Covid-19 vaccination and miscarriage - ERROR

My recent Blog post was an analysis of an important study published in the New England Journal of Medicine.

The conclusion in this paper was obviously wrong giving false reassurance. It describes 104 miscarriages, but in calculating the risk of miscarriage the denominator used was 827, the number of women whose pregancies had been completed. 104/827 gave a very low risk.

The mistake in the paper was that of the 827 pregnant women whose pregnancy had been completed, 700 had been vaccinated only in the third trimester, after 27 weeks. They could not have had a miscarriage as the definition in the paper was that a miscarriage is before 20 weeks. The 700 had either full-term, premature, or still-births.

My mistake was to over-simplify in an attempt to obtain a true result from this paper. To do so I simply removed the 700 from the 827, finding the 127 who had been vaccinated early, 92 of them being peri-concepriion vaccinations. It appeared that only these 127 were at risk of miscarriage.

104/127 = 82% miscarriage risk. WRONG.

Vaccination and pregnancy - Correction

After a few more reads of the paper:

3958 pregnant subjects enrolled in the original studies.

The data analysis was during just 76 days, Dec 14 to Feb 28.

This meant that during this short window, only 827 had completed pregnancy, but all the others remained pregnant. It was only the 827 completed pregnancies that were the subject of this preliminary paper.

At this stage, there were:

104 miscarriages, 

96 before 13 weeks

These can be chosen as numerators for miscarriage risk as it is the miscarriage rate that is of interest at present, and which was reported wrongly in the paper.

Let us keep to 104 miscarriages as the numerator of the miscarrige risk: 104 pregnant women had a miscarriage – fact.

The paper used 827 as the denominator of 104/827. This is clearly the wrong way to calculate the miscarriage risk, as described above and in my initial analysis. 700 were not at risk of miscarriage because they had been vaccinated in the third trimester.

I simply subtracted 700 from the 827 denominator, giving a risk of 104/127. 

This was an oversimplification.

92 subjects received vaccination in the peri-conception days, between one month before last menstrual period and 14 days afterwards.

This is not a possible denominator if 104 is the numerator. We must add some early first trimester vaccinations, but how many? 

1132 subjects were vaccinated during the first trimester, up to 13 weeks. How many miscarried? We are not told.

Impossibility of a conclusion

It is not possible to be clear about the denominator as we do not know the outcome of the 92 peri-conception vaccinations.

Nor do we know the outcome of the 1132 first trimester vaccinations, most of the women still being pregnant at the end of the short window of the study. We do not know how many of the 1132 pregnancies resulted in miscarriages overall, but 12 of them did during the window of the study (104-92).

The denominator could be any number from 127 to 1224 (92+1132), the number at risk of miscarriage (all peri-conception + first trimester vaccinations).

The future of this study

Perhaps my 82% risk could be correct, but this is most unlikely. We simple do not have the data necessary to reach a robust conclusion.

The study was “Preliminary”. More detail and more comprehensive presentation of data might be available in a later paper.

The paper as published is not good. It appears that the main outcome measure is birth defects, hence it being an end of pregnancy study. The full-term and late births revealed no major problems.

It is not possible to reach a conclusion concerning the miscarriage rate, and it will require a longer follow up. 

As it stands the NEJM paper is rubbish. It should not have mentioned miscarriages without supportive information. I was trying to salvage a result more accurate than that in the conclusion, which was obviously wrongly based reassurance.

At present, on the basis of data presented, we can accept that Covid-19 vaccination appears to be safe in late pregnancy, but small sample size with no controls. However vaccination is best avoided in peri-conception days.

UK MHRA

A few days following my previous Blog, the UK Medicine and Healthcare products Regulatory Authority issued a report that stated that vaccination during pregnancy is safe.

It is not a research study but it is data based on a spontaneous and  informal self-reporting system of untoward effects after taking medicine or using healthcare products, the Yellow Card system. It was a brief report with just a conclusion, no numbers of miscarriages. It does not compare with the detailed prosepctive study in the NEJM, imperfect as this is.

The MHRA report tells us that vaccination during pregnancy is safe, but it does not identify the relatively small number of women who might have been vaccinated before they realised that they were pregnant, those who had missed a period by just two weeks. It is these women with peri-conception vaccination who are at risk of embryo damage or implanation failure, and consequently miscarriage. 

The report concluded that there was no excess of untoward obstertric events following vaccinations. As vaccinations have been in progress for only eight months, this "conclusion" must be regarded as premature.

Ref: UK MRHA

https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting

NEJM: further analysis

I have just received a paper that is severely critical of the NEJM paper. I wish that I had known about this earlier.

It will be available by email.

Urgent: Covid-19 vaccines and miscarriage risk

Corrected on August 26th 2021

This was the headline of news media in the UK on the evening of Saturday August 14th. It shows that Carrie Johnson, the wife of the Prime Minister, has been seriously misinformed, and that she is not an appropriate person to be advising the public on health issues. She is not a medical scientist.

Unfortunately, she does not realise that her recent miscarriage, sad as it was, almost certainly resulted from her first vaccination, but I do not have the precise time-line. Did she complete a Yellow Card to record the time-link between her first vaccination and the miscarriage? Do any women who have miscarried do this if the miscarriage occurs within three months of peri-conception vaccination?

Carrie Johnson is not the only person to be urging pregnant women to be vaccinated:

I have indicated in a previous Blog post that I have been concerned about deaths from Covid-19 of pregnant women in the UK, especially as most of them are of South Asian ethnicity. Vitamin D deficiency was almost certainly the major causative factor, and certainly the only factor that could have been corrected immediately. By government directive, vitamin D, like ivermectin and hydroxychloroquine has not been used in the UK for the sick and dying from Covid-19, a national disgrace.

Now there is the issue of whether or not pregnant women should be vaccinated against Covid-19. It is a contentious issue because we know that medicines given during pregnancy can have damaging effects. It is vital that new medicines are tested thoroughly before being given to pregnant women. Covid-19 vaccines are new medicines, and similar medicines have never been used in the past. 

Human testing of a new medicine must be with careful randomised controlled trials, and these must include signed informed consent. This is particularly important in the new vaccines because they are not yet licensed: they are used under Emergency Use Authorisation, which implies that they remain experimental.

Randomised controlled trials of vaccines given in pregnancy have not been undertaken, but many pregnant women in the USA in particular have received vaccines. Did the women give signed informed consent?

The rhetoric

"Language designed to have a persuasive or impressive effect, but which is often regarded as lacking in sincerity or meaningful content."

The debate continues in the UK, but debate and science are by-passed by media pressure for pregnant women to be vaccinated. Pregnant women are understandably hesitant, but rather than listening to their concerns and looking at the science, pressure is put upon them to change their minds. 

The pressure is even coming from "England's Top Midwife": 

Jacqueline Dunkley-Bent, Chief Midwifery Officer for England, said: “Vaccines save lives, and this is another stark reminder that the Covid-19 jab can keep you, your baby and your loved ones, safe and out of hospital".5 Aug 2021

Powerful rhetoric, but wrong. 

Headline in the Guardian, July 30th 2021

Jacqueline Dunkley-Bent and Linda Geddes are seriously misinformed.

The data

The data presented appear to be dramatic, in fact too dramatic:

171 pregnant women admitted to hospital in the UK on account of Covid-19.

168 had not been vaccinated (98%).

3 had been vaccinated (2%). 

Such a huge difference is very surprising. Is vaccine hesitancy in pregnant women really so strong, 98%? If so, notice should be taken of this rather than just persuading them to change their minds. 

This is of course observational data, not a randomised controlled trial. But as we have seen in respect of vitamin D studies (and cigarette smoking in the 1950s), observational data are of immense importance. In human investigation, we usually need to rely on observational data.

The data have two, perhaps three theoretical explanations:

1. Vaccination is spectacularly successful in preventing Covid-19 in pregnancy (hence only 3 vaccinated pregnant women with Covid-19 in this study of 171).

2. Vaccination is spectacularly successful in preventing successful pregnancy (hence only 3 vaccinated pregnant women in this study of 171).

3. A combination of 1 and 2.

We need more information, and it is readily available from observation of pregnant women vaccinated against Covid-19 in the USA. 

The study in the New England Journal of Medicine.

https://www.nejm.org/doi/full/10.1056/nejmoa2104983

In this study the manufacturers of the vaccines were either Pfizer-BioNTech or Moderna.

From a database of 3958 participants in the "V-Safe Pregnancy Registry", the study identified 827 women, aged 16 to 54 years, who had been vaccinated between December 14th 2020 and February 28th 2021 and who had completed pregnancy. Slightly more than 60% were in the age range 25 to 34.

The overall pregnancy loss was 115 (14%), 104 miscarriages, 1 stillbirth, 10 induced abortion or ectopic pregnancy.

127 were vaccinated in early pregnancy, 92 of them during peri-conception, that is, shortly before pregnancy or during early pregnancy, up to 30 days before the last menstrual period (LMP) or up to 14 days after the LMP.

We are not given a breakdown of data on the 92 and the remainder of the 127, so they must be analysed together.

700 received vaccine in third trimester of pregnancy, this being after 27 weeks (27/40)

104 of the pregnant women had a miscarriage, spontaneous abortion (SA) in medical terminology.

104 miscarriages out of 827 pregnancies = 104/827, which expressed as a percentage = 12.6%.

This formed the conclusion of the paper, reassuring women all over the world that this is an acceptable miscarriage rate, not dissimilar from "normal experience".

BUT THERE IS SOMETHING SERIOUSLY WRONG WITH THIS CALCULATION

 STATISTICAL SPIN

This section has been corrected

We can be clear about the numerator, 104 miscarriages. This is what we are investigating.

2/4=50%. If we want to reduce this percentage, we need to make the denominator bigger.

2/40=5%

What has happened in this paper is that the denominator has been made bigger, from 127 to 827.

A few simple facts are necessary to help understanding about pregnancy, perhaps those conducting the study were ignorant of thes facts..

By definition, a miscarriage (SA), the end of an unviable pregnancy, must occur before about the half-way point of a normal pregnancy. In practice 23 weeks is usually chosen for definition as before 23 weeks a delivered foetus will not be viable. A miscarriage is before 23 weeks (23/40). In the study miscarriage was defined as end of pregancy before 20 weeks, but this will not make a difference to the analysis.

If a pregnancy comes to an end after 23 weeks but before full term normal birth (40/40) it is called a premature birth, or a stillbirth if the foetus has died in utero.

The first trimester, up to 13 weeks, is the embryonic stage, and understanding this is of vital importance. The embryo develops from a single fertilsed cell which divides and differentiates into its human form. It is during this differentiation and formation that the embryo is highly vulnerable to damage with consequent abnormalities. Examples are medical teratogenicity due to thalidomide or anti-epileptics, also viral damage due to rubella. Severe damage can result in miscarriage. 

When the embryo has reached its human form, at just before 13 weeks, it becomes a foetus. The process for the remaining two-thirds of gestation is for growth and maturation rather than differentiation. Brain maturation is particularly important in the third trimester.

The NEJM paper tells us that 700 of the 827 were vaccinated only in the third trimester, 27 to 40/40. By definition this is much too late for a miscarriage. These 700 pregnant women could not have had a miscarriage, and so they cannot be included in the denominator of the calculation of miscarriage risk. 

The reality is this:

127 pregnant women received very early or peri-conception vaccination, before or very early in pregnancy.

104 of them had a miscarriage, the great majority we are told being in the first 13 weeks, the embryonic stage. Miscarriage is embryo loss.

But the 127 were only a subgroup of 1132 pregnant women who received the vaccination during the first trimester with the great majority remaining pregnancy at the time of the study. 

104 miscarriages out of how many? We do not know. It might have been 127 (= 82% miscarriage rate), but it might have been 92+1132 = 1224.

Read more of this in the next Blog post.

WHY DID THIS DISTORTION OF STATISTICS HAPPEN ?

This true miscarriage rate has been hidden from the world by a paper that is so badly written that the large number of words disguises the important numbers. The conclusion is either seriously at fault or is fraudulent. How it passed peer review to be be published in the prestigious NEJM is a mystery. 

It seems to me that there was a failure to understand the difference between an embryo and a foetus, and the huge difference between exposure of an embryo and exposure of a foetus to a potential poison, whether biological or chemical. It is important to note that the miscarriages occurred during the embryonic phase. Pregnancy is divided into three trimesters for a good reason, as the stages are distinct and should not be combined into one in scientific analysis.

We have much to learn from the thalidomide tragedy of the late 1950s. If the pregnant women took thalidomide (to help with sickness) in the embryonic stage, the baby was in danger of being born with brain mal-development, eyes incompletely formed, or serious limb shortening. If however thalidomide was taken after day 42 following conception there was no damage to what by then would be be the foetus. 

And so it is with vaccinations. There is serious damage or implantation failure in the embryonic stage, the first trimester, but no damage in the third trimester, during which pregnant women could perhaps be vaccinated safely. Although thalidomide appeared to be safe in the third trimester, medicines regulatory agencies banned it completely.  

Few people will take the trouble to access and look at the paper, and those who do will probably read just the abstract and perhaps the conclusion. These can be effectively fiction, the conclusion that is politically convenient.

What do we do now?

As a clinical doctor I have always been cautious, well-aware of the dictum "Primum non nocere" (first do no harm), part of the Hippocratic oath. I am only too aware that it is much easier to do medical harm to people than to do good, and so restraint and caution are very important. "Evidence-based medicine" has become a dictum in recent years, but during this pandemic control of medicine has shifted from professional to government authorities, which have shown restraint only in treatments other than vaccines, and then total restraint without science. 

Vaccinations are being given on Emergency Use Authorisation and use should be scientific, based on a prospective research protocol so that we can learn. But this is not happening. The study described above was retrospective and opportunistic. It provided very useful data, and it is the best that we have. It is probably too late for prospective structured research into the effect of vaccination on the outcome of early pregnancy. 

To continue to vaccinate women in late pregnancy is reasonable, as it would have been reasonable to continue prescribe thatlidomide to women late in pregnancy. We have seen clearly that the miscarriages occured early and perhaps mainly before the pregnancies would have been officially recorded. Research into the outcome of pregnancy must therefore be based on a data-set of vaccination of all women of child-bearing age, including those not yet pregnant, as was the study published in the NEJM. 

However this will no longer be possible prospectively  as informed consent for vaccination of such women must include information that very early and peri-conception vaccination will give risk of miscarriage at present unknown, but not the risk given in the NEJM paper. Would a woman accept this risk?

Covid-19 & VItamin D – something strange is happening in 2021

Mid-summer sunset across the Ribble Valley

2020 was memorable for the Covid-19 pandemic, but the behaviour of the pandemic conformed to the pattern that we expect in the natural world. 

The pandemic became significant in the UK during the month of March 2020, and on March 23rd lockdown was introduced as we had experienced 258 deaths. Despite this, cases and deaths continued to increase until mid-April 2020, when we experienced a maximum of 919 deaths in one day.

Mid-April is the time in the UK when the mid-day sun becomes more than 45 degrees above the horizon, and so vitamin D production starts. As a result, immunity becomes more effective and so there was a steady decline in Covid-19 deaths to a minimum level in August, with fewer than ten deaths per day. This is the same pattern for all respiratory infections, the non-specific beneficial effects of the summer enhancement of immunity. It is not difficult to understand.

As predicted by the natural annual cycle of respiratory infections, the incidence and deaths from Covid-19 increased in the early winter, when vitamin D production ceased and vitamin D reserves were reducing. A steady state was observed during November and December. This was seen in all European countries and in North America.

Figure 1. Covid-19 deaths in the UK during 2020

Figure 2. Covid-19 deaths in the Netherlands during 2020

Figure 3. Covid-19 deaths in Canada during 2020

However a sudden and unexpected increase in Covid-19 cases and deaths occurred in January 2021. What was even less expected and which remains unexplained is the sudden decrease in cases and deaths that followed in February. There was no obvious natural or therapeutic enhancement of immunity that could account for it. There was of course the introduction of the vaccination programme in mid-late December, but if it is viewed as causing the decline in deaths (much too rapid) it could equally be viewed as somehow causing the increase. 

Figure 4. Covid-19 deaths in the UK during 2020 and 2021

I have described previously the winter increase in Covid-19 deaths in the Andalucía region of Spain. A public health initiative in late November 2020 was to use Vitamin D in its activated form calcifediol, 25(OH)D, to protect the vulnerable elderly. It appeared to have a dramatic effect as there was a sudden drop in the number of deaths during December, with no obvious alternative explanation.

However this dramatic benefit was reversed by an equally dramatic increase in deaths in January. As in the UK it was was brief peak, but the experience in Andalucía indicated that this peak appeared to be vitamin D / immunity resistant. Most strange, and still unexplained.

Figure 5. Covid-19 deaths in Andalucía, Spain, during 2020-21

The end of the winter saw the expected decrease in cases and deaths as the vitamin D season started again, and in 2021 this was supplemented by the immunity benefits of the vaccination roll-out programme. 

All was going well in the early summer of 2021 in Europe, and then something else happened that was completely unexpected. In the UK, in June and continuing into July, there was a sudden peak of Covid-19 cases, five times greater than the April 2020 peak.

Figure 6. Covid-19 cases in the UK during 2020-21

The strange thing about this peak is not just its size, but that it occurred during the summer months when we would not expect a sudden outbreak of a respiratory virus. The number of cases is far greater than in the early stages of the pandemic in 2020. 

There are many more Covid-19 "tests" being performed in 2021 than in 2020 and there are concerns about a large number of "false positives", but this would not explain the huge difference between May and July 2021. There is something happening that is real rather than a change in testing methodology.

This 2021 peak has perhaps been defying not just expectations but also the natural cycle as we have known it and which we experienced in 2020. The implication of this peak is that it is resistant to natural immunity (and also to the vaccination programme).

The high transmissibility of the "Delta Variant" would not automatically translate into clinical illness in mid-summer. It has been suggested that this peak in the UK was the result of crowds congregating for soccer matches in Euro-2021 during June, but this is far from robust an explanation.

The point is that the June – July peak is not just a UK phenomenon. It has been more dramatic in the Netherlands, with a much more sudden onset and a little later in July.

Figure 7. Covid-19 cases in the Netherlands during the summer of 2021

But on the other hand it is not particularly dangerous. Although the number of cases has risen dramatically, the number of deaths from Covid-19 has remained low in the Netherlands and in the UK (with a slight upturn in August).

Figure 8. Covid-19 deaths in the UK during 2020 (blue) and 2021 (green)

The natural fall in deaths in the late Spring and Summer of 2020 is clear, and the low number of deaths in 2021 is very reassuring, a result of natural immunity and vaccine immunity. 

It is a mystery why the number of cases behaved so very differently from deaths, and why cases increased so dramatically. No doubt the reason will emerge.

But I have just come across the steepest increase in cases per day, which has taken place in Iceland during late July. Why has vitamin D immunity not suppressed it? What can possibly be causing it, again in the middle of the summer? 

Figure 9. Iceland : Covid-19 cases per day 2020 and 2021
(Source: Our World in Data)

Covid-19 and Vitamin D : Barcelona revisited and again ignored

July 2021. The UK is enjoying an excellent summer, hot and sunny, no climatic catastrophies

Covid-19 and Vitamin D

On September 3rd 2020 the UK had experienced 43,693 Covid-19 deaths, one of the highest deaths per million in the world. The hospitals had been quiet during the summer, the season of vitamin D production and high immunity, but as winter was approaching Covid-19 cases and deaths were about to increase. 

UK: Covid-19 deaths per day during 2020

On this day we received a report from Córdoba, Spain, that vitamin D in its part-activated form 25(OH)D, calcifediol, had been remarkably successful in patients admitted to hospital on account of Covid-19 pneumonia. This is just what we needed and it caused great excitement in those who had read the report and who were anxious to reduce deaths.

It is necessary to understand a little of the metabolism of vitamin D. The oil 7-dehydro-cholesterol (7-DHC) is synthesised in the skin, and when the UV energy from the Sun is strong enough in the summer months it converts 7-DHC into vitamin D by splitting a specific inter-atomic bond. It is also important to appreciate that the thin dry skin of the elderly produces inadequate amounts of 7-DHC and so vitamin D deficiency is inevitable in this age-group. 

Vitamin D produced in the skin is transported in the blood to the liver. A slow process then takes place in which an -OH group is added to the molecule to form 25(OH)D, also known as calcifediol. It is the same after vitamin D is taken by mouth, the process of activation taking up to two weeks. 

It takes two weeks for blood level of 25(OH)D to increase above 30ng/ml following different oral vitamin D regimens.

This presents no problem in the steady state of normal life. However it presents a serious problem to someone who meets a sudden serious illness, and to many people at the time of a pandemic that is due to a new virus to which we have no historic immunity. Under such a circumstance immunity must be optimised immediately but this is not possible for someone who is vitamin D deficient. The escalation of immunity is likely to fail, the consequence being worsening illness, cytokine storm, widespread damage, the need for ventilatory care, and a high risk of death. This was the situation facing the 43,693 Covid-19 patients who died in the UK before September 3rd 2020, and many others who survived serious illness. 

Brazil

As the escalation of immunity is of the greatest urgency, vitamin D itself cannot be expected to help. It will take much too long to become adequately activated. If someone has bacterial pneumonia it is of little value accepting a two week delay before giving the life-saving antibiotic. The vital disadvantage of delay was demonstrated in Brazil. In a controlled trial vitamin D was given to 102 patients with Covid-19 on an intensive care unit, and a 120 acted as controls. The main endpoint was the time to discharge from hospital, and there was no difference between the two groups. 

This trial was widely reported as indicating that "vitamin D is of no value". This was ideal news for those who wanted vitamin D to be buried. But the paper made no mention of the metabolism and activation of vitamin D. It also made no mention of the clinical trial in Córdoba, and no acknowledgment of the obvious metabolic advantage of calcifediol.

Córdoba

The Córdoba trial showed a very positive benefit from calcifediol, which had been used in an imaginative way, knowing that at the stage of serious Covid-19 pneumonia "raw" vitamin would act too slowly to be of benefit. 

Instead of two weeks, calcifediol given by mouth reaches an adequate blood level after about two hours. The difference between "raw" vitamin D (cholecalciferol) and 25(OH)D (calcifediol) is obvious in terms of dynamics and effectiveness. The great potential superiority of calcifediol is easily understood.

25(OH)D, calcifediol, achieves blood level greater than 30ng/ml after just two hours

Of the 76 patients admitted to hospital on account of Covid-19 pneumonia, 26 were controls, being given standard high quality care. 13 (50%) required transfer to ICU and 2 died. 50 patients were given Calcifediol in addition. 1 (2%) required transfer to ICU and there were no deaths. 

This huge benefit from calcifediol was clear, but once again vitamin D had to be buried from human view, for reasons explained in a previous Blog post: if vitamin D/25(OH)D were to be effective, then vaccines could not be given Emergency Use Authorisation. It was the UK National Institute for Health and Care Excellence (NICE) that performed this service to maintain the "official" narrative, informing clinical doctors struggling to prevent deaths that the dramatic result of the Córdoba study must not influence clinical practice. And so it happened: calcifediol was not used. There was no debate. There was no "peer review". NICE could not be challenged. Clinical doctors had lost their ability to assess risks and do their best for their patients. 

The use of calcifediol has no disadvantage, only benefit, but this was not of "official" importance. The number of deaths continued to increase. The denial of calcifediol could be regarded as a crime against humanity. The patients who were to die from Covid-19 would not be given the choice of calcifediol treatment, but they will be just be pawns in a much bigger game.

Barcelona, February

Five months and 50,000 UK deaths later we received the first results of another controlled clinical trial from Spain, this time from Barcelona. A larger trial involving 838 patients admitted to hospital with Covid-19 pneumonia. 447 were treated with Calcifediol and 391 acted as controls receiving just standard high quality care. 

Of those who received calcifediol, 20 (4.5%) required transfer to ICU, compared to 82 (21%) of the control group. On the basis of intention to treat, 21 (4.7%) of the calcifediol group died, compared to 62 (15.9%) controls. In practice, some of the control patients were given calcifediol following transfer to ICU. The clinical staff wanted to avoid preventable deaths, and quite rightly.

This highly significant result must be enough. The pressure on ICUs was so great that such a reduction in demand would have been very welcome, had it been allowed. Once again there was no debate within UK medicine, just a denial of benefit by Professors Naveed Sattar and  Adrain Martineau on behalf of NICE. The structure of the trial was criticised for not being "perfect", a sad example of the good being over-ruled by the illusory perfect. 

In practice perfection is impossible to achieve. I have illustrated previously that in both Cordoba and Barcelona, the two trial groups were very closely matched to the point that any imperfection would be over-ruled by the very large benefit of treatment. 

Activated vitamin D, 25(OH)D, calcifediol remained unavailable for use in the UK and elsewhere. Patients continued to die unnecessarily.

Vaccines

The new experimental gene therapies, now known as vaccines, came into clinical use under FDA Emergency Use Authorisation (EUA) in December 2020. By this time 75,136 Covid-19 deaths had occurred in the UK. But we could hardly expect an instant effect from the vaccines. 

In fact following the introduction of vaccinations there was an unexplained surge of cases and deaths in January 2021, reaching a maximum of 68,053 cases on January 8th and 11,062 deaths on January 7th. The surge settled and by March there were fewer than 10,000 cases and fewer than 200 deaths per day. 

UK: Covid-19 deaths per day since the arrival of the pandemic

The organisation of the vaccines was a particular triumph in the UK but the benefit was of prevention. People admitted to hospital with severe Covid-19 pneumonia would not benefit from vaccination and would continue to have a high mortality rate despite high quality intensive care.  

In the six months following the introduction of vaccines in December 2020 there were 60,616 Covid-19 deaths in the UK. It is inexcusable that vitamin D as calcifediol was not given to those who were critically ill despite the vaccination initiative, in an attempt to reduce these deaths. 

It was in the first week in February 2021 that the results of the Barcelona trial became available. 

Barcelona, June 

The Barcelona pre-print was rejected by Professors Naveed and  Adrian Martineau on behalf of NICE as soon as it appeared. Their comments were published on February 15th. There was no debate, no peer review, just the opinions of two people. The misuse of great power. They suggested that the process of randomisation was irregular and that this would invalidate the result. I have pointed out that randomisation was very successful but not quite perfect. They also complained that the paper had not been peer-reviewed. More evidence was demanded while people continued to die.

The pandemic was evolving rapidly. Urgency was essential, as was happening with vaccine development and subsequent Emergency Use Authorisation. The results of many studies of a variety of treatments were released before publication so that clinical action could be taken should the clinical staff think it appropriate. Delays in treatment should be minimal. 

The initial communication from Barcelona appeared in early February 2021. On June 7th the paper was released on-line before being printed in the Journal of Clinical Endocrinology and Metabolism. It had been peer reviewed and accepted for publication but this process took four months, during which time many deaths had occurred. 

Once again vitamin D as calcifediol, a natural product, was shown to be very effective and without untoward effects. Perfectly safe, very cheap, very effective. Patients treated with calcifediol had an 87% reduction in need for ICU compared to controls.

Action ?

It might have been expected that we would have seen headlines in the medical journals and national press, but none appeared. At least in the UK, and apparently in other European countries and North America, the paper was dead at birth. NICE has made no comment, but news of the paper has circulated on the internet. Perhaps clinical doctors can now act and use calcifediol for the critically ill on the basis of what they have read, before NICE says "No". But professionalism has been replaced by government control. Covid-19 has become Covid-1984.

Vitamin D is powerful but only in a dose adequate to optimise the escalation of defensive immunity. Unfortunately we are up against another government institution rather than a medical professional body, the Royal Colleges of Physicians which have been responsible for medical knowledge and excellence for 500 years. 

The Standing Advisory Committee for Nutrition (SACN) advises the government about vitamin D. It appears to have little awareness of the role of vitamin D and its metabolites in the escalation of defensive immunity and the suppression of the cytokine storm, mentioning just "a suggestion". SACN acknowledged only the role of vitamin D in bone maturation, recommending a low orals dose of just 10mcg, 400units each day, about a tenth of what is required for optimisation of defensive immunity.

Controversy of the correct requirement of vitamin D has caused confusion and led to problems with implementation and interpretation. When "vitamin D treatment" is mentioned, what dose or achievement is being described? Of course the achievement should be that of a given blood level. In respect of bone and calcium health a blood level of 10–20ng/ml (25–50nmol/L is adequate. Experience during the Covid-19 pandemic indicates that a target range of 40–ng/ml, 100–150nmol/L is safe and effective, but variation of thought remains. The official denial of the benefit of vitamin D during the pandemic has stifled the opportunity for definitive research.

July 2021

We are now seeing an unexpected rapid increase of "cases" of Covid-19 in the UK, also in the Netherlands and Spain. The increase is also starting to show in other European countries and in the USA. This is not matched by an increase in deaths, but there is an increase in hospital admissions in England, from 100 to 500 per day.

These patients admitted to hospital could be given vitamin D as calcifediol to diminish the need for transfer to the ICUs and to reduce the numbers of deaths. But it not happening. Clinical doctors are still being denied the opportunity to use calcifediol and patients will continue to die when they need not do so.

Why are cases increasing in 2021 at the time when they were diminishing in 2020?

Covid-19 and Vitamin D : Politics and the influence of the US FDA

Covid-19 and Vitamin D : the influence of the FDA

In March 2020, the pandemic of Covid-19 was causing chaos in the hospitals of Europe and elsewhere, a major logistic challenge being the large number of critically ill patients with Covid-19 pneumonia (lung disease) requiring ventilatory care. The approach of the UK and other governments was to commission and buy more ventilators and even emergency hospitals (Nightingale hospitals in the UK). This gross oversimplification of the action required was easily made by politicians who regarded hospitals as automated factories, unaware of the need for large numbers of skilled doctors and nurses to provide the intensive and ventilatory care that would be required. 

Some medical practitioners and scientists had a knowledge of the importance of defensive immunity in minimising the effects of a new virus to which we had no historic immunity. The details had been worked out during the previous 40 years, and were available for all to read. It was clear that vitamin D has a pivotal role in escalating the cascade of defensive immunity.

Previous evidence was available that deficiency of vitamin D is very common, in the UK, in Europe generally, and indeed world-wide. It was also clear that vitamin D deficiency is particularly common and serious in the elderly (whose dry skin is unable to produce vitamin D), in people of black and Asian ethnicity living in the UK and other north European countries, and in the obese.

Why was this knowledge not applied when the pandemic started? Surely the best brains of the nation were at work, and they would have known that the best immediate defence would have been to optimise as soon as possible the defensive immunity of the population, especially those at particular risk – the elderly who were to die from Covid-19 in large numbers. Why was the opportunity to minimise these deaths completely missed?

WHO and failure of duty

It must have been the duty of Public Health England and other national public health bodies worldwide to take immediate action to correct widespread vitamin D deficiency, but it must also have been the duty and responsibility of the World Health Organisation. It was not to be. The WHO even redefined "immunity" so as to exclude natural (vitamin D associated) immunity and acknowledge only man-made immunity, that is vaccines. It later decided to recognise both. But it was clear that the objective of the WHO would be to support the development of "vaccines" to the exclusion of all other medications. Why was this? Why was vitamin D deficiency and its correction to be ignored?

It should be noted that the approach of the much-applauded new experimental gene therapies is to develop immunity against a specific virus, but strictly speaking they are not vaccines. However, the term "vaccine" is more acceptable to the population than "gene therapy", and so this description is used.

Many clinical doctors would be aware of the importance and extent of vitamin D deficiency, and the automatic clinical duty of a doctor to correct it. How could the WHO control and suppress the prescribing of vitamin D by these clinical doctors? 

WHO policy

The key to understanding what happened concerning the denial of vitamin D lies in the WHO policy of "vaccines for the world population". The problem was that vaccines take several years to develop and then to test for both effectiveness and safety. 

The vaccines would not become available until the end of 2020 at the earliest. However even though short-term evidence of benefit might be available by that time, full demonstration of safety would take much longer and so licensing for use could not be anticipated. It was therefore necessary for the vaccines (each one) to be issued with Emergency Use Authorisation (EUA) by the US Food and Drug Administration (FDA). This was achieved with clinical trial evidence of reduction of incidence of Covid-19 following vaccination. Several vaccines received authorisation in this way during the following six months.

The US EUAs were followed by emergency use authorisations being issued by UK, EU, and other national agencies. An extremely well-organised roll-out of vaccinations followed, the objective being world population vaccination by the end of 2021, on the basis of EUAs and without licences.

The granting of an EUA acknowledges that the medicine / vaccine concerned is still experimental. The EUA is granted on the basis of the clinical experiments, the controlled clinical trials, being continued so as to demonstrate the incidence and range of untoward events in the two groups, the vaccinated and the controls. Only in this way could the safety of the vaccines be demonstrated, by comparing those who had received the vaccines and those who had not.  

Unfortunately this has not happened and will not happen because at the end of the initial clinical phase, the unvaccinated controls were "unblinded", and the great majority appear to have been vaccinated at this stage. The controls ceased to be and so the long-term safety evaluation will be uncertain. A clear and detailed account of this process written by Peter Doshi, senior editor of the British Medical Journal, was published on-line on May 18th 2021. 

FDA rules and Vitamin D

To understand the implication of the EUAs and their effect on the use of vitamin D, it is necessary to read the small print of the FDA rules for the granting of an EUA. The rules state that:

"For FDA to issue an EUA, there must be no adequate, approved, and available alternative to the candidate product for diagnosing, preventing, or treating the disease or condition." 

As the decision had been made from the onset that vaccines were to be developed (at great cost), and ultimately by more than 50 companies in the world, it was essential that there must be no obstruction to the EUAs. Was there in reality an available alternative to the vaccines for prevention or treatment of Covid-19? 

In March 2020 there could not possibly have been any evaluation of specific medications in the treatment and prevention of Covid-19. There were a number of possibilities, based on the experience of other infections, bacterial and viral, and basic science. It was clear from basic principles that the first level of defence against a virus infection, especially a novel virus, is the innate immunity of the body. There was much understanding of the processes involved, and the pivotal role of vitamin D in its active forms in the escalation of defensive immunity. It was also known that deficiency of vitamin D was very common, especially in the groups that would be very badly affected as the pandemic unfolded. It had also been demonstrated before the appearance of Covid-19 that vitamin D supplement would reduce the incidence of respiratory infection.

So here lay a problem. How could EUAs for vaccines be granted with vitamin D being readily available? It had to be buried out of view of the public and their officials. In particular successful clinical trials of calcifediol, 25(OH)D (activated vitamin D) had to be "censored". 

The suppression of knowledge of vitamin D has been a great achievement and triumph of officialdom. Vitamin D deficiency has been ignored, irresponsibly so in the elderly, in the obese, and in people of black or Asian ethnicity. The denial of this scientific knowledge can be regarded as a crime against humanity. There were more than 75,000 Covid-19 deaths in the UK during 2020, and those who died were not given the opportunity or the choice to receive vitamin D. There was no public health policy to test for vitamin D deficiency, knowing of the high prevalence and importance of such deficiency at this time. In practice the testing of blood levels of vitamin D was discouraged.

The achievement of the introduction of vaccines with just Emergency Use Approval was at the cost of many deaths, especially of the known at risk groups, that might have been prevented by the  correction of vitamin D deficiency. 

The importance of vitamin D deficiency has been shown in a study from Israel. 

There was a 3% death rate in those admitted to hospital who were not vitamin D deficient. However those who were severely vitamin D deficient (<10ng/ml, <25nmol/L) had a 14 times greater risk of critical disease and 25% died.

During the pandemic we have seen many careful observational studies of the great disadvantage of vitamin D deficiency, which could have been corrected rapidly, cheaply, and safely. This was not done so as not to jeopardise the issue of EUAs to the vaccines.  

Vitamin D deficiency was not even considered, and official pronouncements referred (always negatively) to "vitamin D supplements", never referred to the correction of vitamin D deficiency, and always denied the role of vitamin D in the escalation of defensive immunity.

The "sensible" approach at the onset of the pandemic would have been to correct vitamin D deficiency immediately, with priority to the elderly and the black and Asian ethnic groups. This would have protected the population during the course of 2020 until the vaccines became available, but FDA rules meant that this sensible and responsible policy was not to be.

The rule meant that exclusion and silence were also applied to Ivermectin and Hydroxychloroquine, both of which had been shown to be effective against Covid-19.

After FDA Emergency Use Authorisations

In mid-2021 vaccines are still being given on the basis of EUAs. No vaccine has yet received a licence for use. The EUAs mean that if there are any untoward effects, responsibility and compensation will be the function of governments who issued the EUAs, and not the pharmaceutical companies themselves. This can be of only good news to the companies.

How long can an EUA continue before a licence becomes necessary? It is far from clear and at this stage the FDA is unlikely to call a halt to mass vaccination while awaiting licensing. However once licences are granted vitamin D can emerge from seclusion and come into clinical use and correct the widespread deficiency that has been highlighted during the pandemic.

But there is another problem. Licensing will require full evaluation based on continuation of the randomised controlled trials, on the basis of which EUAs were based. But of course it took just a short time, about two months, to demonstrate a reduced risk of Covid-19 in those receiving a vaccine compared to controls. It would take much longer to demonstrate safety. 

Adverse event have occurred in some people who have received vaccines, events such as pulmonary emboli or even death. They have generally been dismissed as "coincidences", that they would have happened if the vaccines had not been given. The usual approach would be to compare the event frequency in the vaccinated group with the event frequency in the control group. Simple, but not possible now. At the end of the first stage of the controlled trial, the randomisation code was broken, and the control subjects were given the opportunity to be vaccinated. The vast majority took the opportunity. 

This means that there is no longer a control group. Randomised controlled evidence cannot be presented to the FDA and similar licensing authorities. Safety considerations will be seriously curtailed. Can EUAs be continued indefinitely? This might be acceptable to companies from whom financial responsibility has been taken by governments.

The pharmaceutical companies that gave vaccines to the control subjects state that they did so for ethical reasons, and these are understandable as there are ethical constraints on controlled trials. Controls can become sacrificial victims to "the truth", as I have pointed out in a previous post. 

It is understandable that with-holding vaccines from controls once benefit had been demonstrated was considered to be ethically unsound, but it puts the FDA in a difficult position concerning licensing. However the same ethical approach to vitamin D / calcifediol trials was used to dismiss these trials from public view and practical application.

The vaccine developments have been remarkable, but the dismissal of vitamin D and the correction of its deficiency has been a disgrace.

A failure of WHO

I mentioned that the WHO needed to prevent doctors from prescribing vitamin D, but this is not actually correct. It would have been accepted and indeed ideal if doctors were to prescribe and encourage vitamin D, as long as it was beneath the FDA radar, as long as it was done on the quiet so that EUAs could continue.

Although there has been continuing official denial of the benefits of vitamin D, there has been a strong "grass-roots" movement. Sales of vitamin D in pharmacies and health food shops have escalated during the pandemic, including the ideal doses of 2,000 to 5,000 units daily. Many clinical doctors have told me that "We are all taking vitamin D", and recommending it to their patients. This includes hospital doctors. This is good news and it will have contributed to the very low number of deaths from Covid-19 during the Spring and early summer of 2021, the onset of the Vitamin D Production season.

With vitamin D being given in good dose unofficially, any benefit from vitamin D would not be measured and the totality of benefit would be attributed to "official" actions: lockdown and vaccines. The leaders of the nation and their medical advisors would welcome the increase in the number of people taking vitamin D, even though they would deny knowledge of it.

June 2021

The overall great improvement in the immunity of the UK and other populations is shown in the figures below, a comparison between 2020 and 2021. The number of deaths per day is now very low. In the UK an average of about 1,600 people die each day, and so five Covid-19 deaths should not cause great alarm.

The numbers of hospital and ICU admissions are also very low, again a great benefit of improved immunity. The number of cases has risen in recent weeks, probably the result of more freedom of the people. This time in 2020 we were in serious lockdown with very little road traffic. The increasing traffic density now is a measure of freedom of travel and relaxation of mixing rules. "Cases" are not easily defined, but as there has been a policy of more Covid-19 tests for all, no doubt most of the cases will be asymptomatic positive tests.

UK: daily deaths from Covid-19, 2020 and 2021

UK: daily cases of Covid-19, 2020 and 2021

The increase in the number of cases now is much less than in January 2021, a peak that has not been satisfactory explained.

UK: daily cases of Covid-19, November 2020 to June 2021