Ursodeoxycholic acid for coronavirus disease 2019 prevention

Abstract: Research Letter doi: 10.1111/joim.13704 Ursodeoxycholic acid for coronavirus disease 2019 prevention Dear Editor, The novel coronavirus disease 2019 (COVID-19) has had a tremendous impact worldwide [1]. Although the management of COVID-19 has improved, the chemoprevention of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection remains a challenge. In 2022, the potential of ursodeoxycholic acid (UDCA) against COVID-19 was first reported [2]. Furthermore, the association of UDCA with a decrease in SARS-CoV-2 infection and reduction in symptomatic COVID-19 was retrospectively demonstrated [3]. These reports suggested the utility of UDCA in preventing COVID-19. However, the Omicron variant—predominant since early 2022— causes milder disease, including asymptomatic infection, compared to previously predominant variants [4]. If the infected patients had no or mild symptoms, they might not have tested for COVID-19; therefore, they might be unaware of their infection. A more objective evaluation of infection proportions in a cross-sectional cohort is needed to accurately evaluate the preventive ability. Here, we cross-sectionally examined the impact of UDCA on SARS-CoV-2 infection in early 2023. The infection was defined based on medical interviews and SARS-CoV-2 immunoglobulin G against the nucleocapsid protein (IgG-N), which could detect the previous SARS-CoV-2 infection regardless of vaccination [5]. The cutoff value for IgG-N was set at 5 AU/mL [6], which identifies infections for approximately 1 year (unpublished data), covering the Omicron variant–dominant period in Japan. Subclinical infection was defined as IgG-N positivity without interview-based infection. Outpatients attending the Department of Gastroenterology at The University of Tokyo Hospital between January 1, 2023, and February 10, 2023, were included (Fig. S1). The UDCA treatment group was compared with patients without a history of UDCA prescription (non-UDCA group) and patients with viral hepatitis without a history of UDCA prescription (non-UDCA viral hepatitis group). Age, sex, and the number of vaccinations were matched using propensity score-matching (PSM) analysis (nearest-neighbor matching at a ratio of 1:1 was performed using a caliper of 0.1). The study protocol was approved by the Research Ethics Committee of the Faculty of Medicine at the University of Tokyo (approval number:2019300NI4-(3)). Informed consent was obtained through an opt-out form. In the entire cohort, the SARS-CoV-2 infection proportion was not significantly different between the UDCA and non-UDCA groups (Fig. 1A and Table S1). The UDCA group tended to be older and had a higher proportion of women, while the vaccination status was similar. After PSM, there was no difference in the SARS-CoV-2 infection proportion between the two groups; however, the subclinical infection proportion tended to be higher in the UDCA group than non-UDCA group (Fig. 1B and Table S1). Between the UDCA and non-UDCA viral hepatitis groups, the SARS-CoV-2 infection proportion was not significantly different in the entire cohort (Fig. 1A and Table S2). Background factors were similar, except the proportion of women was higher in the UDCA group. After PSM, there was no difference in the SARS-CoV-2 infection proportion between the two groups; however, the subclinical infection proportion tended to be higher in the UDCA group than in the non-UDCA viral hepatitis group (Fig. 1C and Table S2). In this..