LLM-Augmented Computational Phenotyping of Long Covid

Due to the limited amount of information, modeling longitudinal rare-disease data can benefit from integrating clinical knowledge. Yet, elicitation of expert knowledge and formalization for model fitting is challenging, in particular due to limited time of clinical experts. To nevertheless make domain knowledge accessible during model fitting, we use large language models (LLMs) as synthetic clinical experts to supervise a variational-autoencoder-based approach that learns low-dimensional latent summaries of visit-level observations. Specifically, LLMs are queried offline on textual descriptions of patient observations to obtain judgments, e.g., the suspected clinical category. To improve the variational autoencoder fit, we train a differentiable surrogate model on these judgments and augment the loss function to encourage reconstructions that preserve the clinical-label distribution of their corresponding input profile. In an application to longitudinal motor-function assessments from children with spinal muscular atrophy, we map visit-level clinical profiles to low-dimensional representations that are linked by a multivariate mixed-effects model. The synthetic expert loss discourages reconstructions that remain numerically close in data space but alter the clinical interpretation of the reconstructed motor function profile, such as by crossing a disease-type boundary. We thus reduced disagreement between original and reconstructed SMA type labels from about 11 to 7 percent. Furthermore, informing the latent representation by the synthetic expert improved prediction of motor function milestones compared with unsupervised latent representations and a data-level baseline. These results suggest that incorporating LLMs into model fitting can make clinical knowledge available to representation learning and improve clinical faithfulness for longitudinal rare-disease data.

As large language models empower healthcare, intelligent clinical decision support has developed rapidly. Longitudinal electronic health records (EHR) provide essential temporal evidence for accurate clinical diagnosis and analysis. However, current large language models have critical flaws in longitudinal EHR reasoning. First, lacking fine-grained statistical reasoning, they often hallucinate clinical trends and metrics when quantitative evidence is textually implied, biasing diagnostic inference. Second, non-uniform time series and scarce labels in longitudinal EHR hinder models from capturing long-range temporal dependencies, limiting reliable clinical reasoning. To address the above limitations, this work presents the Probabilistic Chain-of-Thought Completion Agent (COTCAgent), a hierarchical reasoning framework for longitudinal electronic health records. It consists of three core modules. The Temporal-Statistics Adapter (TSA) converts analytical plans into executable code for standardized trend output. The Chain-of-Thought Completion (COTC) layer leverages a symptom-trend-disease knowledge base with weighted scoring to evaluate disease risk, while the bounded completion module acquires structured evidence through standardized inquiries and iterative scoring constraints to ensure rigorous reasoning. By decoupling statistical computation, feature matching, and language generation, the framework eliminates reliance on complex multi-modal inputs and enables efficient longitudinal record analysis with lower computational overhead. Experimental results show that COTCAgent powered by Baichuan-M2 achieves 90.47% Top-1 accuracy on the self-built dataset and 70.41% on HealthBench, outperforming existing medical agents and mainstream large language models. The code is available at https://github.com/FrankDengAI/COTCAgent/.

Long COVID (LC) poses a challenge for clinical decision support because relevant evidence is distributed across sources with different update cycles, evidentiary roles, and levels of clinical maturity. We present a clinician-facing chatbot that organizes four sources within a retrieval-augmented workflow: expert-curated consensus guidance, current PubMed literature, registered interventional trials, and evidence from living systematic reviews. Consensus guidance is always included to frame responses, while the remaining sources are retrieved in parallel when selected by the user. In an exploratory automated evaluation on 50 clinician-facing questions, our chatbot showed comparable mean ratings to OpenEvidence, with numerically higher scores and lower score variability in an LLM-judged comparison.