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The integration of viral genomic data into public health surveillance has revolutionized our ability to track and forecast infectious disease dynamics. This review addresses two critical aspects of infectious disease forecasting and monitoring: the methodological workflow for epidemic forecasting and the transformative role of molecular surveillance. We first present a detailed approach for validating epidemic models, emphasizing an iterative workflow that utilizes ordinary differential equation (ODE)-based models to investigate and forecast disease dynamics. We recommend a more structured approach to model validation, systematically addressing key stages such as model calibration, assessment of structural and practical parameter identifiability, and effective uncertainty propagation in forecasts. Furthermore, we underscore the importance of incorporating multiple data streams by applying both simulated and real epidemiological data from the COVID-19 pandemic to produce more reliable forecasts with quantified uncertainty. Additionally, we emphasize the pivotal role of viral genomic data in tracking transmission dynamics and pathogen evolution. By leveraging advanced computational tools such as Bayesian phylogenetics and phylodynamics, researchers can more accurately estimate transmission clusters and reconstruct outbreak histories, thereby improving data-driven modeling and forecasting and informing targeted public health interventions. Finally, we discuss the transformative potential of integrating molecular epidemiology with mathematical modeling to complement and enhance epidemic forecasting and optimize public health strategies. 

The 2022–2023 mpox outbreak exhibited an uneven global distribution. While countries such as the UK, Brazil, and the USA were most heavily affected in 2022, many Asian countries, specifically China, Japan, South Korea, and Thailand, experienced the outbreak later, in 2023, with significantly fewer reported cases relative to their populations. This variation in timing and scale distinguishes the outbreaks in these Asian countries from those in the first wave. This study evaluates the predictability of mpox outbreaks with smaller case counts in Asian countries using popular epidemic forecasting methods, including the ARIMA, Prophet, GLM, GAM, n-Sub-epidemic, and Sub-epidemic Wave frameworks. Despite the fact that the ARIMA and GAM models performed well for certain countries and prediction windows, their results were generally inconsistent and highly dependent on the country, i.e., the dataset, as well as the prediction interval length. In contrast, n-Sub-epidemic Ensembles demonstrated more reliable and robust performance across different datasets and predictions, indicating the effectiveness of this model on small datasets and its utility in the early stages of future pandemics. 

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. 

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. 

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.