Exploring the association between vitamin D status and Corona Virus-19 infection in a cohort of adults aged 50 years and older
et al., Clinical Nutrition Open Science, doi:10.1016/j.nutos.2025.05.007, NCT04482673, May 2025
Vitamin D for COVID-19
8th treatment shown to reduce risk in
October 2020, now with p < 0.00000000001 from 126 studies, recognized in 18 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
Prospective study of 131 adults aged 50+ years showing lower vitamin D status was significantly associated with higher risk of COVID-19 infection and hospitalization. Adjusted results based on deficiency are only provided for cases (other adjusted results only use continuous values for vitamin D levels).
This is the 218th of 226 COVID-19 sufficiency studies for vitamin D, which collectively show higher levels reduce risk with p<0.0000000001 (1 in 115,066,047,903,039,356,928 vigintillion).
Standard of Care (SOC) for COVID-19 in the study country,
the USA, is very poor with very low average efficacy for approved treatments1.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
|
risk of case, 74.1% lower, RR 0.26, p = 0.01, high D levels 22 of 106 (20.8%), low D levels 22 of 25 (88.0%), NNT 1.5, inverted to make RR<1 favor high D levels, odds ratio converted to relative risk.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Wagner et al., 31 May 2025, prospective, USA, peer-reviewed, mean age 64.3, 12 authors, study period July 2020 - December 2021, trial NCT04482673 (history).
Contact: wagnercl@musc.edu.
Exploring the association between vitamin D status and Corona Virus-19 infection in a cohort of adults aged 50 years and older
Clinical Nutrition Open Science, doi:10.1016/j.nutos.2025.05.007
Objective: Evaluate the association between vitamin D (vitD) status and Corona Virus-19 (COVID-19) infection in adults aged 50 years and older. Design: Adults ≥50 undergoing COVID-19 testing from July 2020 to December 2021, without prior vaccination, consented to blood analysis. SARS-CoV-2 PCR confirmed current COVID-19 infection. VitD status was assessed via 25(OH)D concentration (LCMS/MS, ZRT Labs, Portland, OR). Sociodemographic data were collected at enrollment. Statistical analyses (SAS 9.4) examined associations between sociodemographics, COVID-19, and vitD status. Multivariate logistic regression analyzed factors linked to COVID-19 or vitD status. Results: Of 131 participants, 46.6% were 65 years old, 71.0% married, 19.9% Black American, 36.6% male, 38.9% Medicaid/Medicare/self-pay, and 42.8% BMI30. VitD status and Black American (p=0.0001) significantly associated with COVID-19 infection (p=0.0001). Black American (p=0.0003), males (p=0.003), and BMI (p=0.007) were inversely associated with 25(OH)D concentration. In a multiple logistic regression model predicting COVID-19 infection, only vitamin D status remained significant after controlling for certain sociodemographic and clinical factors (p<0.0001, OR 0.92, 95% CI 0.89-0.95). Of the 44 COVID-positive participants, 35 (79.6%) were hospitalized and 19 (43.2%) were admitted to the Intensive Care Unit (ICU). Hospitalization due to COVID-19 was associated with age 65 years old (p=0.02; OR 12.0, 95% CI 1.34-106.79), male (p=0.02, OR 10.7, 95% CI 1.20-94.73), and 25(OH)D <40 ng/mL (p=0.0006, OR 42.5, 95% CI 3.90-461.01). In multivariate analysis, J o u r n a l P r e -p r o o f the association between vitamin D status and the risk of COVID-related hospitalization remained significant and inversely associated (p=0.03, OR 0.88, 95% CI 0.78-0.99). In unadjusted analysis, COVID pneumonia was associated with male sex (p=0.049; OR 4.6, 95% CI 1.06-20.16 ) and 25(OH)D <40 ng/mL (p=0.006, OR 18.8, 95% CI 1.9-184.10). Participants with COVID infection and 25(OH)D <20 ng/mL were 2.1 times more likely to be admitted to ICU/death (p=0.03). In unadjusted analysis, ICU admission and/or death were linked to age 65 years (p=0.0002, OR 16.9, 95% CI 3.63-78.56), Medicaid/Medicare/self-pay insurance status (p=0.004, OR 0.1, 0.04-0.56), and 25(OH)D <20 (p=0.03, OR 3.9, 1.09-13.66) and <40 ng/mL (p=0.03); however, only age ≥65 remained significant in multivariate analysis (p=0.04, OR 6.7, CI 1.05-43.0). Conclusions: Lower 25(OH)D concentration was a significant predictor and/or contributor to COVID-19 infection, suggesting the importance of maintaining adequate vitamin D status in reducing infection risk and mitigating severe outcomes.
Presentations
References
Bergman, Lindh, Bjorkhem-Bergman, Lindh, Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, PloS one, doi:10.1371/journal.pone.0065835
Bergman, Norlin, Hansen, Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study, BMJ open, doi:10.1136/bmjopen-2012-001663
Bryson, Nash, Norval, Does vitamin D protect against respiratory viral infections?, Epidemiol Infect, doi:10.1017/S0950268814000193
Charoenngam, Holick, Immunologic Effects of Vitamin D on Human Health and Disease, Nutrients, doi:10.3390/nu12072097
Foong, Bosco, Jones, The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function, Am J Respir Cell Mol Biol, doi:10.1165/rcmb.2014-0356OC
Garg, Kim, Whitaker, Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 -COVID-NET, 14 States, March 1-30, 2020, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm6915e3
Garland, Comstock, Garland, Helsing, Shaw et al., Serum 25(OH)D and colon cancer: Eight-year prospective study, Lancet
Garland, Garland, Gorham, Young, Geographic variation in breast cancer mortality in the United States: A hypothesis involving exposure to solar radiation, Prev Med
Giovannucci, Liu, Hollis, Rimm, 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study, Archives of internal medicine, doi:10.1001/archinte.168.11.1174
Grant, The roles of vitamin D, temperature, and viral infections in seasonal risk of acquiring asthma, Am J Respir Crit Care Med, doi:10.1164/ajrccm.179.11.1072a
Grant, Vitamin, Status May Help Explain Racial Disparities in Pancreatic Cancer Incidence and Mortality in the United States. Clinical gastroenterology and hepatology : J o u r n a l P r e -p r o o f the official clinical practice journal of the American Gastroenterological Association, doi:10.1016/j.cgh.2019.12.033
Green, Cod liver oil and tuberculosis, BMJ, doi:10.1136/bmj.d7505
Hamilton, Mcneil, Hollis, Profound Vitamin D Deficiency in a Diverse Group of Women during Pregnancy Living in a Sun-Rich Environment at Latitude 32 degrees N, International journal of endocrinology, doi:10.1155/2010/917428
Hamming, Timens, Bulthuis, Lely, Navis et al., Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis, J Pathol, doi:10.1002/path.1570
Hansdottir, Monick, Vitamin D effects on lung immunity and respiratory diseases, Vitam Horm, doi:10.1016/B978-0-12-386960-9.00009-5
Hawrylowicz, Santos, Vitamin D: can the sun stop the atopic epidemic?, Curr Opin Allergy Clin Immunol, doi:10.1097/ACI.0000000000000613
Holick, Binkley, Bischoff-Ferrari, Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline, The Journal of clinical endocrinology and metabolism, doi:10.1210/jc.2011-0385
Hollis, Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D, The Journal of nutrition
Hollis, Johnson, Hulsey, Ebeling, Wagner, Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness, Journal of Bone and Mineral Research, doi:10.1002/jbmr.463
Hollis, Marshall, Savage, Garrett-Mayer, Kindy et al., Vitamin D(3) supplementation, low-risk prostate cancer, and health disparities, The Journal of steroid biochemistry and molecular biology, doi:10.1016/j.jsbmb.2012.11.012
Hollis, Wagner, Drezner, Binkley, Circulating vitamin D3 and 25hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status, The Journal of steroid biochemistry and molecular biology, doi:10.1016/j.jsbmb.2006.12.066
Hollis, Wagner, Substantial Vitamin D Supplementation Is Required during the Prenatal Period to Improve Birth Outcomes, Nutrients, doi:10.3390/nu14040899
J O U R N A L P R E, None
Johnson, Wagner, Hulsey, Mcneil, Ebeling et al., Vitamin D Deficiency and Insufficiency is Common during Pregnancy, American journal of perinatology, doi:10.1016/j.ajog.2011.03.022
Keum, Lee, Greenwood, Manson, Giovannucci, Vitamin D supplementation and total cancer incidence and mortality: a meta-analysis of randomized controlled trials, Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, doi:10.1093/annonc/mdz059
Li, Hannah, Durbin, Multivariate Analysis of Factors Affecting COVID-19 Case and Death Rate in U.S. Counties: The Significant Effects of Black Race and Temperature, MedRxiv, doi:10.1101/2020.04.17.20069708
Maclaughlin, Holick, Aging decreases the capacity of the skin to produce vitamin D 3, The Journal of clinical investigation
Martineau, Jolliffe, Hooper, Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ, doi:10.1136/bmj.i6583
Mcfee, COVID-19 Laboratory Testing/CDC Guidelines, Dis Mon, doi:10.1016/j.disamonth.2020.101067
Mcnally, Leis, Matheson, Karuananyake, Sankaran et al., Vitamin D deficiency in young children with severe acute lower respiratory infection, Pediatr Pulmonol
Meng, Li, Liu, The role of vitamin D in the prevention and treatment of SARS-CoV-2 infection: A meta-analysis of randomized controlled trials, Clin Nutr, doi:10.1016/j.clnu.2023.09.008
Mirzakhani, Litonjua, Mcelrath, Early pregnancy vitamin D status and risk of preeclampsia, The Journal of clinical investigation, doi:10.1172/JCI89031
Olliver, Spelmink, Hiew, Meyer-Hoffert, Henriques-Normark et al., Immunomodulatory Effects of Vitamin D on Innate and Adaptive Immune Responses to Streptococcus pneumoniae, The Journal of infectious diseases, doi:10.1093/infdis/jit355
Urashima, Segawa, Okazaki, Kurihara, Wada et al., Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren, The American journal of clinical nutrition, doi:10.3945/ajcn.2009.29094
Vignera, Cannarella, Condorelli, Torre, Aversa et al., Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D, International Journal of Molecular Sciences, doi:10.3390/ijms21082948
Wang, Wang, Jiang, Prevalence of vitamin D deficiency and associated risk of all-cause and cause-specific mortality among middle-aged and older adults in the United States, Front Nutr, doi:10.3389/fnut.2023.1163737
Young, Underdahl, Carpenter, Vitamin D intake and susceptibility of mice to experimental swine influenza virus infection, Proc Soc Exp Biol Med
Zhang, Cheng, He, Li, Ma et al., Effect of various doses of vitamin D supplementation on pregnant women with gestational diabetes mellitus: A randomized controlled trial, Exp Ther Med, doi:10.3892/etm.2016.3515
Zhang, Tu, Manson, Racial/Ethnic Differences in 25-Hydroxy Vitamin D and Parathyroid Hormone Levels and Cardiovascular Disease Risk Among Postmenopausal Women, J Am Heart Assoc, doi:10.1161/JAHA.118.011021
Zittermann, Schleithoff, Koerfer, Vitamin D insufficiency in congestive heart failure: why and what to do about it?, Heart failure reviews
Zou, Chen, Zou, Han, Hao et al., Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection, Front Med, doi:10.1007/s11684-020-0754-0
DOI record:
{
"DOI": "10.1016/j.nutos.2025.05.007",
"ISSN": [
"2667-2685"
],
"URL": "http://dx.doi.org/10.1016/j.nutos.2025.05.007",
"alternative-id": [
"S2667268525000567"
],
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Exploring the association between vitamin D status and Corona Virus-19 infection in a cohort of adults aged 50 years and older"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "Clinical Nutrition Open Science"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.nutos.2025.05.007"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2025 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism."
}
],
"author": [
{
"ORCID": "https://orcid.org/0000-0003-2764-6533",
"affiliation": [],
"authenticated-orcid": false,
"family": "Wagner",
"given": "Carol L.",
"sequence": "first"
},
{
"affiliation": [],
"family": "Baatz",
"given": "John E.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ebeling",
"given": "Myla",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Newton",
"given": "Danforth A.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Shary",
"given": "Judith R.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Gregoski",
"given": "Mathew",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Wagner",
"given": "Mark T.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Zava",
"given": "David",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Baggerly",
"given": "Carole",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ketchens",
"given": "Sonya",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Korte",
"given": "Jeffrey",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Hollis",
"given": "Bruce W.",
"sequence": "additional"
}
],
"container-title": "Clinical Nutrition Open Science",
"container-title-short": "Clinical Nutrition Open Science",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"clinicalnutritionopenscience.com",
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2025,
5,
27
]
],
"date-time": "2025-05-27T22:46:47Z",
"timestamp": 1748386007000
},
"deposited": {
"date-parts": [
[
2025,
5,
27
]
],
"date-time": "2025-05-27T22:46:47Z",
"timestamp": 1748386007000
},
"indexed": {
"date-parts": [
[
2025,
5,
28
]
],
"date-time": "2025-05-28T04:21:42Z",
"timestamp": 1748406102150,
"version": "3.41.0"
},
"is-referenced-by-count": 0,
"issued": {
"date-parts": [
[
2025,
5
]
]
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
5,
1
]
],
"date-time": "2025-05-01T00:00:00Z",
"timestamp": 1746057600000
}
},
{
"URL": "https://www.elsevier.com/legal/tdmrep-license",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
5,
1
]
],
"date-time": "2025-05-01T00:00:00Z",
"timestamp": 1746057600000
}
},
{
"URL": "http://creativecommons.org/licenses/by-nc-nd/4.0/",
"content-version": "vor",
"delay-in-days": 22,
"start": {
"date-parts": [
[
2025,
5,
23
]
],
"date-time": "2025-05-23T00:00:00Z",
"timestamp": 1747958400000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S2667268525000567?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S2667268525000567?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"prefix": "10.1016",
"published": {
"date-parts": [
[
2025,
5
]
]
},
"published-print": {
"date-parts": [
[
2025,
5
]
]
},
"publisher": "Elsevier BV",
"reference-count": 0,
"references-count": 0,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S2667268525000567"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"title": "Exploring the association between vitamin D status and Corona Virus-19 infection in a cohort of adults aged 50 years and older",
"type": "journal-article",
"update-policy": "https://doi.org/10.1016/elsevier_cm_policy"
}