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 Table of Contents  
Year : 2020  |  Volume : 11  |  Issue : 2  |  Page : 71-80

Vitamin D and its role in coronavirus disease 2019 (COVID-19)

1 Eris Lifesciences Limited, Mumbai, Maharashtra, India
2 Dr. Mohan’s Diabetes Specialities Centre & Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India

Date of Submission09-Apr-2020
Date of Decision21-Apr-2020
Date of Acceptance22-Apr-2020
Date of Web Publication24-Jun-2020

Correspondence Address:
Dr. Viraj Ramesh Suvarna
C-35, Rose Blossom, Sitladevi Temple Road, Mahim, Mumbai 400016, Maharashtra.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JOD.JOD_18_20

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The unprecedented (in scale, scope) coronavirus disease 2019 (COVID-19) pandemic has taken the world by storm. Cases and case fatality rates are mounting and in this panic-stricken environment, where there are no specific antinovel corona viral drugs or vaccines, doctors are experimenting with drugs that have not been specifically approved for this virus. Against this backdrop, a review article has been written based on locating, selecting, extracting, and synthesizing relevant available in vitro and clinical data on the use of vitamin D as an innate immunity boosting agent, and its possible effects in certain viral (including corona viral) and other acute respiratory tract infections. Vitamin D is not only a micronutrient or vitamin, but also a hormone that has vitamin D receptors on cells all over the body. Vitamin D deficiency/insufficiency is a pandemic, though not infectious, and correcting vitamin D deficiency or insufficiency is required. Whether vitamin D has specific effects against this novel coronavirus in patients with COVID-19 is not known, as there is no randomized controlled clinical trial on its use in such patients. Perhaps there is need for research in this area and particularly when people cannot get adequately exposed to the sun due to the lockdown, taking vitamin D supplements may help them become vitamin D sufficient. Whether it will be sufficient in their fight against COVID-19 is a question that needs to be answered through appropriate research.

Keywords: ACE-2, corona, COVID-19, diabetes, immunomodulatory, innate immunity, prediabetes, respiratory tract infections, SARS-CoV-2, spike protein, vitamin D

How to cite this article:
Suvarna VR, Mohan V. Vitamin D and its role in coronavirus disease 2019 (COVID-19). J Diabetol 2020;11:71-80

How to cite this URL:
Suvarna VR, Mohan V. Vitamin D and its role in coronavirus disease 2019 (COVID-19). J Diabetol [serial online] 2020 [cited 2021 Feb 27];11:71-80. Available from: https://www.journalofdiabetology.org/text.asp?2020/11/2/71/287605

  Background about Coronavirus Disease 2019 Top


The novel coronavirus (nCoV) 2019, also called SARS-CoV-2 (severe acute respiratory syndrome), was so named by the World Health Organization (WHO) because the first case of this unusual coronavirus was reported on December 31, 2019 from China (the index case is apparently a shrimp seller from the wet market of Huanan in Wuhan, Hubei province). In fact if it was first discovered just 1 day later, it could have been named 2020![1]

The word “novel” was used because it was not like the earlier coronaviruses, viz., severe acute respiratory syndrome or SARS-CoV (2002) and Middle East respiratory syndrome or MERS (2012). In fact, it belongs to the family of Betacorona RNA (positive sense) viruses, of which there are seven, and four of these viruses cause symptoms and signs, similar to those of a common cold. SARS and MERS were also pandemics (global epidemic) with a case fatality rate of 10% and 35%, respectively. The SARS pandemic ended on July 5, 2003, whereas the MERS epidemic apparently is still smoldering in the Middle East.[1]

Later, on February 11, 2020 the disease caused by this virus was called COVID-19 (COrona VIrus Disease 2019) by the WHO. On March 11, the WHO Director General, Tedros Adhanom Ghebreyesus, named this epidemic as a pandemic as the global spread was such that it qualified to be called a pandemic. In comparison to SARS and MERS, this nCoV 2019 has the lowest case fatality rate, yet it is so infective or contagious (R0 or R naught of 2.68) that it has created panic in the minds of people all over the world, especially in the USA, and the big five in Europe, viz., Italy, Spain, France, the UK, and Germany, besides of course in Iran.[1]

Breaking the chain of transmission

The South Korea model of testing, isolation, quarantine, and contact tracing is being touted as the role model as they effectively flattened the epidemic curve and broke the chain of transmission, but even as this article is being written, there is the fear of a second wave emerging in that country. China was the first country to go through severe morbidity and mortality (>80,000 cases and >3200 deaths) but they also put in place aggressive measures to contain the spread of this virus (e.g., lockdown in Wuhan for 70 days), and now they are seeing a decline of cases and deaths. Interestingly, a majority of those infected (80%) get mild disease, 14% get moderate disease, and only 6% get severe COVID-19, which necessitates intensive care unit (ICU) admission.[1]

Mode of spread from animal to humans

This virus of zoonotic origin is believed to have jumped from animals (bats and pangolin as an intermediate host) to humans and then acquired the ability to spread from humans to humans. Patients of COVID-19 have symptoms such as fever (need not be very high grade), cough (dry, almost like that seen in people on angiotensin-converting enzyme [ACE] inhibitors), and shortness of breath. It is similar to but different from influenza (sometimes called an influenza-like illness [ILI]) or a common cold[2] [Figure 1].
Figure 1: Differences between coronavirus disease 2019 (COVID-19), common cold, and influenza symptomatology (Source: CDC, WHO)

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Mode of transmission from humans to humans

It spreads through droplets that being heavy would not travel too far airborne and drop to the ground within a range of 180cm; hence, the recommendation that one should be at least 6 feet or 2 m away from each other. Either the contact inhales the droplets or touches the face (mouth, eyes, nose––remember MEN for short) and thus the virus gains entry into the host. Being a virus (a bunch of genes in search of a living cell within which to multiply), it cannot survive outside a living cell for too long, but this virus does have the ability to be viable in aerosols for 3h, on copper for 4h, on cardboard for 24h, and on stainless steel or plastic for about 2–3 days.[2]

The WHO did mention that in ICUs in patients on ventilators, it is possible that the aerosolized virions in microdroplets can stay alive for longer than 8h and hence healthcare workers are at the highest risk and need to be provided with personal protective equipment of the highest order (e.g., N95 masks, gloves, goggles, a hazmat suit in some cases).[2]

The novel coronavirus 2019: structure

The virus is named corona from the Spanish word for crown, as its spikes give it this appearance. It has four proteins, viz., the S or spike protein, E or envelope glycoprotein, M or membrane glycoprotein, and N or nucleocapsid protein. The Spike protein has two parts, viz., S1 and S2. S1 helps the virus attach itself to the ACE-2, which is its receptor, in the lower respiratory tract epithelial cells, although this enzyme is also present in vascular endothelium, heart, kidneys, endocrine pancreas, liver and testes. There is a transmembrane serine protease which helps in this attachment process by priming ACE-2 for attachment by the spike protein S1. S2 helps in fusion of the virus with the endosome where a lower pH helps in viral assembly, replication, and release[2] [Figure 2]A and B.
Figures 2: (A, B) Coronavirus structure and replication (Sources: https://pubs.acs.org/doi/10.1021/acscentsci.0c00272#; https://www.nature.com/

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Off-label use of drugs in coronavirus disease 2019

The antimalarial drug, chloroquine, and its hydroxyl version (hydroxychloroquine) have shown effects such as attenuation of the S protein and raising endosomal pH which inhibits viral replication. This is why, as currently there are no approved specific anticorona viral drugs (remdesivir from Gilead Sciences is being evaluated and favilavir/favipiravir has been approved by the China regulator as it is an RNA-dependent RNA polymerase), it is being recommended that where indicated, for example, for treatment of serious COVID-19 patients, or for prophylaxis of close contacts (healthcare workers/household contacts) who look after infected patients. One may try the drug (off-label, though the U.S. Food and Drug Administration [US FDA] has been asked to approve the drug in record time) such a drug, in combination with azithromycin (but one needs to monitor for corrected QT interval interval prolongation).[2]

Vitamin D and its role in coronavirus disease 2019

Where does vitamin D fit into the COVID-19 story? Against this backdrop why should we be thinking that vitamin D will have any role in COVID-19? Its benefits on bone health are well known and bone is itself an endocrine organ. Vitamin D is not only a vitamin or micronutrient but also a hormone (“vitamone”) playing a vital role in human physiology.[3],[4] Vitamin D deficiency is pandemic, yet it is the most underdiagnosed and undertreated nutritional deficiency in the world. Vitamin D is photosynthesized in the skin on exposure to ultraviolet B rays. However, more than 1 billion people worldwide are believed to have vitamin D deficiency.[5] Even in tropical countries such as India, vitamin D deficiency prevails in 40%–99% of population, with most of the studies reporting a prevalence of 60%–90%.[6]

Diabetes and coronavirus disease 2019

India has an estimated 77 million persons with diabetes per the December 2019 International Diabetes Federation (IDF) report, and those with diabetes seem to have a worse outcome if they get COVID-19 as diabetes does suppress the immune system (more so if uncontrolled). ACE-2 expression is lowered in patients with diabetes possibly due to glycosylation; this might explain the increased predisposition to severe lung injury and acute respiratory distress syndrome (ARDS) with COVID-19. Interestingly, diabetes and vitamin D deficiency are also pandemics, although not infectious.

Prevalence of vitamin D deficiency in prediabetes and diabetes: Indian data

Jayashri et al.[7] assessed the prevalence of vitamin D deficiency in an urban south Indian population in 1500 individuals with different grades of glucose tolerance (900 normal glucose tolerance [NGT], 300 prediabetes, and 300 with type 2 diabetes mellitus [T2DM]) who were not on vitamin D supplementation, randomly selected from the Chennai Urban Rural Epidemiological Study (CURES) follow-up study. Anthropometric, clinical examination, and biochemical investigations (25-hydroxyvitamin D [25(OH)D], insulin, glycated hemoglobin [HbA1c], and serum lipids) were measured. Vitamin D deficiency was defined as serum 25(OH)D <20.0 ng/mL, insufficiency as 20–29.9 ng/mL, and sufficiency as ≥30 ng/mL.

Of the 1500 individuals studied, 45% were men and the mean age was 46±12 years. Vitamin D levels lowered with increasing degrees of glucose tolerance (NGT: 21 ± 11; prediabetes: 19 ± 10; T2DM: 18 ± 11 ng/mL, P < 0.001). The overall prevalence of vitamin D deficiency was 55% and was significantly higher among individuals with T2DM (63%) followed by prediabetes (58%) and NGT (51%) [P for trend <0.001]. Women had 1.6 times the risk of vitamin D deficiency compared to men (unadjusted OR: 1.6, 95% confidence interval [CI]: 1.3–2 and adjusted OR: 1.6, 95% CI: 1.2–1.9). However, there was no increasing trend observed with increasing age. The prevalence of abdominal obesity (66% vs. 49%), generalized obesity (80% vs. 64%), metabolic syndrome (45% vs. 37%), and insulin resistance (38% vs. 27%) was significantly higher in those with vitamin D deficiency compared to those without, respectively. This study shows that vitamin D deficiency is highly prevalent in this urban South Indian population and was higher among individuals with T2DM and prediabetes compared to those with NGT.[7]

The classical functions of vitamin D are to regulate calcium–phosphorus homeostasis and control bone metabolism. However, vitamin D deficiency has been reported in several chronic conditions such as cancers, cardiovascular disease, chronic respiratory tract infections (RTIs), diabetes mellitus, and hypertension. These observations, together with experimental studies, suggest a critical role for vitamin D in the modulation of immune function.[21]

Data from observational studies and supplementation trials

Observational and supplementation trials have reported that supplementation with vitamin D reduces the risk of dengue, herpesvirus, hepatitis B and C viruses, human immunodeficiency virus, influenza, respiratory syncytial virus infections, and pneumonia.[8] Results of a community field trial indicated that 25(OH)D concentrations >50 ng/mL (125 nmol/L) vs. <20 ng/mL were associated with a 27% reduction in ILI.[8] High-dose cholecalciferol supplementation rapidly increases circulating cathelicidin (LL-37) levels and improves sepsis-related clinical outcomes. The result of a recent meta-analysis states that vitamin D supplementation can prevent acute respiratory infections (ARIs). Many other observational trials have found that vitamin D deficiency contributes directly to the ARDS.[21] Data from an in vitro trial suggest that calcitriol may exert protective effects on lipopolysaccharide (LPS)-induced lung injury, at least partially, by regulating the balance between the expressions of members of the renin angiotensin aldosterone system (RAAS).[8]

Relationship between the severe acute respiratory syndrome coronavirus 2 and angiotensin converting enzyme 2[


The renin angiotensin (Ang) aldosterone system (RAAS), which includes ACE-1 and ACE-2, is a complex network that has a major role in various biological functions, including blood pressure regulation and water balance.[8] ACE cleaves Ang I into Ang II, whereas ACE-2, a homologue of ACE, functions as an endogenous counter-regulator of ACE by hydrolyzing angiotensin II into Ang (1–7), and angiotensin-1 into angiotensin (1–9).[8]

On binding to the Ang II subtype 1 receptor (AT1R), Ang II causes vasoconstriction, inflammation, and apoptosis, and Ang (1–7) opposes the effects of Ang II. Therefore, the balance between ACE and ACE-2 levels affects the endogenous ratio of Ang II:Ang (1–7). In addition, recombinant ACE-2 was previously reported to improve pulmonary blood flow and oxygenation in LPS-induced lung injury in piglets. Therefore, ACE-2 may protect against acute lung injury[8] [Figure 3].
Figure 3: Relationship between spike protein of novel coronavirus (nCoV) 2019 and angiotensin-converting enzyme 2 (ACE-2) (Source: Zhang et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020;46:586-90)

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Interestingly, the SARS-CoV-2 virus, which is responsible for the ongoing pandemic, enters into human cells via the same receptor, ACE-2. During the course of infection, coronavirus through an S-protein (spike) binds to ACE-2 receptor and get internalized into human cells. Moreover, SARS-CoV-2 was shown to downregulate ACE-2 protein expression in a replication-dependent manner. The loss of ACE-2 function can be a prime event in SARS-CoV-2 infection that leads to increased neutrophil infiltration in the lung and results in exaggerated inflammation and injury causing ARDS.[9]

Mounting evidence indicates that vitamin D is a negative endocrine regulator of RAAS, and that normalization of vitamin D levels can lower RAAS activity via transcriptional suppression of renin expression. Vitamin D also helps in maintaining tight junctions, killing enveloped viruses through induction of cathelicidin and defensins, and reducing production of pro-inflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia.[9] Therefore, targeting the unbalanced RAAS with vitamin D supplementation may be an excellent approach in the treatment of SARS-CoV-2 infection.[10] However, there is no randomized controlled clinical (RCT) trial to prove that the effect of vitamin D3 supplementation in patients with SARS-CoV-2 infection as yet and such studies are obviously needed [Figure 4] and [Figure 5].{Figure 4},
Figure 5: Effect of vitamin D on the innate immune system (anti-inflammatory/immunemodulatory actions) (Source: Sassi et al.[3])

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Other individual studies on vitamin D and its effects on viral and bacterial respiratory tract infections

Danceret al.[9] performed an in vitro study on human and murine primary alveolar epithelial cells with the objective of determining if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS determine its severity. Vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage, and hypoxia. In vitro vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. They concluded that vitamin D deficiency is common in people who develop ARDS. Deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed.[11]

Charan et al.[12] performed a systematic review and meta-analysis of vitamin D for prevention of acute RTIs. Events of RTIs were significantly lower in the vitamin D group as compared to control group (odds ratio [OR] = 0.582 [0.417–0.812], P = 0.001) according to random model. On separate analysis of clinical trials dealing with groups of children and adults, beneficial effect of vitamin D was observed in both, according to fixed model (OR = 0.579 [0.416–0.805], P = 0.001 and OR = 0.653 [0.472–0.9040], P = 0.010, respectively). On using random model beneficial effect persisted in children’s group but became nonsignificant in adults group (OR = 0.579 [0.416–0.805], P = 0.001 and OR = 0.544 [0.278–1.063], P = 0.075, respectively). They concluded that vitamin D supplementation decreases the events related to RTIs. There is need of more well-conducted clinical trials to reach to a certain conclusion.[12]

Martineau et al.[13] performed a systematic review and meta-analysis of individual participant data (IPD) on vitamin D supplementation to prevent acute RTIs. Twenty-five eligible RCTs (total 11,321 participants, aged 0–95 years) were identified. IPD were obtained for 10,933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute RTI among all participants (adjusted OR 0.88, 95% CI 0.81–0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted OR 0.81, 0.72–0.91) but not in those receiving one or more bolus doses (adjusted OR 0.97, 0.86–1.10; P for interaction = 0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25(OH)D levels <25 nmol/L (adjusted OR 0.30, 0.17–0.53) than in those with baseline 25(OH)D levels ≥25 nmol/L (adjusted OR 0.75, 0.60–0.95; P for interaction = 0.006). To convert ng/mL to nmol/L, multiply the ng/mL by 2.5, for example, 50 ng/mL is equivalent to 125 nmol/L. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 0.98, 0.80–1.20, P = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. They concluded that vitamin D supplementation was safe and it protected against acute RTI overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.[13]

Bergman et al.[14] investigated in a double-blind RCT trial if supplementation with vitamin D3 could reduce infectious symptoms and antibiotic consumption among patients with antibody deficiency or frequent RTIs. One hundred and forty patients with antibody deficiency (selective immunoglobulin A subclass deficiency, immunoglobulin G subclass deficiency, common variable immune disorder) and patients with increased susceptibility to RTIs (>4 bacterial RTIs/year) but without immunological diagnosis. Vitamin D3 (4000 IU) or placebo was given daily for 1 year. The primary end point was an infectious score based on five parameters: symptoms from respiratory tract, ears and sinuses, malaise, and antibiotic consumption. Secondary endpoints were serum levels of 25(OH)D3, microbiological findings, and levels of antimicrobial peptides (LL-37, HNP1–3) in nasal fluid. The overall infectious score was significantly reduced for patients allocated to the vitamin D group (202 points) compared with the placebo group (249 points; adjusted relative score 0.771, 95% CI 0.604–0.985, P = 0.04). They concluded that supplementation with vitamin D3 may reduce disease burden in patients with frequent RTIs. The limitation of the study was that it was a single study center, small sample size, and a selected group of patients. The sample size calculation was performed using P = 0.02 as the significance level, whereas the primary and secondary end points were analyzed using the conventional P = 0.05 as the significance level.[14]

A new global collaborative study (funded by National Institute for Health Research [NIHR], UK) has confirmed that vitamin D supplementation can help protect against ARIs. The study, a participant data higher-resolution meta-analysis of 25 RCTs, including more than 11,000 participants, from more than 12 countries, including the USA, Canada, and the UK, has been published online in the British Medical Journal (BMJ).[15] The investigators found that daily or weekly supplementation had the greatest benefit for individuals with the most significant vitamin D deficiency (blood levels below 20 ng/dL)––cutting their risk of respiratory infection in half––and that all participants experienced some beneficial effects from regular vitamin D supplementation. Administering occasional high doses of vitamin D did not produce significant benefits.[16]

Studies show that vitamin D interacts directly with cells responsible for fighting infection. Because of this, researchers conclude that being deficient in vitamin D could increase your risk of getting infected by the deadly coronavirus. Researchers also hypothesized that increasing vitamin D dosage may provide protection against COVID-19. Several studies have shown that taking a daily dosage of up to 4000 IU of vitamin D supplements lowers your risk of RTI. One study involving patients with chronic obstructive pulmonary disease or COPD were given high doses of vitamin D supplements for 1 year. After the study, researchers noted that only those who have severe vitamin D deficiency experienced considerable benefits.[17]

Researchers from The Irish Longitudinal Study on Ageing (TILDA) at Trinity College, Dublin have released a report in response to the COVID-19 pandemic. One in eight Irish adults under 50 years of age was found to be deficient in vitamin D all year round. Only 4% of men and 15% of women took vitamin D supplements. 27% of adults over 70 years of age who were at home were estimated to be deficient. 47% of all adults over 85 years of age are deficient in winter. Staying at home may be a necessity but will reduce physical activity; muscle deconditioning occurs rapidly in these circumstances and vitamin D will help to maintain muscle health and strength in the current crisis.[18]

According to the BMJ 2017 systematic review and meta-analysis, of 25 RCTs, in >11,000 patients who were given vitamin D or placebo, number needed to treat was only four, which means it was necessary to treat only four people who are deficient in vitamin D to prevent one case of ARI. Critical care research also documents the important effect of vitamin D on survival in ICU patients with ARDS. It should be noted that the BMJ systematic review and meta-analysis cited above did not address efficacy against coronavirus infections; in addition, nearly half of the participants in the included studies were infants in India and Afghanistan.[19]

Zhao et al.[20] performed a meta-analysis of observational studies on the association between vitamin D deficiency and community-acquired pneumonia (CAP). Eight observational studies involving 20,966 subjects were included. In this meta-analysis, CAP patients with vitamin D deficiency (serum 25(OH)D levels <20 ng/mL) experienced a significantly increased risk of CAP (OR = 1.64, 95% CIs: 1.00, 2.67), and an obvious decrease of −5.63 ng/mL (95% CI: −9.11, −2.14) in serum vitamin D was shown in patients with CAP. Sensitivity analysis showed that exclusion of any single study did not materially alter the overall combined effect. The evidence from this meta-analysis indicates an association between vitamin D deficiency and an increased risk of patients with CAP. However, well-designed trials are required to determine the explicit effect of vitamin D supplementation.

Supplementation with magnesium and calcium

Magnesium supplementation is recommended when taking vitamin D supplements. Magnesium helps activate vitamin D, which in turn helps regulate calcium and phosphate homeostasis, to influence growth and development of bones. All the enzymes that metabolize vitamin D seem to require magnesium, which acts as a cofactor in enzymatic reactions in the liver and kidney. The dose of magnesium should be in the range of 250–500 mg/day, along with twice that dose of calcium.[21]

  Conclusion Top

In summary, Vitamin D deficiency has been shown to be independently associated with increased risk of viral ARI in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has shown protective effects. The current hypothesis that SARS-CoV-2 can unbalance a high running RAAS in the lung via ACE-2 downregulation, which is followed by inflammation, and hypoxia supports the role of vitamin D in such patients. However, more studies are needed to clarify the effects of vitamin D on patients with COVID-19.Till this question is answered there seems to be no harm in advocating use of vitamin D supplements for those who are vitamin D deficient (<20 ng/mL) or vitamin D insufficient (20–30 ng/mL), so that they become vitamin D sufficient (>30 ng/mL) and are better equipped (innate immunity) to fight this pandemic.

  Addendum Top

A retrospective study by Alipio[22] in 212 laboratory confirmed cases of SARS-CoV-2 looked at serum 25(OH) vitamin D levels in patients with mild and severe COVID-19 infections. He found that there was an inverse relationship. In other words, patients with low levels of vitamin D had more severe COVID-19 infections and vice-versa. The results suggested that an increase in serum 25(OH)D level in the body could either improve clinical outcomes or mitigate worst (severe to critical) outcomes, while a decrease in serum 25(OH)D level in the body could worsen clinical outcomes of COVID-2019 patients. He opined that vitamin D supplementation could possibly improve clinical outcomes of patients infected with COVID-19, but also stated that further research should be conducted in the form of prospective randomized controlled trials, and large population studies are needed to evaluate this recommendation going forward.[22]

The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were studied by Ilie et al.[23] Negative correlations between mean levels of vitamin D (56 mmol/L ± 10.61) in each country and the number of COVID-19 cases/1 M (295.95 ± 298.7, and mortality/1 M (5.96 ± 15.13) were observed. Vitamin D levels were severely low in the aging population, especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. The authors advised that dedicated studies should be performed about vitamin D levels in COVID-19 patients with different degrees of disease severity.[23] Mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategies were compared to investigate the potential impact of vitamin D on A-CMR (adaptive average of time-adjusted case mortality ratio).[24] The authors observed an inverse correlation (correlation coefficient ranging from -0.84 to -1) between high C-Reactive Protein (CRP), an inflammatory marker, and 25(OH)D. Their analysis determined a possible link between high CRP and vitamin D deficiency among the elderly (age greater than or equal to 60 y) in low-income and high-income families. Given that CRP is a surrogate marker for cytokine storm and is associated with vitamin D deficiency, based on retrospective data and indirect evidence, they saw a possible role of vitamin D in reducing complications attributed to unregulated inflammation and cytokine storm. Further research is needed to account for other factors through direct measurement of vitamin D levels in COVID-19 patients.[24]

A recent article in the BMJ Nutrition Prevention & Health by Lanham et al,[25] on vitamin D and SARS-CoV-2/COVID-19 disease, mentioned that while there is some evidence of an association between vitamin D levels and COVID-19 infections, one can definitively answer the hypothesis (does vitamin D supplementation help improve outcomes of COVID-19 patients?) only when we have results from prospective randomised controlled clinical trials. Two such clinical trials are listed on the Chinese Clinical Trials Registry website.[25]

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Conflict of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 3], [Figure 2], [Figure 2], [Figure 5]


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