Vitamin D and COVID-19

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a primary concern among the nations worldwide as the virus is highly contagious. Hence, there is a pressing need to develop effective preventive and therapeutic strategies to combat this global public health problem.

COVID-19 infection is associated with the increased production of pro-inflammatory cytokines, increased risk of pneumonia, sepsis and acute respiratory distress syndrome. Accumulating evidence suggests that Vitamin D has antiviral, immunomodulatory and anti-inflammatory actions.

It is seen that the fatality rate of COVID-19 increases with latitude (5.2% in northern latitudes and 0.7% in southern latitudes). This can be attributed to less sunlight exposure in countries in northern latitudes predisposing them to higher prevalence of Vitamin D deficiency. Furthermore, since Vitamin D deficiency increases with age, older population is likely to suffer from severe ARDs due to SARS-CoV-2. It has been reported that while the case fatality rate (CFR) of COVID-19 is 1.4%, it is much higher in patients with pre-existing co-morbidities such as cardiovascular disease (13.2%), diabetes (9.2%), hypertension (8.4%) and respiratory disease (8.0). This can also be ascribed to the low Vitamin D levels commonly associated with these disorders.

A meta-analysis of 25 randomized clinical trials has also suggested that regular oral Vitamin D2/D3 intake (in doses up to 2000 IU/d) is protective against acute respiratory tract infection, especially in Vitamin D deficient individuals. Therefore, it seems logical to provide prophylactic supplementation and adjuvant therapy of Vitamin D in order to boost the immune system and to prevent and reduce the severity of COVID-19 infection especially in older population with co-morbidities.

Reference: Khemka A, Suri A, Singh NK, et al. Role of Vitamin D Supplementation in Prevention and Treatment of COVID-19. Indian J Clin Biochem. 2020;35(4):1-2.

Further reading

The role of Vitamin D in the prevention of COVID-19 infection and mortality

WHO declared SARS-CoV–2 a global pandemic. Little is known about the potential protective factors. Previous studies identified associations between higher levels of ACE2 and better coronavirus disease health outcomes. In the lung, ACE2 protects against acute lung injury. Calcitriol (1,25- dihydroxyVitamin D3) exerts pronouncedly impacts on ACE2/Ang(1–7)/MasR axis with enhanced expression of ACE2. Ilie, et al., hypothesized that Vitamin D may play a protective role for SARS-CoV2 infections. Thus, they conducted a study to assess if there is any association between the mean levels of Vitamin D in various countries and the mortality caused by COVID–19. They also identified if there is any association between the mean Vitamin D levels in various countries and the number of cases of COVID–19. The authors identified the mean levels of Vitamin D for 20 Europeans Countries for which they have also got the data regarding the morbidity and mortality caused by COVID-19. The mean level of Vitamin D (average 56 mmol/L, STDEV 10.61) in each country was strongly associated with the number of cases/1 M (mean 295.95, STDEV 298.73 p=0.004, respectively with the mortality/1M (mean 5.96, STDEV 15.13, p < 0.00001). Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of population for COVID-19. The investigators believe that we can advise Vitamin D supplementation to protect against SARS-CoV2 infection.
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Vitamin D and SARS-CoV-2 virus/COVID-19 disease

Vitamin D is essential for good health. (2) Many people, particularly those living in northern latitudes (such as the UK, Ireland, Northern Europe, Canada and the northern parts of the USA, northern India and China), have poor Vitamin D status, especially in winter or if confined indoors. Vitamin D status may be exacerbated during this COVID-19 crisis (eg, due to indoor living and hence reduced sun exposure), and anyone who is self-isolating with limited access to sunlight is advised to take a Vitamin D supplement according to their Government’s recommendations for the general population (ie, 400 IU/day for the UK7 and 600 IU/ day for the USA [800 IU for >70 years] and the European Union (EU).

Current evidence-based advice for the prevention of Vitamin D deficiency includes:

  • Supplementation with Vitamin D according to Government guidelines
  • Consumption of a nutritionally balanced diet
  • Safe sunlight exposure to boost Vitamin D status
  • Appropriate diet and lifestyle measures
  • Follow specific guidelines on the management of Vitamin D deficiency in adults with, or at risk of developing, bone disease

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Evidence that Vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths

Several observational studies and clinical trials reported that Vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of Vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyVitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that Vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of Vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher Vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship?

An inadequate supply of Vitamin D has a variety of skeletal and non-skeletal effects. There is ample evidence that various non-communicable diseases (hypertension, diabetes, CVD, metabolic syndrome) are associated with low Vitamin D plasma levels. These comorbidities, together with the often-concomitant Vitamin D deficiency, increase the risk of severe COVID-19 events. Much more attention should be paid to the importance of Vitamin D status for the development and course of the disease. Particularly in the methods used to control the pandemic (lockdown), the skin's natural Vitamin D synthesis is reduced when people have few opportunities to be exposed to the sun. The short half-lives of the Vitamin therefore make an increasing Vitamin D deficiency more likely. Specific dietary advice, moderate supplementation or fortified foods can help prevent this deficiency. In the event of hospitalization, the status should be urgently reviewed and, if possible, improved
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Vitamin D for COVID-19: A case to answer?

  • From a mechanistic angle, there are good reasons to postulate that Vitamin D favourably modulates host responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), both in the early viraemic and later hyperinflammatory phases of COVID-19.
  • Vitamin D metabolites have long been known to support innate antiviral effector mechanisms, including induction of antimicrobial peptides and autophagy.
  • Two ecological studies have reported inverse correlations between national estimates of Vitamin D status and COVID-19 incidence and mortality in European countries.
  • Low circulating 25(OH)D concentrations have also been reported to associate with susceptibility to SARS-CoV-2 infection.
  • Results of clinical trials on benefit of Vitamin D supplementation in COVID-19 patients are still pending. It would seem uncontroversial to enthusiastically promote efforts to achieve reference nutrient intakes of Vitamin D, which range from 400 IU/day in the UK to 600–800 IU/day in the USA.
  • These are predicated on benefits of Vitamin D for bone and muscle health, but there is a chance that their implementation might also reduce the impact of COVID-19 in populations where Vitamin D deficiency is prevalent; there is nothing to lose from their implementation, and potentially much to gain.

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Vitamin D status and outcomes for hospitalized older patients with COVID-19

A retrospective study was conducted to determine whether these patients have worse outcomes with COVID-19. The cohort consisted of patients aged ≥ 65 years presenting with symptoms consistent with COVID-19 (n=105). All patients were tested for serum 25-hydroxyvitamin D (25(OH)D) levels during acute illness. Diagnosis of COVID-19 was confirmed via viral reverse transcriptase PCR swab or supporting radiological evidence. COVID-19-positive arm (n=70) was sub-divided into Vitamin D-deficient (≤30 nmol/L) (n=39) and -replete groups (n=35). Subgroups were assessed for disease severity using biochemical, radiological and clinical markers. Primary outcome was in-hospital mortality. Secondary outcomes were laboratory features of cytokine storm, thoracic imaging changes and requirement of non-invasive ventilation (NIV). COVID-19-positive arm demonstrated lower median serum 25(OH)D level of 27 nmol/L (IQR=20–47 nmol/L) compared with COVID-19-negative arm, with median level of 52 nmol/L (IQR=31.5–71.5 nmol/L) (p=0.0008). Among patients with Vitamin D deficiency, there was higher peak D-dimer level (1914.00 μgFEU/L vs. 1268.00 μgFEU/L) (p=0.034) and higher incidence of NIV support and high dependency unit admission (30.77% vs. 9.68%) (p=0.042). No increased mortality was observed between groups. Older adults with Vitamin D deficiency and COVID-19 may demonstrate worse morbidity outcomes. Vitamin D status may be a useful prognosticator.
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