UDCA May Promote COVID-19 Recovery: A Cohort Study with AI-Aided Analysis

To investigate the impact of ursodeoxycholic acid (UDCA) treatment on the clinical outcome of mild and moderate COVID-19 cases, a retrospective analysis was conducted to evaluate the efficacy of UDCA on patients diagnosed with COVID-19 during the peak of the Omicron outbreak in China. This study presents promising results, demonstrating that UDCA significantly reduced the time to Body Temperature Recovery after admission and a higher daily dose seems to be associated with a better outcome without observed safety concerns. We also introduced VirtualBody, a physiologically plausible artificial neural network model, to generate an accurate depiction of the drug concentration-time curve individually, which represented the absorption, distribution, metabolism, and excretion of UDCA in each patient. It exhibits exceptional performance in modeling the complex PK-PD profile of UDCA, characterized by its endogenous and enterohepatic cycling properties, and further validates the effectiveness of UDCA as a treatment option from the drug exposure-response perspective. Our work highlights the potential of UDCA as a novel treatment option for periodic outbreaks of COVID-19 and introduces a new paradigm for PK-PD analysis in retrospective studies to provide evidence for optimal dosing strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by National Key Research and Development Program of China (2020AAA0107200), National Science Foundation of China (61921006), Jiangsu Provincial Natural Science Fund for Distinguished Young Scholars (BK20200005) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Nanjing University Hospital institutional review boards approved this study as minimal risk and waived informed consent requirements. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.