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  Table of Contents    
Year : 2021  |  Volume : 38  |  Issue : 7  |  Page : 4-5  

The link between vitamin D deficiency and COVID-19

Department of Pulmonary Medicine, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission04-Dec-2020
Date of Acceptance08-Dec-2020
Date of Web Publication06-Mar-2021

Correspondence Address:
Devasahayam Jesudas Christopher
Department of Pulmonary Medicine, Christian Medical College, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/lungindia.lungindia_921_20

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How to cite this article:
Christopher DJ, Isaac BT, Thangakunam B. The link between vitamin D deficiency and COVID-19. Lung India 2021;38, Suppl S1:4-5

How to cite this URL:
Christopher DJ, Isaac BT, Thangakunam B. The link between vitamin D deficiency and COVID-19. Lung India [serial online] 2021 [cited 2021 Apr 16];38, Suppl S1:4-5. Available from: https://www.lungindia.com/text.asp?2021/38/7/4/310915

One of the factors that has been invoked with regard to the risk and severity of COVID-19 is vitamin D deficiency. There is available evidence to support this hypothesis. vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH) D] <50 nmol/L) is present in 30%–60% of the populations of western, southern, and eastern Europe and in up to 80% of populations in Middle-Eastern countries.[1] In India also, it is very high and the prevalence of vitamin D deficiency (25[OH] D <20 nmol/L) has ranged from 40% to 99%, with most of the studies reporting a prevalence of 80%–90%.[2] vitamin D deficiency is common globally, and serum 25(OH) D levels follow a well-known seasonal and geographical pattern.[3] Spain, located in temperate zones of the Northern Hemisphere, but with a higher prevalence of vitamin D deficiency, has reached very high rates of SARS-CoV-2 infection and lethality.[3],[4]

Vitamin D is a steroid hormone involved in the modulation of the innate and acquired immune system and also in the production of antimicrobial peptides, such as cathelicidin and humanβ-defensin-2, as well as in the expression of genes involved in the intracellular destruction of pathogens.[5],[6],[7] Thrombotic complications are common in COVID-19 patients. Interestingly, vitamin D is also involved in the regulation of thrombotic pathways, and vitamin D deficiency is associated with an increase in thrombotic episodes.[8]

The known risk factors for low vitamin D status are old age and the underlying medical disorders such as hypertension, diabetes mellitus, cardiovascular disorders, and cancer. These are also poor prognostic factors for COVID-19.[9],[10],[11],[12],[13] Finally, the downregulation of ACE2 by SARS-CoV-2 leads to a dysregulation of the renin–angiotensin system, which contributes to the “cytokine storm” that precedes acute respiratory distress syndrome characteristic of the severe form of COVID-19. In this sense, vitamin D can inhibit pro-inflammatory cytokine production in human monocytes/macrophages.[14]

Therefore, there is a strong case for invoking a link between vitamin D deficiency and both susceptibility to COVID-19 infection and disease severity and death.

Hermandez et al. showed that vitamin D deficiency (serum 25[OH]D levels <20 ng/mL) was found in 82.2% of COVID-19 cases and 47.2% of population-based controls (P < 0.0001). Levels of 25(OH) D inversely correlated with serum ferritin (P = 0.013) and D-dimer levels (P = 0.027). vitamin D-deficient COVID-19 patients had a greater prevalence of hypertension and cardiovascular diseases, raised serum ferritin and troponin levels, as well as a longer length of hospital stay.[15]

Kaufman et al. matched the results of SARS-CoV-2 testing performed in a laboratory from mid-March through mid-June 2020, with 25(OH)D results from the preceding 12 months. They showed an association between lower SARS-CoV-2 positivity rates and higher circulating 25(OHD levels, which remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio [OR], 0.984 per ng/mL increment; P < 0.001).[16] Davies et al. analyzed the global daily reports of fatalities and recoveries from 239 locations from January 22, 2020, to April 9, 2020, using a novel causal inference analysis and showed that vitamin D status plays a key role in COVID-19 outcomes.[17]

It appears prudent to supplement vitamin D screen and treat patients with vitamin D deficiency with the hope of reducing their risk of contracting COVID-19 and also reducing the severity. The key question is the effect of short-term vitamin D supplementation in improving outcomes. Rastogi et al. randomized asymptomatic or mildly symptomatic SARS-CoV-2 RNA-positive vitamin D-deficient (25[OH]D <20 ng/mL) Indian individuals to receive high dose (60,000 IU) of cholecalciferol for 7 days or placebo. Greater proportion of those who received cholecalciferol turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen.[18] A more dramatic short-term response to treatment was shown by Entrenas Castillo et al. who randomized 76 consecutive patients hospitalized with COVID-19 infection to calcifediol or no calcifediol. Of 50 patients treated with calcifediol, one required admission to the intensive care unit (ICU) (2%), whereas of 26 untreated patients, 13 required admission (50%) (P < 0.001). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.[19]

The link between vitamin D and COVID-19 remains an important factor for further research with large well-controlled studies, particularly focusing on acute response to treatment early in the course of disease.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, et al. Current vitamin D status in European and middle east countries and strategies to prevent vitamin D deficiency: A position statement of the European calcified tissue society. Eur J Endocrinol 2019;180:23-54.  Back to cited text no. 1
Aparna P, Muthathal S, Nongkynrih B, Gupta SK. Vitamin D deficiency in India. J Fam Med Prim Care 2018;7:324.  Back to cited text no. 2
González-Molero I, Morcillo S, Valdés S, Pérez-Valero V, Botas P, Delgado E, et al. Vitamin D deficiency in Spain: A population-based cohort study. Eur J Clin Nutr 2011;65:321-8.  Back to cited text no. 3
Khafaie MA, Rahim F. Cross-country comparison of case fatality rates of COVID-19/SARS-COV-2. Osong Public Health Res Perspect 2020;11:74-80.  Back to cited text no. 4
Alvarez-Rodriguez L, Lopez-Hoyos M, Garcia-Unzueta M, Amado JA, Cacho PM, Martinez-Taboada VM. Age and low levels of circulating vitamin D are associated with impaired innate immune function. J Leukoc Biol 2012;91:829-38.  Back to cited text no. 5
Gois PH, Ferreira D, Olenski S, Seguro AC. Vitamin D and infectious diseases: Simple bystander or contributing factor? Nutrients 2017;9:651.  Back to cited text no. 6
Watkins RR, Lemonovich TL, Salata RA. An update on the association of vitamin D deficiency with common infectious diseases. Can J Physiol Pharmacol 2015;93:363-8.  Back to cited text no. 7
Mohammad S, Mishra A, Ashraf MZ. Emerging role of Vitamin D and its associated molecules in pathways related to pathogenesis of thrombosis. Biomolecules 2019;9:649.  Back to cited text no. 8
Ananthakrishnan AN, Cheng SC, Cai T, Cagan A, Gainer VS, Szolovits P, et al. Association between reduced plasma 25-hydroxy vitamin D and increased risk of cancer in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014;12:821-7.  Back to cited text no. 9
Schwalfenberg G. Vitamin D and diabetes. Can Fam Physician 2008;54:864-6.  Back to cited text no. 10
Joukar F, Naghipour M, Hassanipour S, Salari A, Alizadeh A, Saeidi-Saedi H, et al. Association of serum levels of vitamin D with blood pressure status in northern Iranian population: The PERSIAN Guilan Cohort Study (PGCS). Int J Gen Med 2020;13:99-104.  Back to cited text no. 11
Mosekilde L. Vitamin D and the elderly. Clin Endocrinol (Oxf) 2005;62:265-81.  Back to cited text no. 12
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.  Back to cited text no. 13
Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, et al. Vitamin D inhibits monocyte/macrophage pro-inflammatory cytokine production by targeting mitogen-activated protein kinase phosphatase 1. J Immunol 2012;188:2127-35.  Back to cited text no. 14
Hernández JL, Nan D, Fernandez-Ayala M, García-Unzueta M, Hernández-Hernández MA, López-Hoyos M, et al. Vitamin D Status in Hospitalized Patients with SARS-CoV-2 Infection. J Clin Endocrinol Metab. 2020 Oct 27:dgaa733. doi: 10.1210/clinem/dgaa733. Epub ahead of print. PMID: 33159440; PMCID: PMC7797757.  Back to cited text no. 15
Kaufman HW, Niles JK, Kroll MH, Bi C, Holick MF. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS One 2020;15:e0239252.  Back to cited text no. 16
Davies G, Garami AR, Byers JC. Evidence supports a causal role for vitamin D status in COVID-19 outcomes. medRxiv 2020.05.01.20087965; doi: https://doi.org/10.1101/2020.05.01.20087965. [Last accessed on 2020 Nov 21].  Back to cited text no. 17
Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)Postgraduate Medical Journal Published Online First: 12 November 2020. doi: 10.1136/postgradmedj-2020-139065.  Back to cited text no. 18
Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcalá Díaz JF, López Miranda J, Bouillon R, et al. Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study. J Steroid Biochem Mol Biol 2020;203:105751.  Back to cited text no. 19


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