Covid-19 & Vitamin D: Evidence from Tameside, Milan, Wuhan

Ashton – Peak Forest canal junction, Tameside

More evidence is now available to demonstrate the advantages of vitamin D if developing Covid-19. It is all positive in favour of vitamin D, with no evidence to the contrary.

There are now to my knowledge 21 reported studies indicating the dangers of low blood levels of vitamin D and the advantages of supplements. The three most recent are shown here.

Tameside, NW England

"Vitamin D treatment is associated with a reduced risk of mortality in patients with Covid-19".

This is from a pre-print of a paper that will appear in The Lancet.

[This pre-print link is not currently active. The main author tells me that the paper is being rewritten]

A prospective study of 986 subjects was undertaken in England, based in Ashton under Lyne, Tameside (to the east of Manchester), and including hospitals in Preston and Leicester. The study was of patients admitted to hospital on account of proven Covid-19 infection. The blood for vitamin D testing was taken on admission, and so this was a predictive study of vitamin D in the course Covid-19 infection. No intervention was given. However some of the patients had been taking a vitamin D supplement before admission, and they were analysed separately.

The conclusion of the study is in the title: "Vitamin D treatment is associated with a reduced risk of mortality in patients with Covid-19".

And so it was. Those patients previously taking a vitamin D supplement had just half the risk of death.

A wide range of parameters were measured in this study, and the results can be summarised in Figure 1.

Figure 1. Odds ratio of death. Log scale, 1 = average, less than one an advantage, greater than one a disadvantage.

As predictors of death, an advantage was seen in those on vitamin D treatment (supplement), and also those with a history of asthma, an observation without a clear explanation.

Disadvantages were age >74, the need for high-flow oxygen, a history of heart disease, low oxygen levels in the blood, high C-reactive protein (cytokine marker), high creatinine (indicating kidney damage), and female. Generally these are predictable, but not the slight excess risk of females.

There were three groups of vitamin D reported:

 >20ng/ml.   >50 nmol/L

10–20ng/ml. 25–50 nmol/L 

<10ng/ml.  <25 nmol/L 

This is the weakness of the study. It would have been of great advantage to create four groups, so as to identify:

>30ng/ml. >75 nmol/L 

20–30ng/ml. 50–75 nmol/L 

10–20ng/ml. 25–50 nmol/L 

<10ng/ml.  <25 nmol/L 

It would not have been known in the early part of the year when this study was defined, but other studies during the pandemic have demonstrated that a blood level of >30ng/ml. >75 nmol/L marks the transition between high risk and low risk, with a rapid change, a watershed. This is shown in Figure 2. Defining 20ng/ml (30nmol/L) as "normal" (or "replete" as in the Tameside paper) is wrong as it can be seen that it is associated with a relatively high risk of death. It is is far from the ideal of >30ng/ml (75nmol/L), and it is ideal that should be the objective.

Figure 2. Death rate from Covid-19 based on blood levels of vitamin D. 

A dramatic diminution of death risk above 30ng/ml is obvious

It is for this reason that the results of vitamin blood levels in this paper are disappointing.

In Figure 3 we can see the distribution of blood levels of vitamin D in the 953 subjects tested. 75% had blood levels of less than 20ng/ml (50nmol/L), that is they were deficient. Of the remaining 25%, we are not informed of the proportion with an ideal blood level of >30ng/ml (75nmol/L). It might have been less than 10%. This indicates a major public health challenge.

            Figure 3. Distribution of blood levels of 953 subjects

There was an assessment of the blood level of vitamin D related to the need for intubation / ventilation on the ICU. The odds ratio was 1.83 for patients with a low vitamin D blood level of less than 20ng/ml (<50nmol/L). This is an increased risk, almost double the average in the study.

For those with a blood level greater than 20ng/ml (50nmol/L) the risk of ventilation was below average, about half average, with odds ratio 0.55.   

This is shown in Figure 4, again a log scale showing odds ratio. 

Figure 4. Odds ratio of need for ventilation / ICU

The lower, reduced, risk of ventilation / ICU is in those with blood vitamin D levels greater than 20ng/ml (50nmol/L). Once again a low level of vitamin D increases the risk of intensive care ventilation and a high level is much safer,

We also observe that 75% of those investigated were deficient in vitamin D. There is need for public health action.

Milan, Italy

Low vitamin D levels independently associated with severe COVID-19 cases and death.

A study was undertaken of 103 severely ill patients admitted to the San Luca Hospital, Milan, COVID-19 unit between March 9 and April 30, 2020. Blood was taken on admission for testing including levels of vitamin D as 25(OH)D and the study was to observe subsequent progress.

This was therefore a predictive study. There was no vitamin D intervention.

They were compared with 52 patients with Covid-19 but with either no symptoms or very mild symptoms, and also with 205 community matched controls who had recently had blood vitamin D testing as routine health assessment.

The results were as follows

Of the 103 severely ill patients, the mean blood level of vitamin D was 18.2ng/ml (44nmol/L) compared to the control group in whom the mean level was 25.4ng/ml (62nmol/L).

Of those who were severely ill and required admission to ICU the mean blood vitamin D level was 14.4ng/ml (29nmol/L), compared to 22.4ng/ml (56nmol/L) in those who did not require ICU admission.

19 (18.44%) died and their mean blood level of vitamin D was 13.2ng/ml (33nmol/L).

35 survived and they had a mean blood vitamin D level 19.3 ng/ml (48.25nmol/L).

Those with mild disease had a mean blood vitamin D level of 30ng/ml (75nmol/L).

The controls, assumed to represent the national average, had mean blood vitamin level 25.4ng/ml (63nmol/L).

Figure 5. Outcome from COVID-19 based on blood levels of
vitamin D on admission

This study was presented by Professor Luigi Gennari MD of the University of Siena in Italy, at the American Society for Bone and Mineral Research virtual meeting, September 11th 2020.

Wuhan, China

The report was published in the Journal of Nutrition on November 13th 2020.

The study involve 335 consecutive patients admitted to Tongji Hospital, Wuhan, in March 2020 on account of Covid-19. Six of the patients died. All had vitamin D blood levels performed on admission to hospital. There was not vitamin D intervention.

The study also involved 560 matched controls from a database of 22,397 from a recent community examination program.

Results

Vitamin D, mean:

Controls 13.0ng/ml, 32.5nmol/L

Patients 10.6ng/ml, 26.5nmol/L

Deficient = <12ng/ml, <30nmol/L

controls 40.7%, patients 65.7%

Risk of severe disease:

Odds ration 2.72 for those deficient compared with non-deficient

Deaths:

Vitamin D mean = 7.48ng/ml, 18.7nmol/L

Figure 6. Vitamin D and outcome, ng/ml

Figure 7. Vitamin D and outcome, nmol/L

We see a lower blood level of vitamin D in Covid-19 hospital patients compared to controls and the lowest levels associated with severe illness, and in particular with death.

The study gives the opinion that vitamin D deficiency is a global public health concern.

The blood levels of vitamin D are remarkably low compared to studies in Europe. This is likely to be the result of the extremely serious atmospheric pollution for which Wuhan is known, the pollution preventing UV from the sun penetrating to ground level, and thereby vitamin D production is inhibited. The other factor is possible sun-avoiding behaviour of the population. Vitamin D deficiency certainly appears to be a serious problem in Wuhan.

In this study, deficiency of vitamin D was defined as less than 12ng/ml (30nmol/L), and "non-deficient" as greater than this level. It is more usual for 20ng/ml (50nmol/L) to be the boundary between deficient and non-deficient. Other studies undertaken during the pandemic demonstrate that a blood vitamin D level greater than 30ng/ml (75nmol/L) can be judged as safe from significant risk of unfavourable or fatal outcome from Covid-19. 

Conclusion

It is clear once again that low blood levels of vitamin D predict critical disease and fatal outcome from Covid-19 infection. 

This has now been demonstrated on many occasions. If there is a desire to reduce ICU admissions and deaths from Covid-19 it would seem to be sensible to correct the widespread low levels, that is deficiency, of vitamin D in the community. It is so obvious and so simple. It is beyond belief that it has not yet been done, despite the UK having now experienced more than 50,000 deaths from Covid-19.

https://www.ypdbooks.com/2147-vitamin-d-deficiency-and-covid-19-its-central-role-in-a-world-pandemic-YPD02419.html