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Vitamin D supplementation and COVID-19 risk: a population-based, cohort study

Oristrell et al., Journal of Endocrinological Investigation, doi:10.1007/s40618-021-01639-9
Jul 2021  
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Mortality -1% Improvement Relative Risk Mortality (b) 4% Case 1% Case (b) 5% Vitamin D for COVID-19  Oristrell et al.  Prophylaxis Is prophylaxis with vitamin D beneficial for COVID-19? Retrospective 404,109 patients in Spain No significant difference in outcomes seen c19early.org Oristrell et al., J. Endocrinological .., Jul 2021 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Retrospective study of cholecalciferol and calcitriol supplementation in Catalonia showing a small but significant lower risk of cases with cholecalciferol, but no significant difference for mortality, or for calcitriol supplementation. Significant benefit was found for cases, severity, and mortality in patients achieving serum vitamin D levels ≥30ng/ml.
This is the 41st of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
risk of death, 1.0% higher, RR 1.01, p = 0.91, calcifediol, univariate.
risk of death, 4.0% lower, RR 0.96, p = 0.37, cholecalciferol, univariate.
risk of case, 1.0% lower, RR 0.99, p = 0.65, NNT 3499, calcifediol, univariate.
risk of case, 5.0% lower, RR 0.95, p = 0.004, cholecalciferol, multivariate.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Oristrell et al., 17 Jul 2021, retrospective, population-based cohort, Spain, peer-reviewed, 8 authors, dosage varies (calcifediol).
This PaperVitamin DAll
Vitamin D supplementation and COVID-19 risk: a population-based, cohort study
J Oristrell, J C Oliva, E Casado, I Subirana, D Domínguez, A Toloba, A Balado, M Grau
Journal of Endocrinological Investigation, doi:10.1007/s40618-021-01639-9
Purpose To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population. Methods All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression. Results Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001). Conclusions In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.
Discussion In this large population-based cohort, we have compared COVID-19 outcomes in patients supplemented with cholecalciferol or calcifediol versus untreated matched controls, finding only a mild reduction in the risk of SARS-CoV2 infection (diagnosed clinically or by PCR) in patients supplemented with cholecalciferol, and a small reduction in Declarations Conflicts of interest The authors declare no conflict of interest. The Catalan Agency for Health Quality and Evaluation (AQUAS), a governmental office, offered a data analyst for extracting all the data necessary for the development of this project. They had no role in the design of the study, analyses, interpretation of data; in the writing of the manuscript, or in the decision to publish these results. Institutional review board statement This study was approved by the Institutional Ethics Committee of the Corporació Sanitària Parc Taulí-Universitat Autònoma Barcelona (Project number 2020588). Informed consent Not applicable. Patient and public involvement It was not appropriate or possible to involve patients or the public in the design, or conduct, or reporting, or dissemination plans of our research. Transparency statement The lead author (J. Oristrell) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported. No important aspects of the study have been omitted, and there were no significant discrepancies from the study as it was planned. Dissemination..
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Mol ' 'Endocrinol 27:2116–2125. https://doi.org/10.1210/me.2013-1146', 'journal-title': 'Mol Endocrinol'}, { 'key': '1639_CR36', 'doi-asserted-by': 'publisher', 'first-page': '617', 'DOI': '10.1136/thoraxjnl-2014-206680', 'volume': '70', 'author': 'RCA Dancer', 'year': '2015', 'unstructured': 'Dancer RCA, Parekh D, Lax S et al (2015) Vitamin D deficiency ' 'contributes directly to the acute respiratory distress syndrome (ARDS). ' 'Thorax 70:617–624. https://doi.org/10.1136/thoraxjnl-2014-206680', 'journal-title': 'Thorax'}, { 'key': '1639_CR37', 'doi-asserted-by': 'publisher', 'first-page': '7432', 'DOI': '10.3892/mmr.2017.7546', 'volume': '16', 'author': 'J Xu', 'year': '2017', 'unstructured': 'Xu J, Yang J, Chen J et al (2017) Vitamin D alleviates ' 'lipopolysaccharide-induced acute lung injury via regulation of the ' 'renin-angiotensin system. Mol Med Rep 16:7432–7438. 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J Pathol 204:587–593', 'journal-title': 'J Pathol'}, { 'key': '1639_CR42', 'doi-asserted-by': 'publisher', 'first-page': '1296', 'DOI': '10.1016/j.kint.2020.07.019', 'volume': '98', 'author': 'A Werion', 'year': '2020', 'unstructured': 'Werion A, Belkhir L, Perrot M, Schmit G, Aydin S, Chen Z et al (2020) ' 'SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule. ' 'Kidney Int 98:1296–1307', 'journal-title': 'Kidney Int'}, { 'key': '1639_CR43', 'doi-asserted-by': 'publisher', 'first-page': '1216', 'DOI': '10.3390/jcm10061216', 'volume': '10', 'author': 'Z Armaly', 'year': '2021', 'unstructured': 'Armaly Z, Kinaneh S, Skorecki K (2021) Renal manifestations of COVID-19: ' 'physiology and pathophysiology. J Clin Med 10:1216. ' 'https://doi.org/10.3390/jcm10061216', 'journal-title': 'J Clin Med'}], 'container-title': 'Journal of Endocrinological Investigation', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40618-021-01639-9.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s40618-021-01639-9/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s40618-021-01639-9.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 1, 7]], 'date-time': '2022-01-07T19:17:19Z', 'timestamp': 1641583039000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s40618-021-01639-9'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 7, 17]]}, 'references-count': 43, 'journal-issue': {'issue': '1', 'published-print': {'date-parts': [[2022, 1]]}}, 'alternative-id': ['1639'], 'URL': 'http://dx.doi.org/10.1007/s40618-021-01639-9', 'relation': {}, 'ISSN': ['1720-8386'], 'subject': ['Endocrinology', 'Endocrinology, Diabetes and Metabolism'], 'container-title-short': 'J Endocrinol Invest', 'published': {'date-parts': [[2021, 7, 17]]}, 'assertion': [ { 'value': '28 June 2021', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '12 July 2021', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '17 July 2021', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The authors declare no conflict of interest. The Catalan Agency for Health ' 'Quality and Evaluation (AQUAS), a governmental office, offered a data analyst ' 'for extracting all the data necessary for the development of this project. They ' 'had no role in the design of the study, analyses, interpretation of data; in ' 'the writing of the manuscript, or in the decision to publish these results.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflicts of interest'}}, { 'value': 'This study was approved by the Institutional Ethics Committee of the Corporació ' 'Sanitària Parc Taulí—Universitat Autònoma Barcelona (Project number 2020588).', 'order': 3, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Institutional review board statement'}}, { 'value': 'Not applicable.', 'order': 4, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Informed consent'}}, { 'value': 'It was not appropriate or possible to involve patients or the public in the ' 'design, or conduct, or reporting, or dissemination plans of our research.', 'order': 5, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Patient and public involvement'}}, { 'value': 'The lead author (J. Oristrell) affirms that the manuscript is an honest, ' 'accurate, and transparent account of the study being reported. No important ' 'aspects of the study have been omitted, and there were no significant ' 'discrepancies from the study as it was planned.', 'order': 6, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Transparency statement'}}, { 'value': 'Dissemination to the patients supplemented with vitamin D compounts is not ' 'applicable.', 'order': 7, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Dissemination declaration'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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