Effect of Ursodeoxycholic Acid for Sars-Cov-2 Prevention in Hematological Malignancies: An Observational Real-World Study

{ 'indexed': {'date-parts': [[2023, 12, 2]], 'date-time': '2023-12-02T00:50:10Z', 'timestamp': 1701478210518}, 'reference-count': 0, 'publisher': 'American Society of Hematology', 'issue': 'Supplement 1', 'content-domain': {'domain': ['ashpublications.org'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2023, 11, 28]]}, 'abstract': '<jats:title />\n' ' <jats:p>Introduction:</jats:p>\n' ' <jats:p>Disease-2019 (COVID-19) pandemic is caused by severe acute respiratory ' 'syndrome coronavirus 2 (SARS-CoV-2).After the adjustments and optimizations of Chinese ' 'control strategies and policies for COVID-19 on December of 2022, clinical exposure increased ' 'rapidly.There are greater concerns for patients with hematological malignancies, particularly ' 'those who have undergone hematopoietic stem cell transplantation (HSCT).</jats:p>\n' ' <jats:p>One promising preventive measure that has recently gained attention is ' 'ursodeoxycholic acid (UDCA). This drug is mainly used to treat biliary tract disease and ' 'other hepatobiliary disorders, particularly primary biliary cholangitis (Hirschfield GM, et ' 'al. Gut 2018); and also has been widely used at a higher dosage to prevent sinusoidal ' 'obstruction syndrome/veno-occlusive disease (SOS/VOD) after HSCT in the clinical setting. ' 'Recently, Brevini et al. demonstrated that UDCA downregulated ACE2 expression by reducing ' 'farnesoid X receptor signaling, resulting in reduced SARS-Cov-2 infection (Brevini T, et al. ' 'Nature 2022), indicating that pharmacological prophylaxis using UDCA against COVID-19 in ' 'vulnerable groups was feasible, but the clinical data to support this practice is ' 'limited.</jats:p>\n' ' <jats:p>Therefore, we aim to present epidemiological data for Chinese patients ' 'with hematological malignancies during this epidemic wave, and investigate the protection ' 'effects offered by UDCA against COVID-19 in these patients.</jats:p>\n' ' <jats:p>Methods:</jats:p>\n' ' <jats:p>This investigation was a single-center, observational real-world ' 'study, and was granted by the ethics committee of the Institute of Hematology &amp; Blood ' 'Diseases [No. QTJ2023012-EC-1]. The transplant patients were included in the “NICHE-SKIRT” ' 'project (Cao Y, et al. Am J Hematol 2023). Informed consent for the acquisition and the use ' 'of patient samples was obtained.</jats:p>\n' ' <jats:p>Data for hospitalized patients at the Institute of Hematology &amp; ' 'Blood Diseases Hospital (Tianjin, China) was reviewed between December 2022 and January 2023. ' 'COVID 19 status was assessed using hospital-reported PCR and/or antigen tests for twice a ' 'week. We analyzed follow-up records up to 14th February 2023. The primary end-point was the ' 'rate of COVID -19 infection.</jats:p>\n' ' <jats:p>Results:</jats:p>\n' ' <jats:p>We enrolled 393 patients with a median age of 38 years old. At the ' 'cutoff date, 297 patients (75.6%) had confirmed COVID-19 infection (72.5% in the allo-HSCT ' 'cohort). Among the 273 evaluable patients, the majority (64.8%) had asymptomatic/mild ' 'disease. The severe/critical patients accounted for only 15.8%. Seven hospitalized patients ' 'had died from COVID-19 by the last follow-up date. The median period between COVID-19 ' 'diagnosis and death was 15 days (range: 2-32 days).</jats:p>\n' ' <jats:p>Lower proportion of CD3+CD4+T cells associated with more severe ' 'COVID-19 clinical spectrum (Asymptomatic/mild [n = 97] moderate [n = 46], adjusted P = 0.001; ' 'Asymptomatic/mild vs. severe/critical [n = 25], adjusted P = 0.036).</jats:p>\n' ' <jats:p>Among these patients, 163 received UDCA (UDCA group) while 230 did not ' '(non-UDCA group). The COVID-19 infection rate was lower in the UDCA group (69.9% vs. 79.6%; ' 'P= 0.039). However, patients in the UDCA group had a higher ECOG score and Charlson ' 'Comorbidity Index (Table 1), suggesting that they were more likely to have underlying health ' 'conditions. To account for this potential bias, we performed PSM, which confirmed that the ' 'UDCA group had a significantly lower rate of COVID-19 infection compared to the non-UDCA ' 'group (69.0% vs. 81.0%; P = 0.049) in the validated cohort.</jats:p>\n' ' <jats:p>Univariate logistic regression analysis showed that only UDCA ' 'administration was associated with COVID-19 infection (OR: 0.598; P = 0.029). To further ' 'investigate the effect of UDCA in specific populations, we carried out an exploratory ' 'analysis. Our results suggest that males, patients with a CCI ≥ 2, a history of smoking, and ' 'those with acute lymphoblastic leukemia (ALL) may benefit the most from the protective effect ' 'of UDCA against COVID-19.</jats:p>\n' ' <jats:p>Conclusion:</jats:p>\n' ' <jats:p>This study aimed to investigate the prevalence and clinical outcomes ' 'of SARS-CoV-2 infections in Chinese patients with hematologic disorders during the COVID-19 ' 'epidemic that began at the end of 2022. Our findings provide support for preclinical studies ' 'suggesting that UDCA may have marginal benefit in protecting against COVID-19. However, ' 'prospective studies with a higher dose of UDCA need to be performed.</jats:p>', 'DOI': '10.1182/blood-2023-182862', 'type': 'journal-article', 'created': {'date-parts': [[2023, 12, 1]], 'date-time': '2023-12-01T17:11:05Z', 'timestamp': 1701450665000}, 'page': '7308-7308', 'update-policy': 'http://dx.doi.org/10.1182/blood.2019cm0000', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Effect of Ursodeoxycholic Acid for Sars-Cov-2 Prevention in Hematological Malignancies: An ' 'Observational Real-World Study', 'prefix': '10.1182', 'volume': '142', 'author': [ { 'given': 'Hongye', 'family': 'Gao', 'sequence': 'first', 'affiliation': [ { 'name': '1Institute of Hematology & Blood Diseases Hospital, Chinese ' 'Academy of Medical Sciences & Peking Union Medical College, ' 'Tianjin, China'}]}, { 'given': 'Jiali', 'family': 'Wang', 'sequence': 'additional', 'affiliation': [ { 'name': '2State Key Laboratory of Experimental Hematology, National ' 'Clinical Research Center for Blood Diseases, Haihe Laboratory of ' 'Cell Ecosystem, Institute of Hematology & Blood Diseases ' 'Hospital, Chinese Academy of Medical Sciences &Peking Union ' 'Medical College, Tianjin, China'}]}, { 'given': 'Xinhui', 'family': 'Zheng', 'sequence': 'additional', 'affiliation': [ { 'name': '1Institute of Hematology & Blood Diseases Hospital, Chinese ' 'Academy of Medical Sciences & Peking Union Medical College, ' 'Tianjin, China'}]}, { 'given': 'Yigeng', 'family': 'Cao', 'sequence': 'additional', 'affiliation': [ { 'name': '2State Key Laboratory of Experimental Hematology, National ' 'Clinical Research Center for Blood Diseases, Haihe Laboratory of ' 'Cell Ecosystem, Institute of Hematology & Blood Diseases ' 'Hospital, Chinese Academy of Medical Sciences &Peking Union ' 'Medical College, Tianjin, China'}]}, { 'given': 'Erlie', 'family': 'Jiang', 'sequence': 'additional', 'affiliation': [ { 'name': '2State Key Laboratory of Experimental Hematology, National ' 'Clinical Research Center for Blood Diseases, Haihe Laboratory of ' 'Cell Ecosystem, Institute of Hematology & Blood Diseases ' 'Hospital, Chinese Academy of Medical Sciences &Peking Union ' 'Medical College, Tianjin, China'}]}], 'member': '234', 'container-title': 'Blood', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://ashpublications.org/blood/article/142/Supplement%201/7308/500982/Effect-of-Ursodeoxycholic-Acid-for-Sars-Cov-2', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'syndication'}, { 'URL': 'https://ashpublications.org/blood/article/142/Supplement%201/7308/500982/Effect-of-Ursodeoxycholic-Acid-for-Sars-Cov-2', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 12, 1]], 'date-time': '2023-12-01T17:56:53Z', 'timestamp': 1701453413000}, 'score': 1, 'resource': { 'primary': { 'URL': 'https://ashpublications.org/blood/article/142/Supplement%201/7308/500982/Effect-of-Ursodeoxycholic-Acid-for-Sars-Cov-2'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 28]]}, 'references-count': 0, 'journal-issue': {'issue': 'Supplement 1', 'published-print': {'date-parts': [[2023, 11, 28]]}}, 'URL': 'http://dx.doi.org/10.1182/blood-2023-182862', 'relation': {}, 'ISSN': ['0006-4971', '1528-0020'], 'subject': ['Cell Biology', 'Hematology', 'Immunology', 'Biochemistry'], 'published': {'date-parts': [[2023, 11, 28]]}}