty distribution derived through parametric bootstrapping, which is needed to construct prediction intervals and evaluate their accuracy. Functions are available to assess forecasting performance, estimation methods, error structures in the data, and forecasting horizons. The toolbox also includes functions to quantify forecasting performance using metrics that evaluate point and distributional forecasts, including the weighted interval score.

    Conclusions

    We have developed the first comprehensive toolbox to characterize and forecast time-series data using an ensemble spatial wave sub-epidemic wave model. As an epidemic situation or contagion occurs, the tools presented in this tutorial can facilitate policymakers to guide the implementation of containment strategies and assess the impact of control interventions. We demonstrate the functionality of the toolbox with examples, including a tutorial video, and is illustrated using daily data on the COVID-19 pandemic in the USA.

     
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  2. Abstract

    The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data.

     
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  3. Mathematical models based on systems of ordinary differential equations (ODEs) are frequently applied in various scientific fields to assess hypotheses, estimate key model parameters, and generate predictions about the system's state. To support their application, we present a comprehensive, easy‐to‐use, and flexible MATLAB toolbox,QuantDiffForecast, and associated tutorial to estimate parameters and generate short‐term forecasts with quantified uncertainty from dynamical models based on systems of ODEs. We provide software (https://github.com/gchowell/paramEstimation_forecasting_ODEmodels/) and detailed guidance on estimating parameters and forecasting time‐series trajectories that are characterized using ODEs with quantified uncertainty through a parametric bootstrapping approach. It includes functions that allow the user to infer model parameters and assess forecasting performance for different ODE models specified by the user, using different estimation methods and error structures in the data. The tutorial is intended for a diverse audience, including students training in dynamic systems, and will be broadly applicable to estimate parameters and generate forecasts from models based on ODEs. The functions included in the toolbox are illustrated using epidemic models with varying levels of complexity applied to data from the 1918 influenza pandemic in San Francisco. A tutorial video that demonstrates the functionality of the toolbox is included.

     
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  4. Abstract

    In this work, the COVID-19 pandemic burden in Ukraine is investigated retrospectively using the excess mortality measures during 2020–2021. In particular, the epidemic impact on the Ukrainian population is studied via the standardized both all-cause and cause-specific mortality scores before and during the epidemic. The excess mortality counts during the pandemic were predicted based on historic data using parametric and nonparametric modeling and then compared with the actual reported counts to quantify the excess. The corresponding standardized mortalityP-score metrics were also compared with the neighboring countries. In summary, there were three “waves” of excess all-cause mortality in Ukraine in December 2020, April 2021 and November 2021 with excess of 32%, 43% and 83% above the expected mortality. Each new “wave” of the all-cause mortality was higher than the previous one and the mortality “peaks” corresponded in time to three “waves” of lab-confirmed COVID-19 mortality. The lab-confirmed COVID-19 mortality constituted 9% to 24% of the all-cause mortality during those three peak months. Overall, the mortality trends in Ukraine over time were similar to neighboring countries where vaccination coverage was similar to that in Ukraine. For cause-specific mortality, the excess observed was due to pneumonia as well as circulatory system disease categories that peaked at the same times as the all-cause and lab-confirmed COVID-19 mortality, which was expected. The pneumonias as well as circulatory system disease categories constituted the majority of all cases during those peak times. The seasonality in mortality due to the infectious and parasitic disease category became less pronounced during the pandemic. While the reported numbers were always relatively low, alcohol-related mortality also declined during the pandemic.

     
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  5. Abstract Background

    Beginning May 7, 2022, multiple nations reported an unprecedented surge in monkeypox cases. Unlike past outbreaks, differences in affected populations, transmission mode, and clinical characteristics have been noted. With the existing uncertainties of the outbreak, real-time short-term forecasting can guide and evaluate the effectiveness of public health measures.

    Methods

    We obtained publicly available data on confirmed weekly cases of monkeypox at the global level and for seven countries (with the highest burden of disease at the time this study was initiated) from the Our World in Data (OWID) GitHub repository and CDC website. We generated short-term forecasts of new cases of monkeypox across the study areas using an ensemble n-sub-epidemic modeling framework based on weekly cases using 10-week calibration periods. We report and assess the weekly forecasts with quantified uncertainty from the top-ranked, second-ranked, and ensemble sub-epidemic models. Overall, we conducted 324 weekly sequential 4-week ahead forecasts across the models from the week of July 28th, 2022, to the week of October 13th, 2022.

    Results

    The last 10 of 12 forecasting periods (starting the week of August 11th, 2022) show either a plateauing or declining trend of monkeypox cases for all models and areas of study. According to our latest 4-week ahead forecast from the top-ranked model, a total of 6232 (95% PI 487.8, 12,468.0) cases could be added globally from the week of 10/20/2022 to the week of 11/10/2022. At the country level, the top-ranked model predicts that the USA will report the highest cumulative number of new cases for the 4-week forecasts (median based on OWID data: 1806 (95% PI 0.0, 5544.5)). The top-ranked and weighted ensemble models outperformed all other models in short-term forecasts.

    Conclusions

    Our top-ranked model consistently predicted a decreasing trend in monkeypox cases on the global and country-specific scale during the last ten sequential forecasting periods. Our findings reflect the potential impact of increased immunity, and behavioral modification among high-risk populations.

     
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  6. Abstract Background

    The Mexican Institute of Social Security (IMSS) is the largest health care provider in Mexico, covering about 48% of the Mexican population. In this report, we describe the epidemiological patterns related to confirmed cases, hospitalizations, intubations, and in-hospital mortality due to COVID-19 and associated factors, during five epidemic waves recorded in the IMSS surveillance system.

    Methods

    We analyzed COVID-19 laboratory-confirmed cases from the Online Epidemiological Surveillance System (SINOLAVE) from March 29th, 2020, to August 27th, 2022. We constructed weekly epidemic curves describing temporal patterns of confirmed cases and hospitalizations by age, gender, and wave. We also estimated hospitalization, intubation, and hospital case fatality rates. The mean days of in-hospital stay and hospital admission delay were calculated across five pandemic waves. Logistic regression models were employed to assess the association between demographic factors, comorbidities, wave, and vaccination and the risk of severe disease and in-hospital death.

    Results

    A total of 3,396,375 laboratory-confirmed COVID-19 cases were recorded across the five waves. The introduction of rapid antigen testing at the end of 2020 increased detection and modified epidemiological estimates. Overall, 11% (95% CI 10.9, 11.1) of confirmed cases were hospitalized, 20.6% (95% CI 20.5, 20.7) of the hospitalized cases were intubated, and the hospital case fatality rate was 45.1% (95% CI 44.9, 45.3). The mean in-hospital stay was 9.11 days, and patients were admitted on average 5.07 days after symptoms onset. The most recent waves dominated by the Omicron variant had the highest incidence. Hospitalization, intubation, and mean hospitalization days decreased during subsequent waves. The in-hospital case fatality rate fluctuated across waves, reaching its highest value during the second wave in winter 2020. A notable decrease in hospitalization was observed primarily among individuals ≥ 60 years. The risk of severe disease and death was positively associated with comorbidities, age, and male gender; and declined with later waves and vaccination status.

    Conclusion

    During the five pandemic waves, we observed an increase in the number of cases and a reduction in severity metrics. During the first three waves, the high in-hospital fatality rate was associated with hospitalization practices for critical patients with comorbidities.

     
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  7. Abstract Purpose of Review

    Preparing for pandemics requires a degree of interdisciplinary work that is challenging under the current paradigm. This review summarizes the challenges faced by the field of pandemic science and proposes how to address them.

    Recent Findings

    The structure of current siloed systems of research organizations hinders effective interdisciplinary pandemic research. Moreover, effective pandemic preparedness requires stakeholders in public policy and health to interact and integrate new findings rapidly, relying on a robust, responsive, and productive research domain. Neither of these requirements are well supported under the current system.

    Summary

    We propose a new paradigm for pandemic preparedness wherein interdisciplinary research and close collaboration with public policy and health practitioners can improve our ability to prevent, detect, and treat pandemics through tighter integration among domains, rapid and accurate integration, and translation of science to public policy, outreach and education, and improved venues and incentives for sustainable and robust interdisciplinary work.

     
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  8. null (Ed.)
    Abstract Background Ensemble modeling aims to boost the forecasting performance by systematically integrating the predictive accuracy across individual models. Here we introduce a simple-yet-powerful ensemble methodology for forecasting the trajectory of dynamic growth processes that are defined by a system of non-linear differential equations with applications to infectious disease spread. Methods We propose and assess the performance of two ensemble modeling schemes with different parametric bootstrapping procedures for trajectory forecasting and uncertainty quantification. Specifically, we conduct sequential probabilistic forecasts to evaluate their forecasting performance using simple dynamical growth models with good track records including the Richards model, the generalized-logistic growth model, and the Gompertz model. We first test and verify the functionality of the method using simulated data from phenomenological models and a mechanistic transmission model. Next, the performance of the method is demonstrated using a diversity of epidemic datasets including scenario outbreak data of the Ebola Forecasting Challenge and real-world epidemic data outbreaks of including influenza, plague, Zika, and COVID-19. Results We found that the ensemble method that randomly selects a model from the set of individual models for each time point of the trajectory of the epidemic frequently outcompeted the individual models as well as an alternative ensemble method based on the weighted combination of the individual models and yields broader and more realistic uncertainty bounds for the trajectory envelope, achieving not only better coverage rate of the 95% prediction interval but also improved mean interval scores across a diversity of epidemic datasets. Conclusion Our new methodology for ensemble forecasting outcompete component models and an alternative ensemble model that differ in how the variance is evaluated for the generation of the prediction intervals of the forecasts. 
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  9. In the absence of reliable information about transmission mechanisms for emerging infectious diseases, simple phenomenological models could provide a starting point to assess the potential outcomes of unfolding public health emergencies, particularly when the epidemiological characteristics of the disease are poorly understood or subject to substantial uncertainty. In this study, we employ the modified Richards model to analyze the growth of an epidemic in terms of 1) the number of times cumulative cases double until the epidemic peaks and 2) the rate at which the intervals between consecutive doubling times increase during the early ascending stage of the outbreak. Our theoretical analysis of doubling times is combined with rigorous numerical simulations and uncertainty quantification using synthetic and real data for COVID-19 pandemic. The doubling-time approach allows to employ early epidemic data to differentiate between the most dangerous threats, which double in size many times over the intervals that are nearly invariant, and the least transmissible diseases, which double in size only a few times with doubling periods rapidly growing.

     
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