Monday, 28 December 2020

Covid-19 & Vitamin D : at the end of 2020

 At the end of 2020


This time a year ago we had no idea what was ahead of us in 2020. After hearing of a new virus in Wuhan, we initially thought that it had been contained by the Chinese authorities. However although Wuhan was isolated within China, the airport was not closed to international travel. The virus spread around the world and reached the UK by air transport. By early April there were  5,000 cases of Covid-19.

By March 23rd there had been 258 deaths. The situation was serious and so the government introduced "lockdown" in an attempt to stop the spread of the virus by using physical means. The success was doubtful, as shown by subsequent events.

Controlling a water-borne infection (usually a bacterium) is possible by the physical process of separating waste from the water supply and purifying the water. Contagious (touching) diseases can be controlled by isolation, but controlling an invisible respiratory virus such as Covid-19 that travels through the air is different. Physical control might have been possible had the first two cases, in York, been totally isolated, but after failing to do so (for reasons that are perfectly understandable) travel took over and the virus spread. Control of the spread of the virus was always going to be impossible and so it has turned out to be. Of greatest importance should have been to minimise the impact of the virus on the human host.

There was at the beginning of 2020 ample medical-scientific knowledge that the most promising way in which to control the impact of the virus on the population would be to correct as quickly as possible the known wide-spread deficiency of vitamin D, knowing that vitamin D has a vital role in activating defensive immunity. This knowledge appears to have been unknown to SAGE, our not-so illustrious Scientific Advisory Group for Emergencies. The potential of vitamin D was ignored and was not used – with one exception. Although vitamin D silence was maintained by his advisors, in November the government Health Secretary Matt Hancock announced that vitamin D supplements would be supplied to the vulnerable residents of care homes. Unfortunately this initiative appeared to be in a setting that would not include research, the advancement of science.

The "first wave" of Covid-19 settled as we moved into the Spring and Summer of 2020. With the onset of Autumn and Winter, a "second wave" occurred, as was predictable. In reality there was just one wave and it was interrupted by nature during the Summer months.

We need to look the pattern that we experienced during 2020. 

Figure 1 shows deaths per day. By March 23rd there had been 258 deaths and lockdown was introduced. The effect was hardly dramatic and by early April Covid-19 deaths had reached 1,000 per day. The pattern shows that the decline in deaths occurred in mid-April, at the time that the sun was high enough above the horizon (more than 45 degrees) so that the UV intensity became sufficient to produce vitamin D in our skin. Defensive immunity was thereby activated. The decline of deaths continued and was virtually abolished by August, when blood levels of vitamin D would be highest. 


Figure 1: UK Covid-19 deaths per day

The body would have built up reserves of vitamin D, and so there was a delay after the Autumn solstice before the daily deaths started to increase, but inevitably they would do so. This is the annual pattern not just of Covid-19 but other infections and also all-cause mortality. It shows the power of the sun in controlling life and death on Earth, not just food production but also defensive immunity. It is difficult to think of an explanation for this pattern other than the sun. It might be suggested that air temperature might be the mechanism rather than or in addition to vitamin D production. However humankind is isothermal, and this annual pattern is seen throughout the temperate zones of the northern hemisphere irrespective of air temperature.

Figure 2 shows the number of Covid-19 cases per day. There have been many more cases at the end of the year than at the beginning as testing had become much more extensive. 

Figure 2: UK new Covid-19 cases per day

Once again we can see the suppressant effect of the sun producing defensive vitamin D, and the rise in cases when summer reserves are exhausted. In the northern hemisphere where many millions live closer to the north pole that to the equator, serious vitamin D deficiency becomes very common during the winter months.

We anticipate that the same pattern will occur during 2021, but with reduced numbers of cases and deaths. Herd immunity is developing and will improve with widespread vaccination, more so if vitamin D supplementation is also brought into use. The April–May decline will of course be attributed to the effect of the vaccine and as usual the benefit of nature will be ignored. “The art of medicine consists of amusing the patient while nature cures the disease.” (Voltaire)

The same pattern of Covid-19 deaths can be seen in other European countries, and in Canada at a similar latitude.

Figure 3: Covid-19 deaths in Germany


Figure 4: Covid-19 deaths in Netherlands


Figure 5: Covid-19 deaths in Austria



Figure 6: Covid-19 deaths in Canada

The pattern is clear and obvious. Vitamin D produced in the skin by the action of solar UV brings about a remarkable enhancement of immunity and thereby suppresses the impact of infection. Deaths are diminished by 100 or more day. 

We can also look back on 2020 to see the relative impact of Covid-19 in various countries. This is achieved by looking at cases and deaths per million population.

Figure 7 demonstrates cumulative number of cases per million in selected countries, mainly European.  The horizontal dotted line indicates the UK, just over 30,000 cases per million. 

Figure 7: Covid-19 deaths per million

The UK level is high but not exceptional.  

Figure 8 shows Covid-19 deaths per million, again the UK level being indicated.

Figure 8: Covid-19 deaths per million


We can see that in respect of deaths the UK is among those with the highest death rates, 
disproportionately high compared to cases per million.

Conclusions

It is these careful observations that lead me to the conclusion that what we have been doing is inadequate, and that the number of deaths is not acceptable. We need an additional line of action to control the impact of the pandemic. This is available now and it is vitamin D, or for the seriously ill Calcifediol, its part-activated form that is effective immediately. So far it has been officially ignored

The fact that vitamin D has not been used officially in the UK is the result of unacceptable ignorance at high levels, and a stubborn resistance to learning. No doubt after 70,000 deaths, for the senior culprits to acknowledge the value of vitamin D would mean great humility and "loss of face", characteristics that are uncommon is such people. But humility is a great strength, and the recognition of ignorance is the first step in learning.

In previous posts we have seen the remarkable benefits of Calcifediol in the treatment of Covid-19 pneumonia. The controlled trial was undertaken in Córdoba, a city in the Spanish province of Andalucía and demonstrated 96% efficacy. Vitamin D was brought into wider use in late November, mainly to the residents of care homes for the vulnerable elderly. The benefits are seen in the daily death statistics, as shown in Figure 9.

Figure 9 : Covid-19 deaths per day in Andalucía. )Fallecidos = deaths)
Vitamin D issued in late November



Once again we can see the dramatic benefit of the sun during the summer months. In addition we can see the equally dramatic effect of vitamin D supplementation given in late November. Daily deaths have fallen from 50 per day to two per day. We should learn from Andalucía.

This is another example of the benefit of vitamin D that no doubt our leaders will choose to ignore.

NICE will no doubt continue to express the view and recommendation:

"Still not enough evidence to use vitamin D at this time." 

Basically "at this time" this means that 2 million cases and 70,000 deaths are not of great importance, that there is still no need for the demonstrated benefits of vitamin D to be considered to be useful. 

"...at this time" now also includes the time that a mutation variant of Covid-19 is particularly threatening. The activity of the various vaccines against this and other mutations is unknown. What is clear however is that optimisation of defensive immunity is now more important, as this is expected to protect us against all mutations of Covid-19. The need for correction of vitamin D deficiency is greater than ever.

NICE recommendations are recommendations and not directives. The NHS and public health bodies in all nations have the responsibility to make policy decisions, and an evaluation body such as NICE can only advise decision-making and must not have executive authority.

There remains the opportunity for individual initiatives in individual hospitals or other settings. Let us hope that initiatives occur.





Saturday, 19 December 2020

Covid–19 and Vitamin D: Efficacy of vaccines

Efficacy of Covid-19 vaccines


This Blog post might be a bit dull, but it contains information about the performance of the three new vaccines, which are about to be introduced.

First a reminder of Cacifediol

Calcifediol / vitamin D 



We have seen that vitamin D in its rapid-acting part-activated form Calcifediol is remarkably effective the treatment of Covid-19 pneumonia. We have seen that its efficacy is 96%, and also how this is worked out. 

Proportionate benefit = efficacy = 96%

Absolute benefit = 48%

NNT = 2, meaning that 2 treatment are necessary to prevent 1 ICU admission/death.

In the control group 2 deaths occurred among the 13 patients needing admission to the ICU.

We have also seen that the cost of preventing an ICU admission or death would be approximately £10. 

We have also seen that a detailed report from Massachusetts Institute of Technology indicated that the  Córdoba RCT of Calcifediol was conducted properly, and that the probability of the positive result being by chance is less than one in a million.

We have seen that the study was rubbished by NICE and as a result it has not been used in the UK. It is likely that since the trial's results were published on September 3rd, 25,500 UK citizens have died from Covid-19. This would have been a much smaller number if the results of the Córdoba study had been put into action, and hospital patients with Covid-19 pneumonia treated with Calcifediol.

Physical or immunological protection?

The government and its advisors have done a great deal in what can only be described as a futile attempt to conquer the air-borne respiratory virus by physical means. It was clear from the outset to people with a knowledge of biological science that the most important approach would be to protect our citizens by mechanisms of immunity.

There would be two approaches to this. One would be to develop a vaccine but that would obviously take time. The vaccines are becoming ready for use at the end of 2020, by when more than 65,000 deaths from Covid-19 will have occurred in the UK. There are still some concerns about vaccine safety.

The other approach would be to optimise innate defensive immunity, and this is best undertaken by correcting widespread vitamin D deficiency. Even before the pandemic developed, it was or should have been well-known in medical–scientific circles that vitamin D is the vital key that unlocks the enhancement of the defensive immune process. 

On March 23rd 2020 there had been 285 deaths from Covid-19 in the UK. Lockdown was introduced, with huge social and economic cost. Vaccines were well in the distance, but vitamin D could have been and should have been used to help defend the people while waiting for a safe vaccine to be produced.

The vaccines are now available or are being tested. It is known that in the presence of vitamin D deficiency, vaccines are less likely to produce an immune response.

I have used prices of vaccines that I have seen. More accurate or dependable prices might become available, and can then be substituted.

Pfizer vaccine



The Pfizer trial, 1st release “90% effective”


Pfizer released this data to the press.


36,995 subjects recruited into the trial, divided into two equal sized groups 18,497 in each (forget the one extra for now as we were not told which group this person was in).

Placebo 85 cases, no deaths

Vaccine 9 cases, no deaths


This is all the data that we have been given. 

What it means is this:

Reduction of cases in the vaccination group is 85 (control) minus 9 (vaccine), equals 76.


Efficacy method 

Expected number of deaths in vaccine group =

number of deaths in placebo group = 85

Observed number in vaccine group = 9

Cases prevented by vaccine = 85 - 9 = 76 

76 prevented out of 85 = (76/85)x100 = 89.411 %

Proportionate reduction of cases = Efficacy = 90%


Absolute benefit

Control group : 85 cases out of 18477 = 0.46%

Vaccine group:   9 cases out of 18477 = 0.049%

Gain from vaccine = 0.46 - 0.049 = 0.41%

Absolute risk reduction of cases = 0.41%

 

Number needed to treat

18,497 vaccinations are necessary to prevent (85 - 9) = 76 “cases” (whatever a case might be). 

18497 ÷ 76 

= 243 vaccines are necessary to prevent one case

243 is the NNT, the number needed to treat to prevent one case.


From this we can calculate the cost of one case prevented, on the basis that the cost of one success must be the sum of the NNT.


Cost

We are told that the price of one vaccination (assume a pair of vaccinations in one person) is $20. We assume that this includes distribution and storage costs.

We are told that in the UK there will be a £12.85 ($17.19) doctor administration fee. I will ignore this in the calculations but it will almost double the costs of vaccination.

Cost = $20

NNT 243 x $20 = 

$4,860  the cost per case prevented. 

Some people would rather have the money.


Deaths prevented (prediction only)

World wide there are 50 times more cases than deaths, ratio of cases to deaths is 50:1. 

This means that to prevent one death will require:

 243 x 50 = 12,156 vaccinations. 


This will result in a cost of 

50 x $4,860  

= $243,000 to prevent one death. 


My family would perhaps rather have the money!

Remember that most deaths are after the age of 80, with life expectancy about ten years =

$24,300 per year gained (quality not considered). 


In the UK the ratio of cases to deaths is 25:1

This means that cost per death prevented is half the worldwide average

243 x 25 = 6981 vaccinations to prevent one death = $139,620.



Pfizer trial, 2nd release “95% effective”

43,000 subjects, assumed equally divided.

21,500 placebo, 162 cases

21,500 vaccine, 8 cases


Vaccine group

Expected cases = 162

Observed cases = 8

benefit: (162 - 8) = 154


Cases prevented = 154 out of 162

= (154 ÷ 162) x 100 = 95%


Efficacy = 95%


21,500 vaccinations prevented 154 cases

(21,500 ÷ 154) = 140 = vaccinations to prevent one case

140 x $20 per vaccination 

= $ 2,800 per case prevented

= $ 140,000 per death prevented (world average)


Absolute benefit

Control group : 162 cases out of 21500 = 0.753%

Vaccine group:    8 cases out of 21500 = 0.037%

Gain from vaccine = 0.753 - 0.037 = 0.716%

Absolute risk reduction of cases = 0.72%

This does not sound quite so good, and so proportionate reduction of cases in expressed rather than absolute.

Moderna vaccine



The publication process is very slow. 

On November 12th a paper was published in the New England Journal of Medicine with he results of a phase 1 study involving 45 subjects receiving the mRNA-1273 Covid-19 vaccine. It had appeared as a pre-print on July 14th. The purpose was to define optimal dose.


https://www.nejm.org/doi/full/10.1056/nejmoa2022483


The results of the clinical trial were released to the press in advance of peer-reviewed publication, and appeared in New Scientist on November 16th.


https://www.newscientist.com/article/2259939-moderna-coronavirus-vaccine-trial-produces-best-results-yet/#ixzz6gS693gbk

Headline:
The Moderna mRNA-1273 vaccine seems to be 95 per cent effective and to work in those who need protecting the most – people aged over 65 

This is an "interim analysis", but the result is to bring the Moderna vaccine into use.

More than 30,000 people in the US aged 18 and over are taking part in the phase III trial of the Moderna vaccine.
Assume 15,000 in each group, placebo and active vaccination.
Placebo 90 cases (15 severe)
Vaccine group 5 cases (none severe)

Vaccine group, 90 expected, 5 observed.
Reduction of cases = 90-5 = 85
Reduction is 85 out of 90
= (85 ÷ 90) x 100 = 94.44 = 95% approx.

Absolute risk reduction
Risk of infection:
Placebo group:  90 out of 15,000 = 0.6%
Vaccine group :  5  out of 15,000 = 0.33%
Risk reduction = 0.6 - 0.33 = 0.47%

Number needed to Treat
15,000 ÷ 85 = 176
NNT = 176. 
176 vaccinations needed to prevent one case.

Price of Moderna vaccine: $10 to $50 per dose.
If $10 per dose, $1760 to prevent one case
If $50 per dose, $ 8750 to prevent one case. 

Cost of one death prevented (case x 50) = 
$88,000 or $437,500

Prices of vaccines
https://observer.com/2020/11/covid19-vaccine-price-pfizer-moderna-astrazeneca-oxford/

AstraZeneca vaccine


https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

Different dosage groups, in UK and Brazil
One example:

Low Dose + Standard Dose
Vaccine: 1367 subjects, 3 cases
Placebo : 1374 subjects, 30 cases
Cases prevented = 30 - 3 = 27
27 cases prevented out of 30 = 90% efficacy

Number Needed to Treat
1367 vaccinations to prevent 27 cases
= 51 vaccinations to prevent 1 case
NNT = 51

Price $4 per dose
Cost per case prevented = $4 x 51= $204
Cost per death prevented = $204 x 50 = $10,200

Standard Dose + Standard Dose
Vaccine: 1879 subjects, 14 cases
Placebo : 1922 subjects, 35 cases
Cases prevented = 35-14 = 21
21 cases prevented out of 35 = 60%

Number Needed to Treat
1879 vaccinations to prevent 21 cases
= 89 vaccinations to prevent 1 case
NNT = 89

Price $4 per dose
Cost per case prevented = $4 x 89 = $356

Cost per death prevented = $356 x 50 = $17,800


No conclusions, just observations.

Vitamin D and vaccines are complementary.

Giving vitamin D now would reduce the impact of the Covid-19 pandemic before the vaccines are widely used. Also vitamin D is necessary to activate the immune system so as to allow the vaccine to induce a good response. 

Also vitamin D is available now and distribution costs are minimal. There are no costs of storage or administration. Safety is not a concern in the doses recommended (up to 4,000 units daily or equivalent).

Vaccines will not be of help to those who are ill from Covid-19. For this, Calcifediol the part-activated  form of vitamin D is essential.






Tuesday, 8 December 2020

Covid-19 & Vitamin D: Calcifediol has 96% Efficacy and very low cost




£10 to prevent ICU admission or death

Updated December 15th


We are moving forward in respect of both prevention and treatment of Covid-19. Action is needed, as in the UK we have had 60,000 deaths attributed to Covid-19.  There have been more than 1.6 million cases, but it never clear what a "case" means. Even deaths are not clear, and it is always stated on news broadcasts that "There have been 500 [or whatever number] deaths today in people who have tested positive for Covid-19 during the past 28 days". Road Traffic Accidents perhaps?

In the UK there have been approximately 25x more cases than deaths, whereas internationally it is 50x more cases than deaths. The geography of Covid-19 is another story, but the UK is not doing well. We have now reached in excess of 900 deaths per million, among the highest in the world.



How good have our interventions been? We cannot have confidence in our physical policies of distancing, closure of schools, universities, places of worship, workplaces, restaurants, sports venues, social occasions including weddings and funerals, family contacts etc. There has been a huge social and economic price to pay for little if any gain.

An immunological approach has always held more promise, with massive investment in the production of vaccines. However there has been complete neglect by governments of correcting wide-spread vitamin D deficiency. This is despite the knowledge that vitamin D is essential for unlocking defensive immunity, and ignoring several research observations of the bad outcome and death from Covid-19 in those deficient.

I will look at vaccines next time, but for today I will keep to vitamin D to explain how "efficacy" is worked out.


Córdoba, Spain

I have described in previous posts the powerful trial from Córdoba concerning the hospital treatment of patients with Covid-19 pneumonia. The study used the rapidly-acting part-activated form of vitamin D, namely Calcifediol, or 25(OH)D, a natural product. We have seen the pathetic superficial rubbishing by the UK National Institute of Health and Care Excellence (NICE), with instruction not to use Calcifediol. In contrast a detailed analysis at the Massachusetts Institute of Technology (MIT) identified no procedural fault and a less than 1 in a million probability of the positive result being due to chance.

I would like to analyse the results of the Córdoba study to assess the efficacy and economic value of Calcifediol. 

There were 76 patients in the study, all admitted to hospital on account of Covid-19 pneumonia. They were randomised into two groups, 2:1 ratio treatment:control. Treatment was started on admission to hospital with standard high quality care with or without Calcifediol. The main outcome end-points were the need for admission to ICU and death.

Calculation of Efficacy

Placebo control group of 26 patients: 

13 ICU transfers = 50% ICU transfer rate, 2 deaths


Calcifediol 50 patients:

Expected ICU transfers would be, from control group,  

50% of 50 = 25

Observed ICU transfer was 1


Therefore ICU transfers prevented by treatment were 

25 (expected) -1 (observed) = 24

24 out of 25 ICU transfers = 96 out of 100

Efficacy = 96%


Absolute or proportionate benefit

The reduction of ICU transfers was 50% to 2%

50% - 2% = 48% absolute benefit from Calcifediol


And for the usual amplifying spin:

48% of 50%

(48 x 100) / 50 = 96% proportionate benefit from Calcifediol



Calculation of NNT

In the Calcifediol treated group of 50  

1 ICU transfer = 2% ICU transfer rate


50 patients treated with Calcifediol reduced ICU transfers by

 

25 expected - 1 observed = 24


50 Calcifediol treatments to prevent 24 ICU transfers

50 ÷ 24 = 2 patients needed to be treated to prevent 

1 ICU transfer


number needed to treat to prevent on endpoint of ICU transfer

NNT = 2


Cost–benefit analysis   Updated December 15th

The principle is that the cost of all the patients treated must be borne by the ones who benefit. Therefore with an NNT of two, the cost of twor treatments is the cost of preventing 1 ICU transfer

= 2 x cost of one course of Calcifediol


In Spain the price charged for Calcifediol is €10.32 for 10 softgels each containing Calcifediol 266 micrograms.

In the Córdoba RCT and on the package show, the dose is expressed as 0.266mg. Decimal points can be confusing and so the dose is better written as 266 micrograms, using full text for micrograms as abbreviations can also be confusing.


The course of treatment is:

day 1, 532 micrograms

day 3, 266 micrograms

day 7, 266 micrograms

day 14, 266 micrograms

This is 5 soft gels, a total cost of €5.16, £4.68, $6.27

The cost of one ICU transfer or one death prevented 

= NNT x €5.16

=    2    x €10.32

=  €11.32,  £9.36,  $12.53


Treatment with Calcifediol will result in substantial savings of money as well as deaths. One day on an ICU cost approximately £2,000.


What about deaths prevented?

In the control group there were 2 deaths, all in the ICU.

In the Calcifediol group there ware no deaths.

2 versus 0 does not lend itself to statistical calculation.We cannot assume a 100% reduction in deaths.

There was a 96% efficacy in the reduction of ICU transfer and the must have been an  efficacy in the reduction of deaths greater than 96%.


Covid-19 Vaccines


Analysis will follow in the next post.

















Sunday, 29 November 2020

Covid-19 & Vitamin D. Calcifediol – Report from Massachusetts Institute of Technology

MIT 1, NICE 0


Massachusetts Institute of Technology

The results of the randomised controlled trial from Córdoba, Spain, came to attention on September 2nd 2020. It showed a resounding success of the treatment of Covid-19 pneumonia using Calcifediol (25(OH)D), the natural part-activated form of vitamin D.


Córdoba RCT

Controls: 

26 patients, standard high quality treatment only. 

13 (50%) required transfer to ICU, two died.

Calcifediol treated group:

50 patients, standard high quality treatment + immediate Calcifediol.

1 (2%) required transfer to ICU, no deaths.

This means that compared to the control group, we would have expected 25 (50% of 50) patients in the Calcifediol treatment group to require transfer to ICU, but this was reduced to 1. 

24 out of 25 reduction is a 96% reduction, (24/25)x100. This is 96% efficacy.


Response from NICE

I have indicated in a previous post that this study from Córdoba was rubbished by the UK National Institute for Health and Care Excellence (NICE) in a report of September 20th.  The commentary was provided by Professor Neil Gittoes, Consultant, Honorary Professor of Endocrinology and Associate Medical Director, University Hospitals Birmingham NHS Foundation Trust; Chair of NHS England specialised endocrinology Clinical Reference Group. 

The basis of his report was a series conjectures rather than research.

But it was very effective and the instruction issued to medical staff by NICE was:

"The clinical management of patients with COVID-19 should not be changed based on the results of this study."

This instruction has been followed. It appears that Calcifediol has not been used in the UK. Since September 2nd, more than 16,000 people have died from Covid-19 in the UK, and ICUs are reported as being overwhelmed. 

In Switzerland, it has been reported that doctors are recommending that vulnerable people over the age of 60 years, with heart disease or diabetes should sign "Do not Resuscitate" orders so that the ICUs can cope with fewer patients (Times, November 23rd). 

Even today the demonstrated benefit of vitamin D as Calcifediol has remained unused.


Analysis by MIT


The world or its medical-scientific advisors appear to going mad, or are seriously negligent. But not the scientists of the Massachusetts Institute of Technology (MIT).

A major analysis of the Córdoba study has been undertaken at the MIT and it came to my attention when I was watching an interview of David Davis MP, one of our very few scientifically trained members of parliament. He has realised the vital importance of vitamin D deficiency in this pandemic and he is struggling to stir the government and the nation into action.

The MIT analysis is one of great detail, and it puts to shame the cursory approach of NICE. It researched the conduct of the study as well as analysing its results.

The conclusion (of MIT analysis) is that there was no fault in the conduct of the Córdoba trial. It acknowledged that the findings (as above) are robust, and that the chance of the results being in error is less than 1 in 60,000. 

The paper from MIT contains a lot of statistical maths but the message is stated clearly for those inclined to read it. 

Has the MIT report been read by NICE? Is NICE going to respond? Is NICE going to allow medical staff to use Calcifediol in patients seriously ill with Covid-19? Are patients with Covid-19 going to continue to transferred to ICUs in overwhelming numbers? Are people still going to die when they need not?


Is there sufficient Calcifediol

The RCT is being continued in Andalusia, Spain, in a total of five hospitals. Results are due soon and I hear unofficially that Calcifediol has resulted in a 50% reduction of deaths. If the result is so positive there will be no defence in not giving Calcifediol at least to hospital patients with Covid-19 pneumonia. Is there any defence now? 

A problem will be the availability of Calcifediol. I hope that the government has the wisdom to obtain large supplies of Calcifediol so as to meet a sudden large demand. 

There are several manufacturers of Calcifediol, in China, Korea, India, Netherlands, USA. Most of it used as animal feed, as though we care more about cattle than about humankind.

I can find from a USA website that the cost of Calcifediol is $200 for a 200mcg dose. The dose regimes from Córdoba is 532mcg on admission, 266mcg on days 3, 7, 14 and perhaps 21,28. This appears to be about $200 x 5 = $1,000. In 2003 the cost of one day in an ICU was $1364, likely to be greater now. In the Córdoba RCT the result was a reduction of need for ICU transfer by 96%, a major saving with the cost of Calcifediol being very good value for money.  


Sao Paulo, Brazil

An RCT in Brazil investigated giving natural rather than activated vitamin D in an attempt to reduce length of stay of 240 hospital patients admitted with Covid-19 pneumonia. 

They were all given standard care but randomly allocated to receive either a single oral dose of vitamin D 200,000 units or a placebo.

The outcome was no difference between the two groups in respect of length of stay, need for ventilation, or death. In those who received the vitamin D supplement the blood level rose, but the the time sequence was not displayed.


What about Vitamin D?

Vitamin D gave no advantage in the Brazil study.

Although this can be regarded as a disappointment to those like me who feel that vitamin D has a great therapeutic potential, perhaps the importance is that of timing.

When we measure the blood level of vitamin D we measure it as its 25-hydroxylated form 25(OH)D, which is Calcifediol. The part-activation process by hydroxylation takes place in the liver, but is rather slow and leisurely. This is fine in general life when are just trying to maintain a steady blood level. 

We can see from Figure 1 that for people who are deficient in vitamin D, less than 10ng/ml (25nmol/L), a range of supplement regimens  take up to two weeks to increase the blood level above 30ng/ml (75nmol/L, the safe range. Two weeks is much too slow to help a patient who is critically ill with Covid-19 pneumonia, but is adequate for correcting deficiency in a well person.



Figure 1. Response to vitamin D by mouth, in black is the average of three regimens.  In red is 100,000 units per day, in black the average of the regimens.

There is a distinct pharmaco-kinetic advantage in giving Calcifediol. It bypasses the liver activation process and when given by mouth it will its increase blood to above 30ng/ml (75nmol/L) within about 2 hours. We can see this in Figure 2.


Figure 2. Response to a single dose of Calcifediol


This means that in a patient admitted to hospital with Covid-19 pneumonia, Calcifediol must be given immediately and natural vitamin D is not an adequate substitute at this stage of emergency. 

However natural vitamin D must be given to the well before any illness, and certainly as soon as there is a positive Covid-19 test.



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

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