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Comprehensive COVID-19 study: Widespread vitamin D deficiency increases the risk of infection, complications, and death

Comprehensive COVID-19 study: Widespread vitamin D deficiency increases the risk of infection, complications, and deathAccording to a new study based on a number of systematic reviews and meta-analyses, the widespread lack of vitamin D increases the risk of being infected with COVID-19. It also increases the risk of complications and death as the result of a derailed immune defense. At the same time, supplementation with vitamin D appears to reduce both disease severity and death among COVID-19 patients, provided blood levels of the nutrient are optimal.

Vitamin D regulates both our innate and adaptive immune defenses by switching on and off different genes and controlling inflammatory processes. These inflammatory processes are a vital part of our defense against infections, but it is crucial that the body can control and stop them once the threat is over. Otherwise, the inflammation risks coming off its hinges, which can result in oxidative stress and damage to healthy cells and tissues.
In their new and very comprehensive umbrella review, the scientists looked at different systematic reviews and meta-analyses to evaluate the large number of studies of vitamin D and COVID-19 infections. The researchers gathered information from different databases such as PubMed, Embase, and Cochrane Library. Out of 74 publications, there were 27 meta-analyses that described the relation between blood levels of vitamin D, vitamin D supplementation, and the severity of COVID-19 infections.
It turned out that low blood levels of vitamin D were associated with significantly increased COVID-19 severity and risk of death. Also, taking vitamin D supplements after COVID-19 had been diagnosed was linked to a significantly lower disease severity, fewer ICU (intensive care unit) admissions, and less death.
Judging from the many reviews and meta-analyses, it seems that too little vitamin D in the blood (below 50 nmol/L) increases the risk of being infected with COVID-19, developing serious complications, and dying of the disease. There is also a link between vitamin D supplementation, fewer complications, and fewer deaths among patients with COVID-19.
According to the researchers, the selected systematic reviews and meta-analyses support another new meta-analysis that showed how vitamin D supplementation lowers all-cause mortality.

  • Infections with COVID-19 (SARS-Cov-2), colds, influenza, HIV, and herpes are caused by different kinds of RNA viruses that continue to mutate
  • It is therefore impossible to produce an effective vaccine.

Vitamin D’s role in relation to COVID-19 and other diseases

In most cases, people who contract COVID-19 don’t notice it or only develop mild symptoms. In more severe cases, the infection causes respiratory problems that can end up as acute respiratory distress syndrome (ARDS). This potentially life-threatening condition is the result of a poorly controlled and derailed immune defense, which can cause hyperinflammation in the airways. Hyperinflammation and other uncontrolled reactions may also occur in blood vessels and other organs. In worst case, they result in organ failure and death. When a COVID-19 infection or influenza becomes life-threatening, it is not the virus in itself that is the problem, it is the fact that the immune defense spins out of control.
This type of unwanted inflammation is also the common thread in ageing and different chronic diseases – including cardiovascular disease, diabetes, cancer, and autoimmune disorders. All of these things make patients more vulnerable to a COVID-19 infection. In their new and very comprehensive study, the scientists look closer at vitamin D’s role in general health, especially with regard to the vitamin’s ability to strengthen and regulate the immune defense:

  • It regulates the immune defense by way of different genetic on-off switches
  • It has antimicrobial activity through stimulation of polypeptides such as cathelicidin and β-defensin in the airways
  • It stimulates interferon that prevents viruses from replicating in infected cells
  • It activates pro-inflammatory cytokines, thereby destroying and removing infected cells from the airways
  • It stimulates and controls macrophages in the innate immune defense’s emergency response
  • It stimulates and regulates T cells in the adaptive immune defense
  • It stimulates B cells and the production of antibodies
  • It strengthens the epithelial cells that are our natural barrier in the respiratory tract, blood vessels, etc.
  • It triggers anti-inflammatory cytokines to prevent the immune reactions from causing unwanted damage to cells and tissues
  • It contributes to broad to immunity, where the macrophages and T cells play a particularly important role in connection with virus infections.

Vitamin D supplementation as prevention and therapy

The scientists conclude that vitamin D supplements may be useful in the prevention of COVID-19, complications, and subsequent death. This is especially relevant for older and vulnerable people, nursing home residents, and people who don’t get enough sunlight. It is should also be noted that people living at norther latitudes are unable to get vitamin D from the sun during the entire winter period where the sun sits too low in the sky. Also, studies show that overweight people have difficulty with utilizing vitamin D from the sun and from supplements and therefore have an increased need for the nutrient.
The researchers also stress the fact that vitamin D has immune-regulating and anti-inflammatory properties that help reduce both disease severity and death risk in people with COVID-19. They call for more studies to help determine the optimal vitamin D dose and duration of supplementation in those infected with the disease.
In countries like Denmark, the health authorities recommend that people take vitamin D throughout the entire winter period. People who don’t get enough sun during the summer period or belong to vulnerable groups are advised to take a vitamin D supplement all year round. Apparently, people have different needs for vitamin D so the important thing is to make sure to have optimal levels of the nutrient in the blood at all times to ensure enough vitamin D for the immune defense and the many other vitamin D-dependent functions.


Fausto Petrelli et al. Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-analysis. Antioxidants 2023

Deirdre K. Tobias, Heike Luttmann-Gibson, Samia Mora, Jacqueline Danik, Vadim Bubes, Trisha Copeland, Meryl S. LeBoff, Nancy R. Cook, I-Min Lee, Julie E. Buring, JoAnn E. Manson. Association of Body Weight With Response to Vitamin D Supplementation and Metabolism. JAMA Network Open, 2023

Iacopo Chiodini et al., Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes. Frontiers in Public Health. 22 December 2021

Asma Kazemi et al. Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis. Advanced Nutrients 2021 Oct

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