Amar Sra

Jing Wang, Jie Shen, Amar Sra et al.

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.

Jing Wang, Tong Zhang, Xing Niu et al.

Post-acute sequelae of SARS-CoV-2 infection (Long COVID) frequently persists for months, yet drivers of clinical remission remain incompletely defined. Here we analyzed 97,564 longitudinal PASC assessments from 13,511 participants with linked vaccination histories to disentangle passive temporal progression from vaccine-associated change. Using a clinically validated threshold (PASC $\geq 12$), trajectories separated into three phenotypes: Protected (persistently sub-threshold), Refractory (persistently symptomatic), and Responders (transitioning from symptomatic to recovered). Across the full cohort, symptom severity increased modestly with elapsed time ($r=0.0521$, $P=1.26\times10^{-59}$), whereas cumulative vaccination showed an inverse association with severity ($r=-0.0434$, $P=5.95\times10^{-42}$). In summary, baseline Long COVID severity appears clinically deterministic. In the absence of intervention, symptoms typically persist without spontaneous resolution. Recovery is primarily associated with repeated immunization.

Jing Wang, Jie Shen, Yiming Luo et al.

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.

Jing Wang, Amar Sra, Jeremy C. Weiss

The long-term effects of Postacute Sequelae of SARS-CoV-2, known as PASC, pose a significant challenge to healthcare systems worldwide. Accurate identification of progression events, such as hospitalization and reinfection, is essential for effective patient management and resource allocation. However, traditional models trained on structured data struggle to capture the nuanced progression of PASC. In this study, we introduce the first publicly available cohort of 18 PASC patients, with text time series features based on Large Language Model Llama-3.1-70B-Instruct and clinical risk annotated by clinical expert. We propose an Active Attention Network to predict the clinical risk and identify progression events related to the risk. By integrating human expertise with active learning, we aim to enhance clinical risk prediction accuracy and enable progression events identification with fewer number of annotation. The ultimate goal is to improves patient care and decision-making for SARS-CoV-2 patient.