Alessandro Vespignani

Infectious disease forecasting supports public health preparedness and response by informing resource allocation, intervention planning, and situational awareness. Infectious disease forecasting capabilities in the United States have grown over the past decade yet whether forecast quality has improved over this time remains unclear. Current evaluation metrics describe relative performance for a common set of forecast targets but cannot evaluate performance across different outcomes, seasons, and pathogens. We addressed this challenge by developing a novel skill score metric to assess forecasts based on performance relative to two benchmark models: a hindcast as an idealized upper bound of performance and a baseline model as a minimal performance standard. To study the impact of the baseline choice, we considered three types of baseline models with varying levels of complexity. Using this skill score framework, we retrospectively evaluated short-term influenza (influenza-like illness and hospitalization) and COVID-19 (case, death, and hospitalization) forecasts, focusing on how the performance of team and multi-model ensemble forecasts changed over time. The ensemble outperformed 99% of forecasts from a simplistic, naïve baseline, and 84-91% of forecasts from more complex baseline models that incorporate recent data. We found consistent improvements in ensemble and team forecast skill over time for both influenza forecast targets, with 4-week horizon forecasts in the most recent year having higher skill scores than 1-week horizon forecasts in the first year of each challenge. Results were mixed for COVID-19 forecasts. This framework provides a comprehensive picture of progress in infectious disease forecasting over the past decade enabled by improved standardization, data, models, and collaboration.

In recent years, the use of multi-model ensemble projections in infectious disease modeling has become an established methodological approach to account for and integrate across uncertainties and structural differences present in individual models. However, the creation of long-term ensemble projections through these coordinated efforts is resource-intensive, demanding the input of multiple research teams and substantial computational power. This typically limits the ability to refine projections, update the selection of plausible epidemic trajectories, or expand the number of scenarios that can be assessed, even as new empirical data become available. To address this challenge, we define an adaptive ensemble approach that, analogously to a multi-model particle filtering method, dynamically selects individual model trajectories based on observed data throughout the epidemic projection period. We demonstrate the effectiveness of this methodology using the U.S. Flu Scenario Modeling Hub (SMH) projections for influenza hospitalizations in the United States during the 2023-2024 and 2024-2025 winter seasons. Our findings show that the adaptive ensemble yields improved predictive accuracy with respect to the original SMH ensemble projections across several scoring rules and geographical resolutions. Furthermore, the adaptive ensemble approach offers two additional applications: i) the dynamic assignment of posterior probabilities to epidemic scenarios, identifying the most plausible scenario, and representing how reality is captured by a combination of scenarios, and ii) the potential use for short-term forecasting. The adaptive ensemble approach is able to identify the most likely scenarios for the 2023-2024 and 2024-2025 U.S. influenza seasons, even in the early stages of the epidemic. It outperforms, retrospectively, a baseline model in short-term forecasting of influenza hospitalizations in the United States during the two seasons across various horizons and scoring rules, showing potential to contribute to real-time collaborative forecasting challenges such as CDC’s FluSight. The proposed approach offers an efficient or low-resource strategy to increase the impact of multi-model epidemic projections by providing real-time support to modeling teams, public health authorities, and decision-makers.

Background: The 2026 FIFA World Cup may bring over one million visitors to North America from around the globe to participate in mass gathering events. The nature of the event and recent news have raised concerns for some that the tournament could lead to infectious disease outbreaks or fuel existing epidemics. Objective: To systematically assess the infectious disease threat posed to the United States by the tournament. Design: A multi-institutional team evaluated pathogen-specific risk across three dimensions: importation, outbreak potential, and impact to identify a priority pathogen list. A systematic screening protocol ensured common criteria and that pathogen information was collected when necessary to inform inclusion. Results: Increased risk from the World Cup is near zero for 63 of 77 evaluated pathogens. Pathogens were predominantly excluded as threats due to low excess importation risk and low outbreak potential if introduced. The remaining priority pathogens fall into five categories: (a) mosquito borne pathogens with the potential for sustained transmission in some host cities, (b) seasonal respiratory viruses, (c) chronic infections with high prevalence outside the United States, (d) pathogens present in the United States with likely increased transmission at World Cup activities, and (e) high-consequence infectious threats. Limitations: Data availability is variable across diseases. Impact calculations may not reflect actual costs to host cities. Disease incidence in World Cup travelers may differ from national incidence rates. Conclusion: While infectious disease outbreaks at the 2026 FIFA World Cup are possible, in an already highly connected world where large gatherings are frequent, the elevated risk from the tournament is not as extreme as it first may seem. Primary Funding Source: US Centers for Disease Control and Prevention

Human mobility, climate change and demographic trends increase the risk of pathogen spillover and expansion. Data that can inform our responses to outbreaks have increased in availability and volume, but access to highly confidential outbreak data and commercially sensitive contextual information remains difficult. Despite ongoing efforts to adopt global health data infrastructures and sharing protocols, there remain regulatory, logistical, human and computational barriers to data sharing. Federated approaches—in which data remain stored locally but analyses are performed across datasets from different sources—offer a potential way to address these challenges. While federated approaches have been used in some clinical and biomedical contexts, their adoption in infectious disease surveillance and modeling has been limited. Here, we discuss global approaches to infectious disease modeling and analysis, with a focus on federated methods. We outline how these can be used to address key epidemiological questions during outbreaks by enabling the secure use of multimodal data and integration with existing surveillance and modeling efforts. We summarize current methods for combining distributed and locally stored data and identify limitations, opportunities and organizational structures needed to achieve equitable global public health impacts.

Six years after its emergence, SARS-CoV-2 continues to have a substantial burden, however, the impact of vaccination and the optimal timing of its rollout remain uncertain. To explore these uncertainties, the US Scenario Modeling Hub convened its 19th round of ensemble projections for COVID-19 hospitalizations and deaths in the United States. Eight teams provided outcomes for each US state and nationally from April 2025 to April 2026 under five scenarios regarding vaccine recommendations and timing. We assessed recommendations with two eligibility scenarios (high-risk individuals only and all-eligible) and two timing scenarios (classic start: mid-August, earlier start: late June). These were crossed to create four scenarios and were compared against a counterfactual scenario with no vaccination. We found that compared to no vaccination, our ensemble projections estimated 90,000 (95% PI 53,000-126,000) hospitalizations averted in the high-risk and classic timing scenario across the US. Expanding coverage averted an additional 26,000 (95% PI 14,000-39,000) hospitalizations, which when coupled with earlier vaccination timing further reduced national hospitalizations by 15,000 (95% PI −3,000-33,000). These findings estimate significant benefits from a broad all-eligible vaccination recommendation, and suggest an additional benefit is likely to be gained from an earlier vaccination campaign.

Infectious disease spread is a multiscale process composed of within-host (biological) and between-host (social) drivers and disentangling them from each other is a central challenge in epidemiology. Here, we introduce VIBES, a multiscale modeling framework that explicitly integrates viral dynamics based on patient-level data with population-level transmission on a data-driven network of social contacts. Using SARS-CoV-2 as a case study, we analyze three emergent epidemic properties, namely the generation time, serial interval, and presymptomatic transmission. First, we established a purely biological baseline, thus independent of the reproduction number ( R ), from the within-host model, estimating a generation time of 6.3 d for symptomatic individuals and 43.1% presymptomatic transmission. Then, using the full model incorporating social contacts, we found a shorter generation time (5.4 d at R = 3.0) and an increase in presymptomatic transmission (52.8% at R = 3.0), disentangling the impact of social drivers from a purely biological baseline. We further show that as pathogen transmissibility increases ( R from 1.3 to 6), competition among infectious individuals shortens the generation time and serial interval by up to 21% and 13%, respectively. Conversely, a social intervention, like isolation, increases the proportion of presymptomatic transmission by about 30%. Our framework also estimates metrics that are challenging to obtain empirically, such as the generation time for asymptomatic individuals (5.6 d; 95%CI: 5.1 to 6.0 at R = 1.3). Our findings establish multiscale modeling as a powerful tool for mechanistically quantifying how pathogen biology and human social behavior shape epidemic dynamics as well as for assessing public health interventions.

We present results from the second season of Influcast, a multi-model collaborative forecasting hub focused on influenza in Italy. During the 2024/25 winter season, Influcast collected one- to four-week-ahead probabilistic forecasts of influenza-like illness (ILI) incidence alongside influenza A and B ILI+ incidence signals. New ILI+ targets were constructed integrating syndromic surveillance data with virological detections collected weekly by the Italian National Institute of Health. Forecasts were submitted by six independent models (including compartmental, metapopulation, and statistical approaches) and combined into an ensemble. Ensemble forecasts for ILI+ consistently outperformed both the baseline (a naive persistence model) and most individual models in terms of Weighted Interval Score (WIS), Absolute Error (AE), and prediction coverage. Importantly, ensemble ILI+ forecasts achieved significantly lower WIS and AE ratios (i.e., ratio between the ensemble and the baseline models) and improved calibration compared to ILI forecasts. Our findings support the integration of virological surveillance data in forecasting target definition to improve the reliability of epidemic forecasts and strengthen their utility for situational awareness, communication, and targeted intervention.