Integrating adaptive human behavior into epidemic models with large language models

Infectious disease transmission is shaped by patterns of human interaction, which adapt as epidemic conditions change. Capturing these context-dependent behaviors remains a fundamental challenge for epidemic models. Here, we recast this challenge by using large language models (LLMs) to represent adaptive human behavior within mechanistic epidemic models. We operationalize this idea through Generative Adaptive Behavioral Layer for Epidemics (GABLE), which adapts LLMs to infer behavioral responses to epidemic and policy conditions and translates them into age-structured contact matrices coupled to a mechanistic epidemic model. Applied to COVID-19 in France, GABLE reproduced responses in population mixing and age-specific contact structures that remained epidemiologically informative. In short-term forecasting, LLM-generated contact matrices outperformed mobility-driven matrices derived from real-world mobility data, with the largest gains at longer horizons. GABLE also extends beyond forecasting to prospective policy evaluation by projecting behavioral and epidemic responses to candidate interventions before implementation. When supplied with subsequently implemented policies, GABLE reproduced epidemic trajectories and generated distinct responses to alternative policy timing and composition. By leveraging LLMs as a flexible behavioral layer, GABLE provides a framework for coupling context-sensitive behavioral generation with epidemic dynamics.

GeoID-PINN: Identifiability-Aware Regional Epidemic Inference with Geographic Coupling

Regional surveillance data reflect local transmission, reporting, seeding, and external infection pressure, which are difficult to identify separately. We introduce GeoID-PINN, a physics-informed neural network (PINN) for susceptible-infectious-recovered-deceased (SIRD) dynamics. The model represents spatial dependence with a row-stochastic source-composition matrix whose rows assign nonnegative source weights that sum to one. We regularize this matrix toward a spatial prior constructed from distance, adjacency, commuting, or lead-lag information. In a four-region simulation with known truth, a compatible distance prior gives source-composition error 0.099. The error rises to 0.159 without regularization and 0.577 under a strongly misspecified prior, while trajectory fit and transmission-scale estimates remain similar. Accurate trajectories therefore do not guarantee recovery of the regional dependence structure. We also evaluate GeoID-PINN retrospectively using COVID-19 data from 64 Louisiana counties. Relative to an autoregressive negative-binomial baseline, Forecast-Trained Geo-PINN reduces mean squared error (MSE) from 32,957 to 11,468 and mean absolute error (MAE) from 70.60 to 57.73. The baseline has lower negative log likelihood (NLL), 5.158 versus 5.346, indicating better distributional fit but worse point accuracy. In a controlled 15-county comparison, county adjacency reduces MSE by 6.85 percent and MAE by 3.1 percent. Similar performance across plausible priors supports structured regularization but not unique edge recovery. These results require prior-sensitivity and observation-model checks before interpretation.

A Koopman-PINN Framework for Epidemic Models: Parameter Inference and Forecasting

We propose a Koopman-enhanced physics-informed neural network (K--PINN) framework for parameter inference and forecasting in nonlinear epidemic models. This method combines Koopman operator theory and physics-informed learning. It maps epidemic states into a latent observable space where the dynamics evolve approximately linearly while satisfying the governing epidemic equations through automatic differentiation. This integration improves interpretability, parameter identifiability, and long-term predictive stability. We apply the proposed framework to a normalized SEIRSD epidemic model and evaluate it using synthetic monkeypox (Mpox) data and real-world datasets from Germany, Morocco, and Sweden for the SARS-CoV-2 virus. Synthetic trajectories are generated using a structure-preserving, nonstandard finite difference scheme to ensure reliable training data. Numerical results demonstrate that K--PINN achieves more accurate parameter estimation, trajectory reconstruction, and long-term forecasting than classical PINNs and Koopman-EDMD approaches. These results suggest that K--PINN is an effective machine learning framework for epidemic modeling that can be extended to more complex systems.

Benchmarking Counterfactual Prediction in Epidemic Time Series with Time-Varying Interventions

Deep learning has enabled significant advances in time-series causal inference, yet progress remains constrained by the lack of realistic benchmarks with observable counterfactual outcomes. Existing datasets either rely on real-world observations without ground-truth counterfactuals or on simplified simulations that fail to capture complex causal dynamics. To address this gap, we develop a large-scale benchmark for counterfactual prediction in epidemic time series under dynamic interventions. Unlike existing benchmarks, it supports static and time-varying treatments, as well as both single-policy and multi-policy intervention settings, enabling evaluation of causal inference methods across a broad range of causal inference scenarios. Leveraging a calibrated agent-based model grounded in real-world demographic, mobility, epidemiological, and policy data, we generate realistic counterfactual trajectories across more than 150 U.S. counties. Using this benchmark, we evaluate widely used and state-of-the-art causal inference methods, revealing substantial performance differences and highlighting the challenges of realistic time-series causal reasoning.

Neetyabhas: A Framework for Uncertainty-Aware Public Policy Optimization in Rational Agent-Based Models

Purpose The WHO's COVID-19 non-pharmaceutical interventions (e.g., lockdowns, vaccinations) effectively curb transmission but impose heavy economic strains. Existing research often neglects individual behaviors and falsely assumes perfect infection tracking and flawless policy execution, failing to account for real-world uncertainties and errors. Methods We propose an integrative approach incorporating uncertainties in both epidemic measurement (infections/hospitalizations) and policy implementation. We built a simulation model of 1,000 individuals making real-time choices regarding mask-wearing, vaccination, and shopping. Concurrently, policymakers deploy interventions (lockdowns, mandates) based on health and economic observations. This framework is driven by hierarchical reinforcement learning agents, utilizing deep Q-networks alongside uncertainty-aware policy gradient variants (DDPG and TD3). Results The simulations effectively managed the epidemic's progression. Masking and vaccinations proved highly effective, significantly reducing both the outbreak's peak height and duration. By integrating individual behaviors, policy uncertainties, and multifaceted interventions, our dynamic control approach successfully mitigated the epidemic's impact. Conclusions Our model overcomes previous research limitations by embedding uncertainty and human behavior into public health policy frameworks. The simulation demonstrates that accounting for individual choices and imperfect data is crucial for designing effective interventions during complex pandemics, with masks and vaccines serving as pivotal tools.

Neural Posterior Estimation for Stochastic Epidemic Models Using Final Outcome Data

Neural posterior estimation (NPE) is a simulation-based approach to Bayesian inference that trains a neural network to approximate the posterior distribution from simulated parameter - data pairs, bypassing likelihood evaluation. We apply NPE -- to our knowledge for the first time -- to stochastic susceptible-infectious-removed (SIR) epidemic models observed through final outcome data, considering both homogeneously mixing and household-structured populations. Such data arise naturally in retrospective outbreak investigations and household transmission studies, yet inference is computationally challenging: data-augmentation Markov chain Monte Carlo (MCMC) can be slow to mix in large populations and difficult to implement, while Approximate Bayesian Computation (ABC) suffers from low acceptance rates, particularly for large populations or unlikely outcomes. The discrete, low-dimensional nature of such observations makes this setting particularly well suited to NPE. We show that a logNormal posterior approximation, parameterised by a feed-forward neural network, accurately recovers reference posteriors across a range of population sizes and transmission regimes, and extends naturally to joint inference on global and local transmission rates in the household model. Once trained, the network produces approximate posterior distributions in seconds and generalises reliably to population sizes and structures not seen during training. Performance on both synthetic and real outbreak datasets is consistently strong, with results in close agreement with published analyses.