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  1. 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.


    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.


    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-weekmore »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.


    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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  2. 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.


    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.


    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 hospitalmore »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.


    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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  3. 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 ensemblemore »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.« less
  4. 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.

  5. COVID-19 vaccines have been authorized in multiple countries, and more are under rapid development. Careful design of a vaccine prioritization strategy across sociodemographic groups is a crucial public policy challenge given that 1) vaccine supply will be constrained for the first several months of the vaccination campaign, 2) there are stark differences in transmission and severity of impacts from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across groups, and 3) SARS-CoV-2 differs markedly from previous pandemic viruses. We assess the optimal allocation of a limited vaccine supply in the United States across groups differentiated by age and essential worker status, which constrains opportunities for social distancing. We model transmission dynamics using a compartmental model parameterized to capture current understanding of the epidemiological characteristics of COVID-19, including key sources of group heterogeneity (susceptibility, severity, and contact rates). We investigate three alternative policy objectives (minimizing infections, years of life lost, or deaths) and model a dynamic strategy that evolves with the population epidemiological status. We find that this temporal flexibility contributes substantially to public health goals. Older essential workers are typically targeted first. However, depending on the objective, younger essential workers are prioritized to control spread or seniors to directly control mortality.more »When the objective is minimizing deaths, relative to an untargeted approach, prioritization averts deaths on a range between 20,000 (when nonpharmaceutical interventions are strong) and 300,000 (when these interventions are weak). We illustrate how optimal prioritization is sensitive to several factors, most notably, vaccine effectiveness and supply, rate of transmission, and the magnitude of initial infections.« less
  6. Simple mathematical tools are needed to quantify the threat posed by emerging and re-emerging infectious disease outbreaks using minimal data capturing the outbreak trajectory. Here we use mathematical analysis, simulation and COVID-19 epidemic data to demonstrate a novel approach to numerically and mathematically characterize the rate at which the doubling time of an epidemic is changing over time. For this purpose, we analyze the dynamics of epidemic doubling times during the initial epidemic stage, defined as the sequence of times at which the cumulative incidence doubles. We introduce new methodology to characterize epidemic threats by analyzing the evolution of epidemics as a function of (1) the number of times the epidemic doubles until the epidemic peak is reached and (2) the rate at which the doubling times increase. In our doubling-time approach, the most dangerous epidemic threats double in size many times and the doubling times change at a relatively low rate (e.g., doubling times remain nearly invariant) whereas the least transmissible threats double in size only a few times and the doubling times rapidly increases in the period of emergence. We derive analytical formulas and test and illustrate our methodology using synthetic and COVID-19 epidemic data. Our mathematical analysismore »demonstrates that the series of epidemic doubling times increase approximately according to an exponential function with a rate that quantifies the rate of change of the doubling times. Our analytic results are in excellent agreement with numerical results. Our methodology offers a simple and intuitive approach that relies on minimal outbreak trajectory data to characterize the threat posed by emerging and re-emerging infectious diseases.« less
  7. Wu, Joseph T. (Ed.)
    Colombia announced the first case of severe acute respiratory syndrome coronavirus 2 on March 6, 2020. Since then, the country has reported a total of 5,002,387 cases and 127,258 deaths as of October 31, 2021. The aggressive transmission dynamics of SARS-CoV-2 motivate an investigation of COVID-19 at the national and regional levels in Colombia. We utilize the case incidence and mortality data to estimate the transmission potential and generate short-term forecasts of the COVID-19 pandemic to inform the public health policies using previously validated mathematical models. The analysis is augmented by the examination of geographic heterogeneity of COVID-19 at the departmental level along with the investigation of mobility and social media trends. Overall, the national and regional reproduction numbers show sustained disease transmission during the early phase of the pandemic, exhibiting sub-exponential growth dynamics. Whereas the most recent estimates of reproduction number indicate disease containment, with R t <1.0 as of October 31, 2021. On the forecasting front, the sub-epidemic model performs best at capturing the 30-day ahead COVID-19 trajectory compared to the Richards and generalized logistic growth model. Nevertheless, the spatial variability in the incidence rate patterns across different departments can be grouped into four distinct clusters. As themore »case incidence surged in July 2020, an increase in mobility patterns was also observed. On the contrary, a spike in the number of tweets indicating the stay-at-home orders was observed in November 2020 when the case incidence had already plateaued, indicating the pandemic fatigue in the country.« less
  8. Adrish, Muhammad (Ed.)
    Mexico has experienced one of the highest COVID-19 mortality rates in the world. A delayed implementation of social distancing interventions in late March 2020 and a phased reopening of the country in June 2020 has facilitated sustained disease transmission in the region. In this study we systematically generate and compare 30-day ahead forecasts using previously validated growth models based on mortality trends from the Institute for Health Metrics and Evaluation for Mexico and Mexico City in near real-time. Moreover, we estimate reproduction numbers for SARS-CoV-2 based on the methods that rely on genomic data as well as case incidence data. Subsequently, functional data analysis techniques are utilized to analyze the shapes of COVID-19 growth rate curves at the state level to characterize the spatiotemporal transmission patterns of SARS-CoV-2. The early estimates of the reproduction number for Mexico were estimated between R t ~1.1–1.3 from the genomic and case incidence data. Moreover, the mean estimate of R t has fluctuated around ~1.0 from late July till end of September 2020. The spatial analysis characterizes the state-level dynamics of COVID-19 into four groups with distinct epidemic trajectories based on epidemic growth rates. Our results show that the sequential mortality forecasts from themore »GLM and Richards model predict a downward trend in the number of deaths for all thirteen forecast periods for Mexico and Mexico City. However, the sub-epidemic and IHME models perform better predicting a more realistic stable trajectory of COVID-19 mortality trends for the last three forecast periods (09/21-10/21, 09/28-10/27, 09/28-10/27) for Mexico and Mexico City. Our findings indicate that phenomenological models are useful tools for short-term epidemic forecasting albeit forecasts need to be interpreted with caution given the dynamic implementation and lifting of social distancing measures.« less