Predicting Trajectories of Long COVID in Adult Women: The Critical Role of Causal Disentanglement

Early prediction of Post-Acute Sequelae of SARS-CoV-2 severity is a critical challenge for women's health, particularly given the diagnostic overlap between PASC and common hormonal transitions such as menopause. Identifying and accounting for these confounding factors is essential for accurate long-term trajectory prediction. We conducted a retrospective study of 1,155 women (mean age 61) from the NIH RECOVER dataset. By integrating static clinical profiles with four weeks of longitudinal wearable data (monitoring cardiac activity and sleep), we developed a causal network based on a Large Language Model to predict future PASC scores. Our framework achieved a precision of 86.7\% in clinical severity prediction. Our causal attribution analysis demonstrate the model's ability to differentiate between active pathology and baseline noise: direct indicators such as breathlessness and malaise reached maximum saliency (1.00), while confounding factors like menopause and diabetes were successfully suppressed with saliency scores below 0.27.

LLM-Augmented Computational Phenotyping of Long Covid

Phenotypic characterization is essential for understanding heterogeneity in chronic diseases and for guiding personalized interventions. Long COVID, a complex and persistent condition, yet its clinical subphenotypes remain poorly understood. In this work, we propose an LLM-augmented computational phenotyping framework ``Grace Cycle'' that iteratively integrates hypothesis generation, evidence extraction, and feature refinement to discover clinically meaningful subgroups from longitudinal patient data. The framework identifies three distinct clinical phenotypes, Protected, Responder, and Refractory, based on 13,511 Long Covid participants. These phenotypes exhibit pronounced separation in peak symptom severity, baseline disease burden, and longitudinal dose-response patterns, with strong statistical support across multiple independent dimensions. This study illustrates how large language models can be integrated into a principled, statistically grounded pipeline for phenotypic screening from complex longitudinal data. Note that the proposed framework is disease-agnostic and offers a general approach for discovering clinically interpretable subphenotypes.