Meta-analysis: Lack of vitamin D is related to complicated COVID-19 infections, intensive care admission, and death

Meta-analysis: Lack of vitamin D is related to complicated COVID-19 infections, intensive care admission, and deathThe winter period is the time of year where we typically lack vitamin D, and this contributes to new waves of COVID-19 and other virus infections. Moreover, many older people, dark-skinned individuals, nursing home residents, and diabetics often suffer from chronic vitamin D deficiency which makes them much more vulnerable. Since the springe of 2020, numerous studies have demonstrated that lack of vitamin D increases the risk of COVID-19 infections, acute respiratory distress syndrome (ARDS), intensive care admission, and death. This is described in a new meta-analysis that is published in Frontiers in Public Health. Danish threshold levels for vitamin D in the blood are also too low, apparently. The question is: How much vitamin D do we really need?

A COVID-19 infection normally begins when a virus infects nasal cells and spreads to the lower airways. Most people are able to reject an infection or perhaps they only develop mild or moderate symptoms. However, if the immune defense does not function optimally, there is a risk of acute respiratory distress syndrome (ARDS). One major cause is a weak and derailed immune defense, which can result in hyperinflammation in the epithelial lining in the lungs. Hyperinflammation may also occur in the epithelial cells of blood vessels and in other organs, which can result in circulatory failure and – eventually – death.
Because COVID-19 is a coronavirus with a formidable ability to mutate, new variants of the virus constantly surface.

  • Coronavirus is a group of viruses that can cause disease in animals and humans
  • Coronavirus can cause colds, SARS (2002), MERS (2012), and COVID-19 (SARS-CoV-2)
  • Coronavirus is a so-called RNA virus that tends to mutate, which means new versions are constantly entering the stage
  • Vaccines therefore have a limited effect

Vitamin D is crucial for the immune defense for a number of reasons

Vitamin D is regarded as a steroid hormone that regulates a host of different genes by way of on-off switches. This is of vital importance to a well-functioning immune defense. In our respiratory tract, we have many white blood cells (macrophages) that need vitamin D to fight off germs and to communicate with the rest of the immune defense. The process is supported by antibiotic peptides in the airways that also depend on vitamin D. In addition, the immune system’s special troops in the blood – the T cells – need vitamin D to divide explosively, to attack virus, and to establish effective immunity. B cells that produce antibodies also need vitamin D.
A vitamin D deficiency causes large parts of our immune system to malfunction, making more vulnerable to infections. There is also a risk of poor communication between macrophages, which causes the immune defense to launch hyperinflammation that makes infections complicated and, in worst case, life-threatening.

  • Macrophages are a part of the innate immune defense and function as storm troops
  • Macrophages are also vital for the immune defense’s ability to communicate
  • A serious COVID-19 infection is a result of macrophage activation syndrome (MAS) where macrophages (subtypes) cause hyperinflammation and tissue damage

The greater the vitamin D deficiency, the greater the risk of COVID-19 infections, complications, and death

Numerous studies have revealed a link between blood levels of vitamin D in the form of 25-hydroxyvitamin D (25OHD) and an increased risk of COVID-19 turning into ARDS. The new meta-analysis aimed to investigate whether blood levels of vitamin D were somehow related to ARDS severity, including intensive care admission and death.
The authors collected data from PubMed, ScienceDirect, Web of Science, and other databases and ended up with 47 eligible studies, including 1,403,715 participants from different countries and with different racial backgrounds. Levels of vitamin D in the blood were categorized as:

  • Sufficiency: Over 75 nmol/L
  • Insufficiency: Under 75 nmol/L
  • Deficiency: Under 50 nmol/L
  • Severe deficiency: Under 25 nmol/L

It turned out that vitamin D levels below 75 nmol/L - defined as insufficiency, deficiency, and severe deficiency – were related to COVID-19 infections, related hospitalization, intensive care admission, and death. The meta-analysis supports an earlier meta-analysis that is published in Advanced Nutrients. It seems that the risk of a COVID-19 infection and related complications go up when then there is too little vitamin D in the blood. The Danish threshold level for vitamin D in the blood is 50 nmol/L. According to the new meta-analysis and many other studies, optimal values lie in the range of 75-125 nmol/L.

Vitamin D, supplementation, and requirements

The sun during the summer period is our major source of vitamin D because we only get limited amounts of the nutrient from our diet. The Danish Veterinary and Food Administration therefore recommends for everyone to take a supplement during the winter period, and vulnerable groups should supplement all year round.
In any case, it is essential to aim for optimal blood levels of vitamin D at all times. Our actual need for the nutrient depends on a number of factors such as sun exposure, age, skin type, BMI, and chronic disease.
EU’s Scientific Committee on Food has established a safe upper intake level for daily vitamin D consumption that is 100 micrograms for adults (including pregnant and breastfeeding women)
Vitamin D is lipid-soluble. Therefore, we get the best absorption and utilization by taking capsules with vitamin D in an oil solution.


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

Nurshad Ali. Role of vitamin D in preventing of COVID-19-infection, progression and severity. Journal of Infection and Public Health. 13 (2020)

Nihayet Bayraktar et al. Analysis of serum cytokine and protective vitamin D-levels in severe cases of COVID-19. Journal of Medical Virology 2021

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