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Associations between predicted vitamin D status, vitamin D intake, and risk of SARS-CoV-2 infection and Coronavirus Disease 2019 severity

Ma et al., The American Journal of Clinical Nutrition, doi:10.1093/ajcn/nqab389
Dec 2021  
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Hospitalization 49% treatment Improvement Relative Risk Symp. case -7% treatment Case 17% treatment Hospitalization (b) 67% levels Symp. case (b) 9% levels Case (b) 52% levels Vitamin D for COVID-19  Ma et al.  Prophylaxis Is prophylaxis with vitamin D beneficial for COVID-19? Retrospective 39,315 patients in the USA (May 2020 - March 2021) Lower hospitalization with vitamin D (p=0.04) c19early.org Ma et al., The American J. Clinical Nu.., Dec 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
Analysis of 39,915 patients with 1,768 COVID+ cases based on surveys in the Nurses' Health Study II, showing higher predicted vitamin D levels associated with lower risk of COVID-19 cases. There was significantly lower risk of hospitalization with vitamin D supplementation (≥400 IU/d), but no significant differences for cases based on supplementation.
This is the 60th 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.
Study covers sunlight and vitamin D.
risk of hospitalization, 49.0% lower, OR 0.51, p = 0.04, treatment 26,605, control 12,710, adjusted per study, supplementation ≥400 IU/day, model 3, supplemental table 3, multivariable, RR approximated with OR.
risk of symptomatic case, 7.0% higher, OR 1.07, p = 0.25, treatment 7,895, control 31,420, adjusted per study, supplementation ≥2000 IU/day vs. <400 IU/day, model 3, supplemental table 3, multivariable, RR approximated with OR.
risk of case, 17.0% lower, OR 0.83, p = 0.07, treatment 7,895, control 31,420, adjusted per study, supplementation ≥2000 IU/day vs. <400 IU/day, model 3, supplemental table 3, multivariable, RR approximated with OR.
risk of hospitalization, 67.0% lower, OR 0.33, p = 0.15, high D levels 7,893, low D levels 7,823, adjusted per study, highest quintile vs. lowest quintile predicted vitamin D levels, model 3, supplemental table 3, multivariable, RR approximated with OR, outcome based on serum levels.
risk of symptomatic case, 9.0% lower, OR 0.91, p = 0.52, high D levels 7,893, low D levels 7,823, adjusted per study, highest quintile vs. lowest quintile predicted vitamin D levels, model 3, supplemental table 3, multivariable, RR approximated with OR, outcome based on serum levels.
risk of case, 52.0% lower, OR 0.48, p = 0.01, high D levels 7,893, low D levels 7,823, adjusted per study, highest quintile vs. lowest quintile predicted vitamin D levels, model 3, supplemental table 3, multivariable, RR approximated with OR, outcome based on serum levels.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ma et al., 3 Dec 2021, retrospective, USA, peer-reviewed, 16 authors, study period May 2020 - March 2021, dosage varies. Contact: achan@mgh.harvard.edu.
This PaperVitamin DAll
Associations between predicted vitamin D status, vitamin D intake, and risk of SARS-CoV-2 infection and Coronavirus Disease 2019 severity
ScD Wenjie Ma, MD Long H Nguyen, MS Yiyang Yue, ScD Ming Ding, PhD David A Drew, MD, PhD Kai Wang, PhD Jordi Merino, ScD Janet W Rich-Edwards, MD, ScD Qi Sun, MD, DrPH Carlos A Camargo Jr, MD, ScD Edward Giovannucci, MD, DrPH Walter Willett, MD, DrPH Joann E Manson, MD, ScD Mingyang Song, PhD Shilpa N Bhupathiraju, MD, MPH Andrew T Chan
doi:10.1093/ajcn/nqab389/6448988
Background: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) severity have been limited and inconsistent. Objective: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity. Design: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1,768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semi-quantitative, pre-pandemic food frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] levels were calculated based on a previously validated model including dietary and supplementary vitamin D intake, ultraviolet-B (UVB), and other behavioral predictors of vitamin D status. Results: Higher predicted 25(OH)D levels, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D levels to the lowest, the multivariable-adjusted odds ratio was 0.76 (95% CI: 0.58, 0.99; P-trend=0.04). Participants in the highest quartile of UVB (OR: 0.76; 95% CI: 0.66, 0.87; P-trend=0.002) and UVA (OR: 0.76; 95% CI: 0.66, 0.88; P-trend<0.001) also had lower risk of SARS-CoV-2 infection compared
93 Logistic regression models were used in the analysis. The number of participants included in the analysis was 39,315, and the number of participants who reported a positive SARS-CoV-2 infection was 1,768. Model 1 was adjusted for age, white race, smoking pack-years (0, 0.1-10.0, 10.1-20.0, >20.0), and the Alternate Healthy Eating Index (quintiles). Vitamin D intakes from foods and supplements were mutually adjusted. Model 2 was further adjusted for body mass index (<22.5, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30-34.9, ≥35.0 kg/m 2 ), physical activity (quintiles), and alcohol intake (0, 0.1-5.0, 5.1-10.0, >10 g/d). Model 3 was further adjusted for being a frontline healthcare worker, chronic comorbidities including hypertension, hypercholesterolemia, diabetes, heart disease, cancer, and asthma, and 2010 census tract median income (quintiles). P-trend was evaluated using the median value in each category as a continuous variable. Abbreviations: 25(OH)D, 25-hydroxyvitamin D. .001 Logistic regression models were used in the analysis. The number of participants included in the analysis was 39,315, and the number of participants who reported a positive SARS-CoV-2 infection was 1,768. Model 1 was adjusted for age, white race, smoking pack-years (0, 0.1-10.0, 10.1-20.0, >20.0), and the Alternate Healthy Eating Index (quintiles). Model 2 was further adjusted for body mass index (<22.5, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30-34.9, ≥35.0 kg/m 2 ), physical activity..
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{ 'indexed': {'date-parts': [[2021, 12, 6]], 'date-time': '2021-12-06T05:49:49Z', 'timestamp': 1638769789018}, 'reference-count': 0, 'publisher': 'Oxford University Press (OUP)', 'license': [ { 'start': { 'date-parts': [[2021, 12, 3]], 'date-time': '2021-12-03T00:00:00Z', 'timestamp': 1638489600000}, 'content-version': 'am', 'delay-in-days': 0, 'URL': 'https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'short-container-title': [], 'abstract': '<jats:title>Abstract</jats:title>\n' ' <jats:sec>\n' ' <jats:title>Background</jats:title>\n' ' <jats:p>Vitamin D may have a role in immune responses to viral infections. ' 'However, data on the association between vitamin D and SARS-CoV-2 infection and Coronavirus ' 'Disease 2019 (COVID-19) severity have been limited and inconsistent.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Objective</jats:title>\n' ' <jats:p>We examined the associations of predicted vitamin D status and ' 'intake with risk of SARS-CoV-2 infection and COVID-19 severity.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Design</jats:title>\n' ' <jats:p>We used data from periodic surveys (May 2020 to March 2021) within ' 'the Nurses’ Health Study II. Among 39,315 participants, 1,768 reported a positive test for ' 'SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a ' 'semi-quantitative, pre-pandemic food frequency questionnaire in 2015. Predicted ' '25-hydroxyvitamin D [25(OH)D] levels were calculated based on a previously validated model ' 'including dietary and supplementary vitamin D intake, ultraviolet-B (UVB), and other ' 'behavioral predictors of vitamin D status.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results</jats:title>\n' ' <jats:p>Higher predicted 25(OH)D levels, but not vitamin D intake, were ' 'associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest ' 'quintile of predicted 25(OH)D levels to the lowest, the multivariable-adjusted odds ratio was ' '0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UVB (OR: ' '0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UVA (OR: 0.76; 95% CI: 0.66, 0.88; ' 'P-trend&amp;lt;0.001) also had lower risk of SARS-CoV-2 infection compared to the lowest. ' 'High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of ' 'hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04).</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusions</jats:title>\n' ' <jats:p>Our study provides suggestive evidence on the association between ' 'higher predicted circulating 25(OH)D levels and a lower risk of SARS-CoV-2 infection. Greater ' 'intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data ' 'also support an association between exposure to UVB or UVA, independent of vitamin D, and ' 'SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted ' 'cautiously.</jats:p>\n' ' </jats:sec>', 'DOI': '10.1093/ajcn/nqab389', 'type': 'journal-article', 'created': { 'date-parts': [[2021, 11, 22]], 'date-time': '2021-11-22T12:06:50Z', 'timestamp': 1637582810000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': [ 'Associations between predicted vitamin D status, vitamin D intake, and risk of SARS-CoV-2 ' 'infection and Coronavirus Disease 2019 severity'], 'prefix': '10.1093', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-9894-7072', 'authenticated-orcid': False, 'given': 'Wenjie', 'family': 'Ma', 'sequence': 'first', 'affiliation': [ { 'name': 'Clinical and Translational Epidemiology Unit, Massachusetts ' 'General Hospital and Harvard Medical School, Boston, MA'}, { 'name': 'Division of Gastroenterology, Massachusetts General Hospital and ' 'Harvard Medical School, Boston, MA'}]}, { 'given': 'Long H', 'family': 'Nguyen', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical and Translational Epidemiology Unit, Massachusetts ' 'General Hospital and Harvard Medical School, Boston, MA'}, { 'name': 'Division of Gastroenterology, Massachusetts General Hospital and ' 'Harvard Medical School, Boston, MA'}]}, { 'ORCID': 'http://orcid.org/0000-0002-6018-2980', 'authenticated-orcid': False, 'given': 'Yiyang', 'family': 'Yue', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Nutrition, Harvard T.H. 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Chan School of Public ' 'Health, Boston, MA'}, { 'name': 'Division of Preventive Medicine, Department of Medicine, Brigham ' "and Women's Hospital and Harvard Medical School, Boston, MA"}]}, { 'ORCID': 'http://orcid.org/0000-0002-4780-4642', 'authenticated-orcid': False, 'given': 'Mingyang', 'family': 'Song', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical and Translational Epidemiology Unit, Massachusetts ' 'General Hospital and Harvard Medical School, Boston, MA'}, { 'name': 'Division of Gastroenterology, Massachusetts General Hospital and ' 'Harvard Medical School, Boston, MA'}, { 'name': 'Department of Nutrition, Harvard T.H. Chan School of Public ' 'Health, Boston, MA'}, { 'name': 'Department of Epidemiology, Harvard T.H. Chan School of Public ' 'Health, Boston, MA'}]}, { 'given': 'Shilpa N', 'family': 'Bhupathiraju', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Nutrition, Harvard T.H. Chan School of Public ' 'Health, Boston, MA'}, { 'name': 'Channing Division of Network Medicine, Department of Medicine, ' "Brigham and Women's Hospital and Harvard Medical School, Boston, " 'MA'}]}, { 'ORCID': 'http://orcid.org/0000-0001-7284-6767', 'authenticated-orcid': False, 'given': 'Andrew T', 'family': 'Chan', 'sequence': 'additional', 'affiliation': [ { 'name': 'Clinical and Translational Epidemiology Unit, Massachusetts ' 'General Hospital and Harvard Medical School, Boston, MA'}, { 'name': 'Division of Gastroenterology, Massachusetts General Hospital and ' 'Harvard Medical School, Boston, MA'}, { 'name': 'Department of Epidemiology, Harvard T.H. Chan School of Public ' 'Health, Boston, MA'}, { 'name': 'Channing Division of Network Medicine, Department of Medicine, ' "Brigham and Women's Hospital and Harvard Medical School, Boston, " 'MA'}]}], 'member': '286', 'published-online': {'date-parts': [[2021, 12, 3]]}, 'container-title': ['The American Journal of Clinical Nutrition'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://academic.oup.com/ajcn/advance-article-pdf/doi/10.1093/ajcn/nqab389/41505202/nqab389.pdf', 'content-type': 'application/pdf', 'content-version': 'am', 'intended-application': 'syndication'}, { 'URL': 'https://academic.oup.com/ajcn/advance-article-pdf/doi/10.1093/ajcn/nqab389/41505202/nqab389.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 12, 5]], 'date-time': '2021-12-05T09:08:09Z', 'timestamp': 1638695289000}, 'score': 1, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 12, 3]]}, 'references-count': 0, 'URL': 'http://dx.doi.org/10.1093/ajcn/nqab389', 'relation': {}, 'ISSN': ['0002-9165', '1938-3207'], 'issn-type': [{'value': '0002-9165', 'type': 'print'}, {'value': '1938-3207', 'type': 'electronic'}], 'subject': ['Nutrition and Dietetics', 'Medicine (miscellaneous)'], 'published': {'date-parts': [[2021, 12, 3]]}}
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