Low Vitamin D Levels as a Risk Factor for Greater Covid-19 Severity

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Abstract

ID-19 death rate in 20 European countries.</p><p id="3df5">“Vitamin D levels are 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,” they wrote in a <a href="https://www.researchsquare.com/article/rs-21211/v1">pre-print paper</a> (which has been <a href="https://link.springer.com/article/10.1007%2Fs40520-020-01570-8">peer-reviewed and published</a> in <i>Aging Clinical and Experimental Research</i>)<i>. </i>“Vitamin D has already been shown [by a meta-analysis] to protect against acute respiratory infections and it was shown to be safe. We believe, that we can advise vitamin D supplementation to protect against COVID–19 infection.”</p><h1 id="f048">PART III: META-ANALYSES</h1><p id="2784">Vitamin D has long been known as a key element for immunological health. Two meta-analyses — one integrating <a href="https://pubmed.ncbi.nlm.nih.gov/23840373/">11 clinical trials</a> and the other synthesized <a href="https://www.bmj.com/content/356/bmj.i6583">25 clinical trials</a> — have revealed vitamin D supplementation to be protective against respiratory tract infections. And this protection is more apparent in those with lower levels of vitamin D in their blood.</p><p id="e27b">Both meta-analyses also found that consistent dosing is best — either daily or weekly. One-time large dosing did not help lower the risk of respiratory tract infections. Vitamin D supplementation was also reported as safe.</p><p id="1745">Notably, <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26360">a July meta-analysis</a> published in the <i>Journal of Medical Virology </i>of eight studies (including pre-prints) comprising 1,368 Covid-19 patients found a significant association between vitamin D insufficiency and severe Covid-19. “Patients with poor prognosis (N=634) had significantly lower serum levels of vitamin D compared to those with good prognosis (N=669), representing an adjusted standardized mean difference of ‐5.12,” the study authors at Tulane University in New Orleans, US concluded.</p><h1 id="b326">PART IV: ON-GOING CLINICAL TRIAL</h1><p id="dc7b">The Universit

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y Hospital, Angers is currently conducting a phase III clinical trial (ClinicalTrials.gov Identifier: <a href="https://clinicaltrials.gov/ct2/show/NCT04344041">NCT04344041</a>) that aims to enroll 260 elderly of ≥70 years old diagnosed with COVID-19 within 48 hours. Exclusion criteria entailed anyone who has been taking vitamin D supplements or with medical conditions that cause vitamin D intolerance.</p><p id="fafe">The intervention is high-dose of vitamin D at 400,000 IU or 50,000 IU over 14 days. The main outcome is the death rate from COVID-19. The clinical trial is expected to be completed sometime in July 2020.</p><h1 id="6b82">PART V: REVIEWS</h1><p id="65d5">“For about half the population, taking 5000 IU/day of vitamin D3 or 30,000–35,000 IU/week would raise 25(OH)D concentration to 40 ng/mL,” Dr. William B. Grant, founding director of Sunlight, Nutrition, and Health Research Center in San Francisco, and colleagues wrote in a research review. Dr. Grant also cautioned that the efficacy of vitamin D supplements would depend on factors such as genes, gut health, weight, and baseline vitamin D levels.</p><p id="ccbc">“Several micronutrients may be deficient, and even marginal deficiency may impair immunity. Although contradictory data exist, available evidence indicates that supplementation with multiple micronutrients with immune-supporting roles may modulate immune function and reduce the risk of infection,” agreed Professor Adrian F. Gombart at Oregon State University and colleagues in another <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019735/">2020 research review</a>. “Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc.”</p><p id="037e">“The circumstantial evidence is very strong”, Rose Anne Kenny, a professor of Medical Gerontology at Trinity College Dublin, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239633/">remarked</a> on the vitamin D and COVID-19 link. “We don’t have randomized controlled trial evidence, but how long do you want to wait in the context of such a crisis? We know vitamin D is important for musculoskeletal function, so people should be taking it anyway.”</p></article></body>

PART I: Cohort Studies

This study, “Low plasma 25(OH) vitamin D level is associated with increased risk of COVID‐19 infection: an Israeli population‐based study,” was published in July. Researchers in Israel identified lower overall vitamin D levels in 782 Covid-19 compared to 7,025 non-Covid-19 participants. More importantly, low vitamin D levels increased the odds of hospitalization by 95%, after adjusting for demographics and comorbidities confounders. “Low plasma 25(OH)D level appears to be an independent risk factor for COVID‐19 infection and hospitalization,” the authors concluded.

In a smaller cohort study, titled “Low serum 25‐hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID‐19 are associated with greater disease severity,” researchers measured blood vitamin D levels in 134 people tested positive for Covid-19 in the UK. They found that only 19% of patients admitted to the intensive care unit (ICU) had normal vitamin D levels, and this number is 39.1% in those with non-ICU level severity. This relationship between low baseline vitamin D status and greater Covid-19 severity is also seen in a separate cohort study of 80 patients.

PART II: OBSERVATIONAL STUDY

There’s another observational evidence pointing towards the detriments of lack of vitamin D in the body. Dr. Petre Cristian Ilie, consultant and urological surgeon at Queen Elizabeth Hospital and Norfolk, lead a study examining the relationship between average levels of blood vitamin D and COVID-19 death rate in 20 European countries.

“Vitamin D levels are 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,” they wrote in a pre-print paper (which has been peer-reviewed and published in Aging Clinical and Experimental Research). “Vitamin D has already been shown [by a meta-analysis] to protect against acute respiratory infections and it was shown to be safe. We believe, that we can advise vitamin D supplementation to protect against COVID–19 infection.”

PART III: META-ANALYSES

Vitamin D has long been known as a key element for immunological health. Two meta-analyses — one integrating 11 clinical trials and the other synthesized 25 clinical trials — have revealed vitamin D supplementation to be protective against respiratory tract infections. And this protection is more apparent in those with lower levels of vitamin D in their blood.

Both meta-analyses also found that consistent dosing is best — either daily or weekly. One-time large dosing did not help lower the risk of respiratory tract infections. Vitamin D supplementation was also reported as safe.

Notably, a July meta-analysis published in the Journal of Medical Virology of eight studies (including pre-prints) comprising 1,368 Covid-19 patients found a significant association between vitamin D insufficiency and severe Covid-19. “Patients with poor prognosis (N=634) had significantly lower serum levels of vitamin D compared to those with good prognosis (N=669), representing an adjusted standardized mean difference of ‐5.12,” the study authors at Tulane University in New Orleans, US concluded.

PART IV: ON-GOING CLINICAL TRIAL

The University Hospital, Angers is currently conducting a phase III clinical trial (ClinicalTrials.gov Identifier: NCT04344041) that aims to enroll 260 elderly of ≥70 years old diagnosed with COVID-19 within 48 hours. Exclusion criteria entailed anyone who has been taking vitamin D supplements or with medical conditions that cause vitamin D intolerance.

The intervention is high-dose of vitamin D at 400,000 IU or 50,000 IU over 14 days. The main outcome is the death rate from COVID-19. The clinical trial is expected to be completed sometime in July 2020.

PART V: REVIEWS

“For about half the population, taking 5000 IU/day of vitamin D3 or 30,000–35,000 IU/week would raise 25(OH)D concentration to 40 ng/mL,” Dr. William B. Grant, founding director of Sunlight, Nutrition, and Health Research Center in San Francisco, and colleagues wrote in a research review. Dr. Grant also cautioned that the efficacy of vitamin D supplements would depend on factors such as genes, gut health, weight, and baseline vitamin D levels.

“Several micronutrients may be deficient, and even marginal deficiency may impair immunity. Although contradictory data exist, available evidence indicates that supplementation with multiple micronutrients with immune-supporting roles may modulate immune function and reduce the risk of infection,” agreed Professor Adrian F. Gombart at Oregon State University and colleagues in another 2020 research review. “Micronutrients with the strongest evidence for immune support are vitamins C and D and zinc.”