Sunday, 1 November 2020

Covid-19 & Vitamin D : Santander & Heidelberg

Two more reports have been published that indicate the importance of low blood levels of vitamin D in determining death from Covid-19. 

It is vital to correct low blood levels of vitamin D.

Santander, Spain


Santander is a costal resort on the north coast of Spain, quite close to the border with France. It is a very pleasant resort and I have stayed there.

The study is snapshot observational and non-interventional. This means that low blood levels of vitamin D were not corrected.

It includes 216 hospital patients with Covid-19 infection and 197 community matched controls.

We can see (Figure 1) the blood levels of vitamin D in the Covid-19 hospital patients (blue) and the community controls who were well (green). It is clear that those with the very low blood levels (<10ng/ml) are mainly hospital patients with Covid-19. Correspondingly the higher blood levels (>20 and >30ng/ml) were found mainly in the healthy controls.  

Figure 1. Vitamin D levels in Covid-19 patients and controls

19 of the 216 patients were taking vitamin D before admission. These were analysed separately and details will be shown.

Hospital patients: mean Vitamin D level 13.8ng/ml 
Community controls: mean Vitamin D levels 20.9ng/ml

Figure 2. Vitamin D levels in Covid-19 patients and controls

A higher blood level of vitamin D appears to be of significant advantage, those with a lower level being ill and requiring admission to hospital (Figure 2).

The ideal blood level of vitamin D is greater than 30ng/ml (75nmol/L), as determined by several studies during the pandemic.  
It is perhaps surprising that blood levels of the community controls are so low, in a sunny place such as Santander.

47.2% of the community controls have blood levels less than the ideal 30ng/ml
82.2% of the hospital patients  have blood levels less than the ideal 30ng/ml
Hospital patients:
When admitted to hospital with Covid-19, there is a significant advantage of a higher vitamin D level in that it is associated with a lower need for transfer to ICU (Figure 3).

Vit D ≧ 20ng/ml  ICU required in 17.7%. 
Vit D < 20ng/ml  ICU required in 27.2%. 

Figure 3. Vitamin D levels and need for ICU transfer

Those with the higher blood levels of vitamin D, equal to or greater than 20ng/ml, had on average a shorter length of stay in hospital. (Figure 4)

Vitamin D ≧ 20ng/ml:  Days in hospital mean 8
Vitamin D < 20ng/ml:  Days in hospital mean 12

Figure 4. Vitamin D levels and length of stay in hospital

There was no difference in severity scores or deaths rates. 20 patients died, equally divided between groups  <10ng/ml and 10–20ng/ml.

Previous studies have indicated that a blood level of 30ng/ml is the threshold for high and low risk of death from Covid-19. It is unfortunate that the study did not divide the ≧ 20ng/ml group into two groups of 20–30 and >30ng/ml.

The effect of taking a vitamin D supplement.
There was a considerable benefit from taking a vitamin D supplement before the illness (Figure 5).

Covid-19 without Vitamin D supplement:
197 patients.
 50 (25.4%) needed ICU
 20 (10.4%) died

Covid-19 with Vit D supplement: 
19 patients
  1 (5.3%) needed ICU
  2 (10.5%) died.

Figure 5. Effect if vitamin D supplement on ICU transfer and death

This study shows more evidence that a good blood level of vitamin D and taking a supplement before the illness gives an advantage.

Heidelberg, Germany

Heidelberg Castle

This is a predictive non-interventional study of 185 hospital patients with Covid-10. 

Blood for vitamin D testing was taken on admission to hospital, but it was analysed only at the end of the study. This meant that the study was "blind", the investigators and the clinical staff having no knowledge of the blood levels of vitamin D of the patients. There was no vitamin D intervention and so the study design allowed predictive analysis.

185 patients in total.
 93 inpatients
 92 outpatients

The overall mean vitamin D level was 16.6 ng/ml (41.5nmol/L)
A blood level greater than 30ng/ml (75nmol/L) is regarded as ideal as judged by several other studies undertaken during the pandemic.

159 of the 185 patients (86%) had a blood level of vitamin D less than the ideal cut-off of 30ng/ml.

Figure 6. Blood levels of vitamin D in the Heidelberg study

Once again we see how common is vitamin D deficiency, but in this study there were no controls who were well. In patients with Covid-19 there is certainly an association with vitamin D deficiency, but more importantly blood levels of vitamin D predict the outcome.

The blood testing was taken at a relatively early stage in the illness, on admission to hospital.

The risks of ventilation and death are expressed as the hazard ratio. Ventilation and death rates of patients with low blood levels of vitamin D were compared to the ventilation and death rates of patients with blood levels >30ng/ml, who were given a standardised score of 1.

Hazard ratios for ICU ventilation:
Vitamin D >30ng  HR = 1.00 
Vitamin D <20ng  HR = 5.75 
Vitamin D <12ng  HR = 6.12

Hazard ratios for death:
Vitamin D >30ng  HR = 1.00
Vitamin D <20ng  HR = 11.27 
Vitamin D <12ng  HR = 14.73

Figure 7. Blood levels of vitamin D predicting need for ventilation and death

Having a blood vitamin D level of less than 12 ng/ml (30nmol/L) increased the risk of death by a factor 14.73. This is a reversible risk factor.

It is clear that in those with Covid-19 who require admission to hospital, a low blood level of vitamin D predicts a major risk of need for ventilation or death. I emphasise that this is a predictive study.

These two studies provide additional very strong evidence of the danger of a low blood level of vitamin D during the present pandemic of Covid-19.

I am of the opinion that predictive studies such as this must be brought to an end. With 18 positive published studies, we now have sufficient evidence of the benefits of vitamin D and the need to correct deficiency. 20 patients in the Heidelberg study died when they might not have done if they had been given appropriate vitamin D correction. We now need to minimise deaths by maximising defensive immunity.

Vitamin D deficiency and Covid-19 : its vital importance in a world pandemic

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  1. Once again, David, many thanks for your excellent work in the critical and graphic analysis of these two more studies. I absolutely agree that there is now sufficient direct and independent evidence to support what we both deemed to be obvious from the beginning from a host of previous studies with other infections. It should now be declared unethical to deliberately withhold vitamin D3 from anyone suspected of having Covid-19, and I believe this should also apply to anyone in a vaccine trial who falls sick. The whole emphasis in managing this pandemic should shift to providing vitamin D3 in adequate doses for the most vulnerable; people with dark skin, people confined indoors, and nursing home residents. And the adult dose should be not less than 4,000IU a day, or 100,000IU a month. And since it will do no harm, for a sick person 100,000IU should be given IM as a loading dose. The money to cover this new and urgent strategy can be taken from stopping useless PCR testing and tracing of well people.

    The D3 dose recommended by NHS England (400IU) is based on assumed needs of the endocrine system, which is by far the greediest consumer. There are countless tissues and systems that also depend on adequate reserves of D3, which the liver converts to the reserve/storage form (25(OH)D3) which all have to activate locally. Failure to recognise this is like a farmer deciding the amount of water going into in a communal water trough from the estimated needs of his greedy and aggressive bull, while forgetting all the lower profile and vulnerable cows. And we know that when 25(OH)D is activated to 1,25(OH)D locally in the immune system that is fighting off an acute infection, as with water from a communal trough, it cannot be recycled. Having acted, the active form is de-activated irreversibly to 1,24,25(OH)D3. So during an infection the blood level of 25(OH)D3 will fall if a decent supply is not sustained.

  2. David, thank you for this wonderful site on the benefits of vitamin D for health. It is an excellent source of information which I shall share with others.

    One slight correction, and this may surprise you and others. Santander, on the northern coast of Spain in Cantabria, is not, in fact, a particularly sunny location. It seems that this beautiful coastal resort only accumulates an average annual total of approximately 1649 hours of sunshine, very similar to London's yearly average. In fact, Eastbourne and other favoured spots on the south coast get considerably more sunshine, in the region of an average of 1900 hours of sunshine a year.