UDCA May Promote COVID-19 Recovery: A Cohort Study with AI-Aided Analysis
Yang Yu, Guo Yu, Lu-Yao Han, Jian Li, Zhi-Long Zhang, Tian-Shuo Liu, Ming-Feng Li, De-Chuan Zhan, Shao-Qiu Tang, Zhi-Hua Zhou, Guang-Ji Wang
doi:10.1101/2023.05.02.23289410
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. The COVID-19 pandemic has caused an enormous global burden on public health, affecting civil societies, and hindering economic development 1 . In China, the number of COVID-19 infections skyrocketed in November 2022, following the government's active optimization and refinement of its COVID-19 response. The most prevalent strains were BA.5.2 (70.8%) and BF.7 (23.4%) 2,3 . Therefore, given the emergence of new variants and the persistent risk of periodic outbreaks during the era of Omicron, the need for accessible, oral therapeutic options to treat COVID-19 remains urgent, especially for individuals who have already been vaccinated 4-6 . Currently, only two oral antivirals, ritonavir-boosted nirmatrelvir and molnupiravir, have been approved for the treatment of mild or moderate COVID-19 under Emergency Use Authorization 7-10 . However, their availability is predominantly limited to individuals with affluent financial resources, and their efficacy against the Omicron (B.1.1.529) variant in vaccinated patients is not well established. Recent studies have explored the potential of UDCA, a classic FXR inhibitor, as a treatment option for COVID-
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'abstract': '<jats:p>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 '
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'represented the absorption, distribution, metabolism, and excretion of UDCA in each patient. '
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'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 '
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