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Objective: This study aimed to assess the chemopreventive effect of ursodeoxycholic acid (UDCA) against COVID-19 and to analyze infection risk factors, symptoms, and recovery in outpatients with UDCA exposure.Methods: The study enrolled outpatients prescribed UDCA from the Second Affiliated Hospital of Chongqing Medical University, China, between 01 July 2022, and 31 December 2022. Data on demographics, comorbidities, and drug combinations were collected using electronic medical records. COVID-19 infection, symptoms, severity, prognosis, vaccinations, and UDCA administration were surveyed by telephone interviews. UDCA non-users served as controls and were matched in a 1:2 ratio with UDCA users using propensity score matching with the nearest neighbor algorithm. Infection rates, symptomatology, severity, and prognosis were compared between matched and control cohorts, and risk factors and infection and recovery symptoms were analyzed in UDCA-exposed outpatients.Results: UDCA-exposed outpatients (n = 778, 74.8%) and matched UDCA users (n = 95, 74.2%) showed significantly lower SARS-CoV-2 infection rates than control patients (n = 59, 92.2%) (p < 0.05). The matched UDCA group exhibited substantially lower fever, cough, sore throat, and fatigue rates than controls (p < 0.05). Participants with UDCA exposure generally experienced mild symptoms, while those without UDCA had moderate symptoms. The matched UDCA group also had significantly shorter durations of fever and cough (p < 0.05). Risk factors such as age over 60, less than 1 month of UDCA administration, diabetes mellitus, and coronary artery disease significantly increased SARS-CoV-2 infection rates (p < 0.05), while smoking led to a decrease (p < 0.05). Hypertension was associated with a prolonged COVID-19 recovery (p < 0.05), while smoking, vaccination, and fatty liver disease were associated with shorter recovery periods (p < 0.05). The main symptoms in the full UDCA cohort were fever, cough, and sore throat, with fatigue, cough, and hyposthenia being the most persistent.Conclusion: UDCA demonstrated chemopreventive effect against SARS-CoV-2 in outpatients by significantly reducing infection incidence and mitigating COVID-19 symptoms, severity, and recovery duration. Old age, short UDCA course, and comorbidities such as diabetes mellitus and CAD increased infection rates, while hypertension prolonged recovery. Smoking, vaccination, and fatty liver disease reduced infection rates and shortened recovery. UDCA had minimal impact on symptom types. Larger and longer-term clinical studies are needed further to assess UDCA’s effectiveness in COVID-19 prevention or treatment.

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.