Beyond Single-Pathogen Forecasts: Predicting Shared Respiratory Hospital Burden from Influenza, COVID-19, and RSV

Wastewater-based surveillance is an effective tool for disease monitoring and can provide early warning of outbreaks. Although wastewater viral loads (WVL) correlate with disease burden, their utility for improving real-time forecasting remains under investigation. During the early phases of an epidemic, many indicators can effectively monitor disease spread, but their reliability may decline because of reporting fatigue and low prevalence. Hospital burden can vary substantially even during low-prevalence periods, making accurate forecasting of burden indicators essential for minimizing disease impacts. In this paper, we present principled approaches for processing wastewater data, characterizing its relationship with burden indicators, and generating real-time forecasts. We assess the predictability of WVL using entropy measures. We analyze the relationship between WVL and burden indicators using causality tests that capture temporal dynamics and the leading-indicator behavior of WVL. We incorporate these insights into a time-varying forecasting model that accounts for the evolving relationship between the signals. We also evaluate the effects of delays in WVL reporting through simulations. We test the utility of our methods by forecasting COVID-19 hospital admissions across Virginia and its health regions during periods of varying disease prevalence. Incorporating WVL improves forecast accuracy relative to baseline models, particularly during critical epidemic phases, and results in a 20 percentage point improvement in forecast coverage. Our results demonstrate that WVL signals can improve infectious disease forecasting even under conditions of low prevalence or delayed reporting.

Seasonal influenza infects millions of people and causes substantial morbidity and mortality in the United States each year, making accurate short-term forecasting a core public-health need. Reliable forecasts of epidemic time series can inform vaccination timing, hospital staffing, and resource allocation, yet the comparative behavior of modern forecasting architectures on infectious-disease surveillance data remains insufficiently characterized. We address this gap through a systematic evaluation of regional influenza forecasting using influenza-like illness surveillance and influenza-associated hospitalization time series under both temporal and spatial generalization settings for 1-4-week-ahead prediction. We compare classical neural network architectures, numerical transformer-based models, pretrained time series foundation models, and LLM-based forecasting approaches. Across tasks, we demonstrate that a mixture-of-experts model that fuses multiple pretrained forecasters achieves the strongest overall performance, indicating that heterogeneous pretrained representations provide complementary predictive information. Our results further show that numerical transformer-based models produce reliable forecasts, while pretraining provides the largest gains at longer horizons, particularly when the pretraining domain is mechanistically aligned with influenza dynamics. In contrast, LLM-based time series methods underperform relative to numerical forecasters in this setting. Finally, we examine hospitalization information as both an auxiliary covariate and a pretraining source. Hospitalization signals provide complementary improvements in selected settings and clarify when additional surveillance streams enhance the robustness of multi-horizon forecasting. These findings provide actionable guidance on model selection, pretraining strategy, and auxiliary-signal use for influenza preparedness.

Forecasting infectious disease incidence can provide important information to guide public health planning, yet is difficult because epidemic dynamics are complex. Current mechanistic and statistical approaches often struggle to capture multimodal uncertainty or emergent trends. Influpaint adapts denoising diffusion probabilistic models to epidemic forecasting. By encoding influenza seasons as spatiotemporal images in which pixel intensity represents incidence, Influpaint learns a rich distribution of disease dynamics from a hybrid dataset of surveillance and simulated trajectories. Forecasting is formulated as a conditional generation (inpainting) task from partial observations. We show that Influpaint generates realistic, diverse epidemic trajectories and achieves forecast accuracy that is competitive with leading ensemble methods in retrospective evaluation. In real-time evaluation during the 2023--2025 U.S. CDC FluSight challenges, performance improved substantially across seasons, with highly accurate but somewhat overconfident projections in 2024--2025. The best performance was achieved with a training dataset containing 30% surveillance and 70% simulated trajectories. These results show that diffusion models can capture important spatiotemporal structure in influenza dynamics and provide a flexible framework for probabilistic infectious disease forecasting.