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Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study

Wang et al., BMC Pulmonary Medicine, doi:10.1186/s12890-024-03013-w
Apr 2024  
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Severe case 35% per SD Improvement Relative Risk Hospitalization 24% per SD Case 31% per SD Vitamin A for COVID-19  Wang et al.  Prophylaxis Is vitamin A associated with COVID-19 outcomes? Mendelian randomization study in multiple countries Fewer cases with higher vitamin A (p=0.006) c19early.org Wang et al., BMC Pulmonary Medicine, Apr 2024 Favorsvitamin A Favorscontrol 0 0.5 1 1.5 2+
Vitamin A for COVID-19
42nd treatment shown to reduce risk in June 2023, now with p = 0.021 from 14 studies.
Lower risk for recovery and cases.
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Mendelian randomization study suggesting a causal association between retinol and related proteins (RBP4, RDH16, CRABP1) and COVID-19. The study found that genetically-predicted higher retinol levels were associated with lower COVID-19 susceptibility. There was a lower risk of hospitalization and severity without statistical significance. Authors conclude that the results support a potential protective effect of vitamin A treatment for COVID-19. Given the lack of clear evidence for pleiotropy, and the lower precision of the MR-Egger estimates, the IVW estimates are likely more reliable in this case when the IVW and MR-Egger estimates differ.
risk of severe case, 35.0% lower, OR 0.65, p = 0.28, IVW, RR approximated with OR.
risk of hospitalization, 24.0% lower, OR 0.76, p = 0.29, IVW, RR approximated with OR.
risk of case, 31.0% lower, OR 0.69, p = 0.006, IVW, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Wang et al., 26 Apr 2024, retrospective, multiple countries, peer-reviewed, 6 authors, Mendelian - per SD. Contact: shuishui286@qq.com, xsp1984211@163.com.
This PaperVitamin AAll
Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study
Haixia Wang, Zhiyun Zhang, Li Xie, Kongli Lu, Shuyi Zhang, Shunpeng Xing
BMC Pulmonary Medicine, doi:10.1186/s12890-024-03013-w
Background The Corona Virus Disease 2019 (COVID-19) pandemic has struck globally. Whether the related proteins of retinoic acid (RA) signaling pathway are causally associated with the risk of COVID-19 remains unestablished. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of retinol, retinol binding protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein 1 (CRABP1) with COVID-19 in European population. Methods The outcome utilized the summary statistics of COVID-19 from the COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the causal relationship between exposure and outcome. Sensitivity analyses were performed to ensure the validity of the results. Results The MR estimates showed that retinol was associated with lower COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53-0.90, P: 0.0065), whereas the associations between retinol and COVID-19 hospitalization or severity were not significant. RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% CI: 0.72-0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 hospitalization (OR: 1.10, 95% CI: 1.01-1.18, P: 0.0199). CRABP1 was association with lower COVID-19 susceptibility (OR: 0.95, 95% CI: 0.91-0.99, P: 0.0290) using the IVW. Conclusions We found evidence of possible causal association of retinol, RBP4, RDH16 and CRABP1 with the susceptibility, hospitalization and severity of COVID-19. Our study defines that retinol is significantly associated with lower COVID-19 susceptibility, which provides a reference for the prevention of COVID-19 with vitamin A supplementation.
Supplementary Information The online version contains supplementary material available at https://doi. org/10.1186/s12890-024-03013-w. Supplementary Material 1 Supplementary Material 2 Author contributions HW and ZZ: data collection and statistical analysis, LX: statistical analysis and manuscript revision, HW, ZZ and KL: manuscript preparation,SZ and SX: study design and supervision, all authors: manuscript revision. All authors contributed to the article and approved the submitted version. Declarations Ethical approval and informed consent Not applicable. Consent to publish Not applicable. Competing interests The authors have no relevant financial or non-financial interests to disclose. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Whether the related proteins of retinoic acid (RA) signaling pathway are causally ' 'associated with the risk of COVID-19 remains unestablished. We conducted a two-sample ' 'Mendelian randomization (MR) study to assess the associations of retinol, retinol binding ' 'protein 4 (RBP4), retinol dehydrogenase 16 (RDH16) and cellular retinoic acid binding protein ' '1 (CRABP1) with COVID-19 in European population.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Methods</jats:title>\n' ' <jats:p>The outcome utilized the summary statistics of COVID-19 from the ' 'COVID-19 Host Genetics Initiative. The exposure data were obtained from public genome wide ' 'association study (GWAS) database. We extracted SNPs from exposure data and outcome data. The ' 'inverse variance weighted (IVW), MR-Egger and Wald ratio methods were employed to assess the ' 'causal relationship between exposure and outcome. Sensitivity analyses were performed to ' 'ensure the validity of the results.</jats:p>\n' ' </jats:sec><jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>The MR estimates showed that retinol was associated with lower ' 'COVID-19 susceptibility using IVW (OR: 0.69, 95% CI: 0.53–0.90, P: 0.0065), whereas the ' 'associations between retinol and COVID-19 hospitalization or severity were not significant. ' 'RBP4 was associated with lower COVID-19 susceptibility using the Wald ratio (OR: 0.83, 95% ' 'CI: 0.72–0.95, P: 0.0072). IVW analysis showed RDH16 was associated with increased COVID-19 ' 'hospitalization (OR: 1.10, 95% CI: 1.01–1.18, P: 0.0199). 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' 'Angewandte Chemie (International ed in English). 2021;60(13):7098–110.', 'DOI': '10.1002/anie.202015639'}, { 'key': '3013_CR31', 'doi-asserted-by': 'publisher', 'first-page': '659977', 'DOI': '10.3389/fphys.2021.659977', 'volume': '12', 'author': 'JS Steinhoff', 'year': '2021', 'unstructured': 'Steinhoff JS, Lass A, Schupp M. Biological functions of RBP4 and its ' 'relevance for Human diseases. Front Physiol. 2021;12:659977.', 'journal-title': 'Front Physiol'}, { 'issue': '2', 'key': '3013_CR32', 'doi-asserted-by': 'publisher', 'first-page': '197', 'DOI': '10.3945/an.116.014167', 'volume': '8', 'author': 'LP Rubin', 'year': '2017', 'unstructured': 'Rubin LP, Ross AC, Stephensen CB, Bohn T, Tanumihardjo SA. Metabolic ' 'effects of inflammation on vitamin A and carotenoids in humans and ' 'animal models. 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