Prospective multi-pathogen disease forecasting using autonomous LLM-guided tree search

Epidemic LLM forecasters are usually trained and evaluated as static supervised models, whereas operational pandemic forecasting is a streaming process in which labels arrive after predictions and disease regimes shift over time. We study this mismatch in weekly COVID-19 hospitalization trend forecasting across five variant regimes. We introduce EpiEvolve, a self-evolving agent that wraps an LLM forecaster trained on the warm-start period and keeps its weights fixed during streaming. EpiEvolve adapts by storing forecast outcomes in a hierarchical episodic memory, reflecting on delayed labels, retrieving cases relevant to the current regime, and distilling recurring errors into strategic rules. The resulting context lets the forecaster reuse its own past predictions and outcomes in later weeks while following a chronological protocol that prevents future leakage. On the streaming dataset, EpiEvolve reaches $0.629$ average accuracy, compared with $0.561$ for the static backbone and $0.325$ for the external CDC ensemble, and reduces recovery lag after regime shifts from $5$ to $2$ weeks. Ablations show that reflection, strategic memory, and regime-aware retrieval each contribute to the gains.

Medical and public health experts must make real-time resource decisions, such as expanding hospital bed capacity, based on projected hospitalization trends during large-scale healthcare disruptions (e.g., operational failures or pandemics). Forecasting models can assist in this task by analyzing large volumes of resource-related data at the facility level, but they must be reliable for decision-making under real-world data conditions. Recent work shows that large language models (LLMs) can incorporate richer forms of context into numerical forecasting. Whereas traditional models rely primarily on temporal context (i.e., past observations), LLMs can also leverage non-temporal public health context such as demographic, geographic, and population-level features. However, it remains unclear how these models should be used to produce stable or decision-relevant predictions in real-world healthcare settings. To evaluate how LLMs can be effectively used in this setting, we evaluate three approaches across 60 counties with low-,mid-, and high-hospitalization intensities in the United States: direct LLM-based forecasting, classical time-series models, and a context-augmented hybrid pipeline (HybridARX) that incorporates LLM-derived signals into structured models. Because the goal is operational decision-making rather than error minimization alone, we evaluate performance with bias and lead-lag alignment in addition to standard forecasting metrics. Our results show that HybridARX improves over classical ARX by yielding more stable and better-calibrated forecasts, particularly when incorporating noisy contextual signals into structured time-series models. These findings suggest that, in non-stationary healthcare resource forecasting, LLMs are most useful when embedded within structured hybrid models.

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.