The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to hundreds of millions of infections worldwide, with over 6 million deaths so far. Many researchers have suggested that low vitamin D levels increase the risk of clinical infection and severe and fatal COVID-19.
A new paper summarizes the increasingly persuasive evidence that early vitamin D supplementation can shorten hospital stay, reduce the need for oxygen, and cut mortality rates.
Despite the development of vaccines and antiviral drugs to prevent and treat COVID-19, the virus continues to emerge as new variants, often with immune escape characteristics, as well as increased transmissibility and/or virulence properties that may underlie the appearance of a variant of concern (VOC). This indicates the need to continue the development of preventatives and therapeutics to counter the clinical threat posed by the virus.
Dietary manipulation has been a prime route of immunomodulation during the pandemic, with the supplementation of various vitamins and minerals being suggested to help strengthen the immune system. However, most of these failed to make it into the mainstream for want of robust clinical evidence.
The current paper, which appears online in the journal Nutrients, addresses the considerable evidence now supporting the efficacy of vitamin D in COVID-19, as well as its safety.
Urban dwellers are at a higher risk for COVID-19 disease and death, while vitamin D deficiency is associated with doubling the risk of severe COVID-19. The relationship with vitamin D levels has also been demonstrated in other studies, with higher vitamin D levels being associated with lower mortality, ICU admission risk, and ventilator use.
Is vitamin D supplementation useful?
An analysis of multiple studies showed that supplementing with vitamin D reduced the risk of severe disease by >60% and mortality risk by 65%. Following this up, the authors also observed that a dose-response relationship appeared to be present, where high-dose vitamin D improved the prognosis of such patients.
A small cohort of approximately 400 patients showed a reduction in deaths due to COVID-19 by almost 90%, though this degree of reduced risk was not observable in all studies. Consistently, however, higher doses of the vitamin, with its antiviral, immunomodulatory, and anti-inflammatory properties, have been associated with fewer hospitalization days and lower requirements for oxygen supplementation.
One research team directly compared a dose of 2000 IU per day with 10,000 IU per day in hospitalized COVID-19 patients for two weeks, showing reduced disease severity with the latter. A multicenter randomized controlled trial from France, COVID-19and Vitamin D TRIAL (COVIT-TRIAL), aimed to examine the differential impact of one dose of vitamin D at 400,000 IU vs. 50,000 IU in older adults with early COVID-19 symptoms lasting less than three days at the time of vitamin D administration, who had one or more high-risk factors for progression to severe illness. This showed lower mortality rates despite a higher rate of relatively minor adverse events.
This remains to be validated; however, since another large international trial, COVID-VIT-D trial, patients who got one dose of 100,000 IU vitamin D at the time of hospital admission improved only if their calcifediol levels were higher initially.
What are the implications?
In keeping with the known roles of vitamin D in the immune response to viral infections and its immunomodulatory role, this molecule has been intensively studied for its potential to improve patient outcomes in COVID-19. By reducing the level of inflammation in response to infection with SARS-CoV-2, vitamin D could prevent the infamous cytokine storm and improve lung function by promoting epithelial repair.
Vitamin D also reduces cardiovascular risk by its effect on the renin-angiotensin-system that helps regulate blood pressure and vascular health; it promotes neutrophil function, and helps avert the thrombotic phenomena associated with severe and progressive COVID-19.
People already taking vitamin D might, perhaps, be more resistant to the virus, as suggested in some previous research on acute respiratory infections. Adequate levels of vitamin D could also help compensate for the lack of sunlight, the bone-depleting effects of glucocorticoid therapy, and relative immobility, protecting against osteoporosis.
At least for those with borderline vitamin D deficiency, “in the context of the COVID-19 pandemic, vitamin D supplementation seems to be an effective preventive and therapeutic tool to be considered.” Being inexpensive and safe in most situations, the use of this vitamin at higher-than-normal doses could be recommended in light of multiple studies that show a favorable effect of this vitamin on COVID-19 prognosis.