COVID-19 and Vitamin D Deficiency

Vitamin D deficiency is a global health problem that affects more than one billion children and adults worldwide.[1],[2]

Vitamin D is essential not only for healthy bones, but also for the body’s defense against infections.[3],[4],[5],[6] Numerous studies have shown that insufficient vitamin D intakes are associated with an enhanced risk and severity of respiratory tract infections.[7],[8],[9]

In a large population-based study in Germany, the mortality from respiratory diseases (including influenza and pneumonia) over a 15-year period was found to be three-fold higher in adults with vitamin D deficiency compared to those with a healthy vitamin D level.[10] Based on statistics, 41% of the mortality due to respiratory diseases was attributable to inadequate vitamin D levels.[10]

In 2020, studies investigating the importance of adequate vitamin D levels for a healthy immune response to the new coronavirus, SARS-CoV-2, and the disease associated with it, COVID-19, began to appear. These studies point towards vitamin D deficiency as a factor that contributes to infection with the virus and the severity of disease that occurs when one becomes infected, as discussed below.

The demographics of vitamin D deficiency

The global patterns of COVID-19 mortality reflect those of vitamin D status.

Vitamin D is known as the sunshine vitamin because it is generated within the skin upon exposure to ultraviolet B (UVB) rays, the rays responsible for suntans.[11] Many variables affect UVB exposure (which is different from just being outside in the sun) and therefore influence vitamin D levels in the body.

Latitude strongly influences UVB exposure and vitamin D status.[12],[13] At northern latitudes, very little, if any, vitamin D is produced in the skin during the winter, and vitamin D levels drop unless vitamin D is supplemented.[13],[14] One study showed that young adults living in Pennsylvania, a northern state, had a 3.3-fold higher risk of vitamin D deficiency as compared to those living in Florida, a southern state.[15] States with a substantial portion of their population living at approximately the same latitude as Pennsylvania include Ohio, Missouri, Utah and Nebraska; thus, similar findings would be anticipated in these regions, while the risk is even greater further north.

Scientists have observed that the global patterns of COVID-19 mortality reflect those of vitamin D status. In the winter of 2019-2020, countries in the Northern Hemisphere exhibited higher COVID-19 mortality rates compared to countries in the Southern Hemisphere.[16] In fact, there was an estimated 4.4% increase in COVID-19 mortality for each 1 degree latitude north of 28 degrees North (a parallel that passes through south Texas).

The effect of latitude, and by inference vitamin D status, applies not only to COVID-19 but also to seasonal and pandemic influenza outbreaks.[17],[18] In a retrospective analysis of the 1918-1919 influenza pandemic, there was a substantial correlation between UVB intensity and case fatality rates in 12 different regions of the U.S.[18] Among the states included in the study, the lowest case fatality rates occurred in Texas, which had  the highest UVB irradiance and lowest latitude, while the highest rates were in Connecticut, which had the lowest UVB irradiance and highest latitude.

Age is also a factor,[11] since aging can decrease by more than twofold the capacity of the skin to produce vitamin D.[19] Vitamin D deficiency is extremely common in the elderly for this and other reasons, such as reduced sun exposure, digestive problems, diet inadequacies, comorbidities, and the use of medications.[20] As a result, vitamin D levels tend to be severely low in aging populations.[21],[22],[23] This may be one factor contributing to the fact that some countries with large elderly populations, such as Italy, had such severe COVID-19 outbreaks.[23],[24] Older adults were found to have higher viral loads and, especially those with comorbidities, had higher COVID-19-related fatality rates than younger adults.[24]

Melanin in the skin blocks UVB light, so individuals with darker skin tend to synthesize less vitamin D than those with lighter skin.[25],[26] This may explain, in part, the disparities between infection rates between lighter and darker skin populations. Data from the UK showed that ethnic groups having darker skin were approximately two to four times more likely to die from COVID-19 than were those of white ethnicity.[27],[28] In addition to latitude, age, and skin melanin content, genetic variations play a role in COVID-19 susceptibility among different populations and ethnic groups.[29],[30],[31]

Vitamin D deficiency is common in COVID-19 patients

Low vitamin D levels were found to be an independent risk factor for COVID‐19 infection and hospitalization.

Growing evidence suggests that the majority of COVID-19 patients are deficient or insufficient in vitamin D.[32],[33],[34],[35] In one study, researchers found that 81% of the patients admitted to a hospital ICU had inadequate vitamin D levels.[32] Another study found that low vitamin D levels were an independent risk factor for COVID‐19 infection and hospitalization.[34]

In one of the largest population studies to date, which is currently published as a preprint, scientists assessed the relationship between the prevalence of vitamin D deficiency and a positive coronavirus test result.[36] The study encompassed 4.6 million individuals, spanning across 200 localities in Israel. They found a significant association between low vitamin D levels and the risk of infection, with the highest risk observed for those with severe vitamin D deficiency, defined as 25(OH)D levels lower than 30 nmol/L.

These researchers also found that vitamin D deficiency was more prevalent among ultra-orthodox and Arab communities, reflecting the use of religious clothing that covers most of the skin and blocks UVB light. These population sub-groups had a two- to three-fold increased risk of COVID-19 infection.[36]

The greatest risks of infection were observed among individuals with severe vitamin D deficiency who lived in regions where much of the population was low in vitamin D.[36] The authors suggest that, in areas where vitamin D deficiency is widely prevalent, neighbors are more likely to spread the virus to each other. Conversely, a sort of “herd immunity” may occur in communities with greater average vitamin D levels, not because of any actual antibody-based immunity, but because adequate vitamin D levels reduce the risk of infection and hence the risk of passing the virus along to neighbors.[36]

Adults who are obese are three times more likely to be vitamin D deficient as compared to those with normal body weights.[37],[38] Obesity is associated with cardiovascular metabolic diseases, including diabetes and hypertension, which are conditions that increase the risk and severity of COVID-19 infections.[39],[40],[41] A meta-analysis of 75 studies concluded that obese individuals who had COVID-19 were more than twice as likely to require hospitalization as those with normal body weights.[41]

Multiple studies have found that vitamin D deficiency is associated with the severity of COVID-19 infections as well.[34],[35] Low vitamin D levels contribute to excessive cytokine production and lung inflammation, which increases the risk of hospitalization.[34],[35],[42],[43],[44] In one study of hundreds of individuals with COVID-19, scientists observed that inadequate plasma vitamin D levels raised the odds of hospitalization by 95%, even after adjusting for comorbidities.[34] “Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization,” the authors concluded.

Calcifediol improves outcomes

A groundbreaking study published in August 2020 found a direct effect of vitamin D status on COVID-19 outcomes.[45] In the controlled trial, hospitalized patients were treated with calcifediol, a prescription formulation of 25(OH)D, which is the major circulating form of vitamin D in the body.[11],[22],[46] Calcifediol has been shown to raise blood levels of 25(OH)D more rapidly than vitamin D3.[47]

In a study of COVID-19 patients being admitted to the hospital for their condition, a portion of them received a high dose of oral calcifediol in addition to indicated treatment established by hospital protocols.[40] Outcomes were significantly better in the group receiving calcifediol: only 1 out of 50 patients (2%) required ICU admission, and none of them died, while in the no-calcifediol group, 13 out of 26 patients (50%) required ICU admission, and two died. Consequently, the administration of calcifediol reduced the odds of ICU admission by 93%.

While this study was small, it was the first to show that calcifediol administration could influence outcomes. According to the authors, “Our pilot study demonstrated that administration of a high dose of calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19.”[40]

 

Clearly, there is much we are continuing to learn as we deal with this global pandemic. Research on vitamin D and other nutritional factors that may play a role in COVID-19 is coming out at rapid pace, exceeding that related to any other medical condition affecting humankind. As we look to modern medicine for a solution, it is important to remember that proper nutrition is the foundation for all aspects of good health.

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