Mantis: A Simulation-Grounded Foundation Model for Disease Forecasting

Abstract: Infectious disease forecasting in novel outbreaks or low resource settings has been limited by the need for disease-specific data, bespoke training, and expert tuning. We introduce Mantis, a foundation model trained entirely on mechanistic simulations, which enables out-of-the-box forecasting across diseases, regions, and outcomes, even in settings with limited historical data. Mantis is built on over 400 million simulated days of outbreak dynamics spanning diverse pathogens, transmission modes, interventions, and surveillance artifacts. Despite requiring no real-world data during training, Mantis outperformed 39 expert-tuned models we tested across six diseases, including all models in the CDC's COVID-19 Forecast Hub. Mantis generalized to novel epidemiological regimes, including diseases with held-out transmission mechanisms, demonstrating that it captures fundamental contagion dynamics. Critically, Mantis is mechanistically interpretable, enabling public health decision-makers to identify the latent drivers behind its predictions. Finally, Mantis delivers accurate forecasts at 8-week horizons, more than doubling the actionable range of most models, enabling proactive public health planning. Together, these capabilities position Mantis as a foundation for next-generation disease forecasting systems: general, interpretable, and deployable where traditional models fail.