Tuesday, 14 April 2020

Vitamin D and Immunity – important against Covid-19

Vitamin D and Immunity – a brief introduction




Deaths from Covid-19 continue to increase worldwide. There is no immunisation; attempts at reducing numbers of cases and deaths by population isolation not seem to have a large effect in Europe.

The many trillions of virus copies cannot be destroyed. The way to protect the population from death is to maximise immunity and when necessary to provide intensive care life support.

I have drawn attention to three observations:
  • In the UK, six doctors, one nurse, and one health care assistant died from Covid-19. All were of black African or South Asian ethnicity. Shortly afterwards, on April 3rd 2020 a second nurse died, but she was white-skinned. However 8 out of 9 being of black African or South Asian ethnicity in the UK is more than a coincidence. 35% of those with Covid-19 requiring intensive care in the UK have black African or South Asian ethnicity. The USA has also experienced a proportionately higher risk of severe or fatal Covid-19 in BAME citizens. In Sweden it has been reported that 40% of Covid-19 deaths in Stockholm have been from the Somali community (<1% of the population). Skin pigmentation is obviously not itself the cause of the disease but it must be regarded as a very important susceptibility factor.
  • The greatest incidence of Corvid-19 cases and deaths in Europe has been in Northern Italy, which before the pandemic had the highest level of air pollution in Europe.
  • The pandemic of Covid-19 has occurred during the late winter in the northern hemisphere, and minor epidemics or clusters of viral "flu" always occurs at this time of the year (see EuroMomo)
All three are factors that are associated with low exposure to the sun and thus blood levels of  vitamin D: dark skin, air pollution, the winter.  Low blood levels of vitamin D will lead to poor defence against Covid-19. However it is reversible: if vitamin D deficiency is corrected in those at risk (which is effectively all of us in Europe, but especially those with dark skins) then there might be a reduction in the number of deaths.

It might be felt that this is supposition, but it has been established that vitamin D has an important role in immune defence mechanisms. It would be as well to look at this.

Vitamin D synthesis

Our skin, together with plankton living close to the surface of the oceans, are the most important sites of synthesis of the vitamin D that we need. Both produce initially the long-chain lipid squalene, also know as shark oil. The next stage is folding this molecule into the sterol 7-dehydrocholesterol (7-DHC). 

The critical part of the process, and a miracle accident of evolution, is that ultra-violet light of wavelength 270–300nm splits 7-DHC at a specific point, and as a result the molecule rotates and forms cholecalciferol, vitamin D. 






Three things can now happen. In humans the vitamin D (called cholecalciferol) which is synthesised in the skin enters the blood-stream. 

In furry animals the vitamin D is formed by UV light acting on the 7-dehydrocholesterol on the surface, in the oils that are secreted by the skin. Furry animals spend much time licking themselves and in this way they ingest the vitamin D, which is then absorbed from the intestine. 

The vitamin D in plankton enters the food chain via the plankton being eaten by small fish, and small fish being eaten by large fish, and large fish being eaten by humankind. The vitamin D is then absorbed by the intestine and it passes through the liver.

As the vitamin D passes through the liver it is activated by the addition of a hydroxyl (-OH) group to form calcidiol. Another hydroxyl group is added as the blood circulates though the kidneys to form the highly active hormone (chemical messenger) calcitriol.



Calitriol is a hormone that will activate vitamin D receptors (VDRs), protein enzymes found in cell walls. The calcitriol-VDR complex passes within the cytoplasm of the cell and reaches the cell nucleus. There it activates vitamin D responsive elements (VDRE) which can in turn activate a number of nuclear genes.




Response to infection

In response to infection, viral or bacterial, the body's defensive T-cells are activated as part of an enzyme cascade. This includes gene expression that stimulates further T-cell proliferation, and also increased synthesis of VDRs. As long as there is an adequate supply of vitamin D as calcitriol, there will be a feedback loop increasing the defensive immune response by a factor of up to 75.


The importance of vitamin D in defence against infection is clear, and it has been worked out in much greater cytogenetic detail than this brief sketch.

If you would like to see more detail, I would recommend:


Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)vitamin D: Genomic and non-genomic mechanisms
Haussler MR, Jurutka PW, Mizwicki,


https://www.ncbi.nlm.nih.gov/pubmed/21872797

(Not the easiest read.)

Another part of the pathway is that the defence cells macrophages ("big eaters") can themselves activate calcidiol to form calcitriol. This leads to the VDR-calcitriol complex enhancing gene expression via VDRE in the macrophage, and this further enhances immune defensive processes. Again, there must be a good supply of vitamin D to supply the substrate calcidiol.

Tuberculosis

The importance of vitamin D in defensive immunity was first recognised in observations of tuberculosis in the late 19th and early 20th centuries. 

The serious atmospheric pollution in the industrial cities of Europe led to the appearance of rickets, the childhood bone disease that is the direct result of vitamin D deficiency. This resulted from the failure of adequate penetration of sunlight through the polluted air to ground level. 

The movement of affected sick children to coastal fishing communities in Scotland and mountain-dwelling farming communities in Austria, and their consequent improvement,  led to the identification of vitamin D, which is obtained directly from the sun or indirectly from fish oil. However it was noted that rickets and tuberculosis frequently co-existed in families and communities, and that tuberculosis also improved on movement to an environment with clean air.

An interesting study undertaken in India and reported in 1922 demonstrated the close association between rickets and tuberculosis. However, unlike in Scotland, the families with these conditions were wealthy and it was the poor who were much more healthy. The poor spent all their time outside on the farms whereas the wealthy, and especially women and young children, were able to stay indoors and keep out of the sun.




Deaths from tuberculosis have declined dramatically but as we have seen in the late 20th century AIDS epidemic, tuberculosis becomes active when immunity is suppressed. Vitamin D deficiency is another form of acquired immuno-deficiency syndrome and is linked to activation of tuberculosis.. 

The reason for the decline in TB deaths is not clear, but it must have been due to an improvement in the resistance to the infection. This would be example of  "herd immunity", the spread of inherited immunity within the population. Additional factors would have been much-improved housing and nutrition towards the end of the 19th century. The provision of community parks and the opportunities for annual holidays to railway destinations would have helped improved sun exposure and vitamin D synthesis.











19 comments:

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  2. Bergamo is at the heart of the covid-19 crisis in Italy. It experienced the highest immigration in the 1970s from southern italy of any area in Italy. It has a large mediterranean population living at a northerly latitude. Vitamin D deficiency could be big factor.

    The stats are here:
    https://www.tandfonline.com/doi/full/10.1080/17421772.2010.540035

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  3. Actually Bergamo is no.2 and Bologna in Emilia-Romagna had the highest level of immigration from the south. it has 13% CFR and Lombardy has 18% (both very high)
    Confirmed 21,834
    Deaths 2,903

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