Supplementary file 1_Clinical effects of ursodeoxycholic acid in COVID-19 infection: a systematic review and dose–response meta-analysis.docx

ObjectivesPrevious studies have shown that ursodeoxycholic acid (UDCA) reduces 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 for administration to prevent infection and relieve symptoms for COVID-19 infection, there are limited supporting studies with a high-level of evidence and recommendations for the exact dosage of UDCA. We conducted a systematic review and dose–response meta-analysis to evaluate the clinical effect of UDCA in COVID-19 infection.
MethodsStudies were identified through a literature search: PubMed, Embase, and Cochrane from inception to March 2025. We included research related to COVID-19 infection and UDCA. Primary outcomes were COVID-19 infection rate, mortality rate, COVID-19 severe infection risk, ventilator use, hospitalization, ICU hospitalization, and recovery time between UDCA group and controls. The 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. Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) was used to evaluate bias risk.
ResultsOf 188 articles, 15 cohort studies with 716,310 participants (control = 495,276; UDCA treatment = 221,034) were included. The level of risk of bias was seven studies at low, four at moderate, and four at serious. UDCA showed association with a lower risk of infection (OR, 0.69; 95% CI, 0.55–0.86), 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.
ConclusionThe findings support evidence for the clinical effects of UDCA for COVID-19 infection. There is a need for randomized trials to evaluate UDCA as a potential prophylactic agent against COVID-19.
Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251019195, identifier #CRD420251019195.