ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Infectious Diseases
Clinical effects of ursodeoxycholic acid in COVID-19 infection: A systematic review and dose-response meta-analysis
Joo Hye Song 1
Sung Ryul Shim 2
Jieun Shin 2
Won Hyeok Choe 1
Jiho Park 1
Tae Hee Lee 2
Seonghui Kang 2
Taeho Greg Rhee 3
Kyu Chan Huh 2
1. Konkuk University Medical Center, Gwangjin-gu, Republic of Korea
2. Konyang University, Nonsan-si, Republic of Korea
3. Yale University, New Haven, United States
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Abstract
ABSTRACT Objectives Previous studies showed that ursodeoxycholic acid reduced COVID-19 infection by inhibiting farnesoid X receptor activity, a direct regulator of ACE2. Even though UDCA, an easily accessible medication with few side effects, could be considered administration to prevent infection and relieve symptoms for COVID-19 infection, there are limited studies with high-level of evidence and recommendation for exact dosage of UDCA to support it. We conducted a systematic review and dose-response meta-analysis to evaluate clinical effect of UDCA in COVID-19 infection. Methods Studies were identified through literature search; PubMed, Embase, and Cochrane from inception inclusive March 2025. We included research related to COVID-19 infection and UDCA. The primary outcome was COVID-19 infection rate, mortality rate, COVID-19 severe infection risk, ventilator use, hospitalization, ICU hospitalization and recovery time between UDCA group and controls. And secondary outcome was UDCA dose-response association regarding infection risk. We analyzed for odds ratios (ORs) including infection rate, mortality rate, severe infection risk, ventilator use, hospitalization, and intensive care unit hospitalization, and for standardized mean difference (SMD) including recovery time between UDCA groups and controls. The Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) was used to evaluate the risk of bias. Results Among 188 articles, finally fifteen cohort studies with 716,310 participants (control=495,276, and UDCA treatment=221,034) were included. The level of risk of bias was 7 studies with low, 4 studies with moderate and 4 studies with serious. UDCA showed association with a lower risk of infection (OR,0.69;95%CI,0.55-0.86). And UDCA associated with lower severe infection risk (OR,0.75;95%CI,0.64-0.89), and ventilator use (OR,0.75;95%CI,0.62-0.90) compared to controls. Conclusion Findings support evidence for clinical effects of UDCA for COVID-19 infection. There is a need for randomized trials to evaluate UDCA as a potential
Summary
Keywords
COVID-19, dose response, Infection, Meta-analysis, Ursodeoxycholic Acid
Received
03 November 2025
Accepted
20 February 2026
Copyright
© 2026 Song, Shim, Shin, Choe, Park, Lee, Kang, Rhee and Huh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Kyu Chan Huh
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