Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts
Giuseppe Marrone, Marcello Covino, Giuseppe Merra, Andrea Piccioni, Annamaria Amodeo, Angela Novelli, Rita Murri, Maurizio Pompili, Antonio Gasbarrini, Francesco Franceschi
Liver International, doi:10.1111/liv.15736
Background: Ursodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin-converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID-19.
Aim and Study Design: We retrospectively evaluated the clinical course and outcome of subjects taking UDCA admitted to the hospital for COVID-19 compared with matched infected subjects. Differences regarding the severity and outcome of the disease between treated and non-treated subjects were assessed. The Kaplan-Meier survival analysis and log-rank test were used to evaluate the effect of UDCA on allcause intra-hospital mortality. Results: Among 6444 subjects with confirmed COVID-19 admitted to the emergency department (ED) from 1 March 2020 to 31 December 2022, 109 subjects were taking UDCA. After matching 629 subjects were included in the study: 521 in the no UDCA group and 108 in the UDCA group. In our matched cohort, 144 subjects (22.9%) died, 118 (22.6%) in the no-UDCA group and 26 (24.1%) in the UDCA group. The Kaplan-Meier analysis showed no significant difference in survival between groups. In univariate regression analysis, the presence of pneumonia, National Early Warning Score (NEWS) score, and Charlson Comorbidity Index (CCI) were significant independent predictors of death. At multivariate Cox regression analysis, age, NEWS, pneumonia and CCI index were confirmed significant independent predictors of death. UDCA treatment was not a predictor of survival both in univariate and multivariate regressions. Conclusions: UDCA treatment does not appear to have significant effects on the outcome of COVID-19. Specially designed prospective studies are needed to evaluate efficacy in preventing infection and severe disease.
K E Y W O R D S COVID-19, SARS-CoV-2, UDCA
Key points Treatment with ursodeoxycholic acid has no effect on the outcome of SARS-CoV-2 infection in hospitalized subjects. Age, presence of pneumonia, comorbidities and severity at onset are confirmed as predictors of unfavourable outcomes.
AUTH O R CO NTR I B UTI O N S Marcello Covino and Giuseppe Marrone were responsible for the conception and writing of the paper; Marcello Covino, Annamaria Amodeo and Giuseppe Marrone performed data collection, Marcello Covino and Giuseppe Marrone performed data analysis, Maurizio Pompili, Rita Murri, Angela Novelli, Andrea Piccioni and Giuseppe Merra reviewed the manuscript; Francesco Franceschi, Antonio Gasbarrini, Marcello Covino, Giuseppe Marrone performed final editing of the manuscript. All the authors approved the final version of the manuscript.
CO N FLI C T O F I NTER E S T S TATEM ENT The authors do not have any disclosures to report.
S U PP O RTI N G I N FO R M ATI O N Additional supporting information can be found online in the Supporting Information section at the end of this article.
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References
Alenezi, Almeshari, Mahida, Bangash, Thickett et al., Incidence and risk factors of acute kidney injury in COVID-19 patients with and without acute respiratory distress syndrome (ARDS) during the first wave of COVID-19: a systematic review and meta-analysis, Ren Fail,
doi:/10.1080/0886022X.2021.2011747Biswas, Rahaman, Biswas, Haque, Association of sex, age, and comorbidities with mortality in COVID-19 patients: a systematic review and meta-analysis, Intervirology,
doi:/10.1159/000512592Canales, Mayoral, Hernández-Huerta, Interaction of spike protein and lipid membrane of SARS-CoV-2 with Ursodeoxycholic acid, an in-silico analysis, Sci Rep,
doi:/10.1038/S41598-021-01705-5Carino, Moraca, Fiorillo, Hijacking SARS-CoV-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on the receptor binding domain, Front Chem,
doi:/10.3389/FCHEM.2020.572885/BIBTEXCharlson, Pompei, Ales, Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation, J Chronic Dis,
doi:/10.1016/0021-9681(87)90171-8Charlton, Levitsky, Aqel, International liver transplant society consensus statement on immunosuppression in liver transplant recipients, Transplantation,
doi:/10.1097/TP.0000000000002147Cheung, Mok, Mao, COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: a meta-analysis, Clin Mol Hepatol,
doi:/10.3350/CMH.2022.0087Colapietro, Angelotti, Masetti, Ursodeoxycholic acid does not improve COVID-19 outcome in hospitalized patients, Viruses,
doi:/10.3390/v15081738Covino, Petruzziello, Onder, A 12-year retrospective analysis of differences between elderly and oldest old patients referred to the emergency department of a large tertiary hospital, Maturitas,
doi:/10.1016/J.MATURITAS.2018.11.011Covino, Russo, Salini, Frailty assessment in the emergency department for risk stratification of COVID-19 patients aged ≥80 years, J Am Med Dir Assoc,
doi:/10.1016/J.JAMDA.2021.07.005Cromer, Steain, Reynaldi, Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis, Nat Commun,
doi:/10.1038/S41467-023-37176-7De Almeida, Borges Freire, De Andrade, The landscape of neutralizing monoclonal antibodies (nAbs) for treatment and prevention of COVID-19, J Pharm Innov,
doi:/10.1007/S12247-023-09713-WGiovinazzo, Vaccaro, Pascale, SARS-CoV-2 infection in adult liver transplantation recipients: a systematic review of risk factors for mortality and immunosuppression role, Eur Rev Med Pharmacol Sci,
doi:/10.26355/eurrev_202302_31413Gottlieb, Vaca, Paredes, Early Remdesivir to prevent progression to severe Covid-19 in outpatients, N Engl J Med,
doi:/10.1056/NEJMOA2116846Grieco, Menga, Cesarano, Effect of helmet noninvasive ventilation vs high-flow nasal oxygen on days free of respiratory support in patients with COVID-19 and moderate to severe hypoxemic respiratory failure: the HENIVOT randomized clinical trial, JAMA,
doi:/10.1001/JAMA.2021.4682Grupper, Rabinowich, Schwartz, Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus, Am J Transplant,
doi:/10.1111/AJT.16615Hirschfield, Beuers, Corpechot, EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis, J Hepatol,
doi:/10.1016/J.JHEP.2017.03.022Hoffmann, Kleine-Weber, Schroeder, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell,
doi:/10.1016/J.CELL.2020.02.052Horby, Mafham, Bell, Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial, Lancet,
doi:/10.1016/S0140-6736(20)32013-4Işık, Karaman, Micili, Beneficial effects of ursodeoxycholic acid via inhibition of airway remodelling, apoptosis of airway epithelial cells, and Th2 immune response in murine model of chronic asthma, Allergol Immunopathol,
doi:/10.1016/J.ALLER.2016.12.003John, Bastaich, Webb, Ursodeoxycholic acid is associated with a reduction in SARS-CoV-2 infection and reduced severity of COVID-19 in patients with cirrhosis, J Intern Med,
doi:/10.1111/JOIM.13630Li, Li, Chang, Liu, High-flow nasal cannula reduces intubation rate in patients with COVID-19 with acute respiratory failure: a meta-analysis and systematic review, BMJ Open,
doi:/10.1136/BMJOPEN-2022-067879Li, Noreen, Zhang, A critical analysis of SARS-CoV-2 (COVID-19) complexities, emerging variants, and therapeutic interventions and vaccination strategies, Biomed Pharmacother,
doi:/10.1016/J.BIOPHA.2021.112550Marjot, Moon, Cook, Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study, J Hepatol,
doi:/10.1016/J.JHEP.2020.09.024Mcconnell, Harte, Walsh, Comparative effectiveness of neutralising monoclonal antibodies in high risk COVID-19 patients: a Bayesian network meta-analysis, Sci Rep,
doi:/10.1038/S41598-022-22431-6Mroz, Harvey, Ursodeoxycholic acid inhibits ENaC and Na/K pump activity to restore airway surface liquid height in cystic fibrosis bronchial epithelial cells, Steroids,
doi:/10.1016/J.STEROIDS.2019.108461Niu, Li, Xu, Sun, Gan et al., Ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome, J Cell Mol Med,
doi:/10.1111/JCMM.15985Ridjab, Ivan, Budiman, Juzar, Outcome in early vs late intubation among COVID-19 patients with acute respiratory distress syndrome: an updated systematic review and meta-analysis, Sci Rep,
doi:/10.1038/S41598-022-26234-7Rubin, Chan-Tack, Farley, Sherwat, FDA approval of remdesivir -a step in the right direction, N Engl J Med,
doi:/10.1056/NEJMP2032369Smith, Prytherch, Meredith, Schmidt, Featherstone, The ability of the National Early Warning Score (NEWS) to discriminate patients at risk of early cardiac arrest, unanticipated intensive care unit admission, and death, Resuscitation,
doi:/10.1016/J.RESUSCITATION.2012.12.016Sánchez-Zapardiel, Alós, Nozal, Humoral and cellular immune responses to Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine in adolescents with liver transplantation: single center experience, Front Immunol,
doi:/10.3389/FIMMU.2022.1049188Thuy, Bao, Moon, Ursodeoxycholic acid ameliorates cell migration retarded by the SARS-CoV-2 spike protein in BEAS-2B human bronchial epithelial cells, Biomed Pharmacother,
doi:/10.1016/J.BIOPHA.2022.113021Vardavas, Mathioudakis, Nikitara, Prognostic factors for mortality, intensive care unit and hospital admission due to SARS-CoV-2: a systematic review and meta-analysis of cohort studies in Europe, Eur Respir Rev,
doi:/10.1183/16000617.0098-2022Wang, Qiu, Liu, Wang, Zhao, The liver injury and gastrointestinal symptoms in patients with coronavirus disease 19: a systematic review and meta-analysis, Clin Res Hepatol Gastroenterol,
doi:/10.1016/J.CLINRE.2020.04.012Webb, Marjot, Cook, Outcomes following SARS-CoV-2 infection in liver transplant recipients: an international registry study, Lancet Gastroenterol Hepatol,
doi:/10.1016/S2468-1253(20)30271-5Xie, Wang, Liao, Marley, Wu et al., Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: systematic review and meta-analysis, BMC Infect Dis,
doi:/10.1186/S12879-020-05371-2
