Answering Your Questions about the COVID-19 Vaccines

The United Kingdom has approved the BioNTech/Pfizer vaccine and the very first people in the world have received their first jabs against COVID-19. The end should be in sight of this pandemic. Following previous posts, I’ve been asked a lot in person and online about the COVID-19 vaccines and vaccination in general. Here I’ve tried my best to answer them. Hope you find them useful. Please note although I am a doctor I am not involved in any of the trials mentioned.

How does the immune system work?

The human immune system is divided into two parts: the innate and adaptive. We’re born with the innate immune system whilst the adaptive is something we develop. The innate immune system is broad while the adaptive is specialised. The innate immune system consists of cells (phagocytes) which ‘swallow’ and destroy bacteria, viruses and other disease-causing organisms (pathogens). This happens quickly after being infected. These cells break up the pathogens into smaller parts which they then display on their surface. Cells called helper T cells ‘read’ these smaller parts and start the adaptive immune response. Cells called B lymphocytes are activated and turn into plasma cells which start producing antibodies. These are proteins designed to specifically counteract one particular pathogen. They fit around proteins called antigens on the surface of the pathogen. After doing this they stop the pathogen functioning, in the case of viruses this can stop them being able to invade cells, and helps the phagocytes find and swallow them. The helper T cells also activate killer T cells which find and destroy cells which have been infected by the pathogen. The adaptive immune system as a result is slower. But it lasts. Both B and T cells retain ‘memory’ of that pathogen so if we are infected again they can start working immediately to destroy it. It’s this memory which is the basis of vaccination.

How does a vaccine work and how long do they take to produce?

Even in the early days of what we would recognise as Medicine people noticed that patients who survived some infections, such as smallpox, would never suffer the disease again. The concept of inoculation was based on this. Dried smallpox pustules were scratched into the skin or blown up the nose of patients. The majority of people would develop mild symptoms but then be immune to smallpox. Some patients would develop full-blown smallpox and so a safer alternative was sought. The story of Edward Jenner, the English country physician, is famous. He noticed how dairymaids who contracted cowpox, a mild disease, never suffered from smallpox. He scratched cowpox pustules into the arms of a boy called James Phipps who then developed a fever. Once Phipps recovered Jenner repeatedly injected the boy with smallpox pus. The boy showed no symptoms. The process was called vaccination from the Latin word for cow.

Vaccines usually consist of a weakened, non-infectious version of a pathogen or a part of a pathogen. The idea is to activate our adaptive response (which is why following a vaccine we often feel unwell) and so give us that ‘memory’ ready to fight the pathogen in the future.

But this takes time. Vaccines traditionally take about 10-years to produce.

You can hear me talking to my Pharmacist colleague Kunal Gohil about the immune system and the process of vaccine production here:

COVID-19 Part Four: The search for a cure — Take Aurally
A feature of the COVID-19 pandemic has been the rush to find the magic bullet to defeat it. Under the heading of…www.takeaurally.com

So how did we make the COVID-19 vaccines so quickly?

The Pfizer, Moderna and Oxford vaccines have all been made using new methods.

The Pfizer and Moderna vaccines use messenger RNA. Human beings (like most life on Earth) store our genetic material as DNA. DNA is like a blueprint for making proteins. The blueprint is ‘read’ and something called messenger RNA (mRNA) is made. The mRNA is used by our cells as a code to make the proteins which we use to live.

The Pfizer and Moderna vaccines use mRNA that codes for the spike protein on the COVID-19 virus wrapped in small fatty molecules to stop the mRNA from being destroyed by our enzymes. The mRNA is read by our cells who then make the protein to be detected by helper T cells.

The Oxford vaccine uses a harmless virus which causes the common cold in chimpanzees called an adenovirus. The adenovirus was altered to express the COVID-19 spike protein. The end result is the same: our helper T cells detect the spike protein and kick off our adaptive immune response.

Although these vaccines have been produced in response to a disease we’ve only known about for a year, the technology behind them has been decades in the making. New ways of making vaccines, called platform technology, have been sought for over twenty years as a way of being able to provide new vaccines quickly to fight a new disease. While the vaccines feel like they’ve been produced overnight they’re actually the result of lots of preparation. In January 2020 the SARS-CoV-2 virus was first identified and its genetic sequence was analysed and published by Chinese scientists. This meant work could begin immediately to produce vaccines using the platform technology. It also puts paid to the idea that the virus was a Chinese conspiracy.

The other reasons are due to the huge amounts of money, both public and private, given to fund the trials as well as the number of altruistic volunteer participants. Traditionally, companies would wait until the end of their trials to publish data but instead, they released ‘rolling’ data ‘as it happened’. In the case of BioNTech/Pfizer they were able to publish data in October. Scientists and clinicians at the UK Medicines and Healthcare products Regulatory Agency, (MHRA) were then able to work day and night to scrutinise over 1000 pages of results.

How do we know these vaccines work?

BioNTech/Pfizer enlisted 43,448 people. 21,720 were given their vaccine and 21,728 were given a placebo. 170 participants went on to catch COVID-19. 162 (95%) were in the placebo group. Only 8 (5%) were in the vaccine group. This is where the figure of 95% effectiveness comes from.

Moderna enrolled roughly 30,000 people and again divided participants into those receiving the vaccine and those receiving a placebo. 95 participants in total caught COVID-19, 90 in the placebo group and 5 in the vaccine group. This again gives us a figure of 95% effectiveness.

Oxford-AstaZeneca enrolled over 11,000 people in the UK and Brazil who were either given the vaccine or a placebo. The vaccine group was further divided between people receiving two full doses and those receiving a half dose followed by a full one. The two full vaccine dose regime was found to be 62% effective in preventing COVID-19 while the 1.5 dose regime was found to be 90% effective. The reason for this difference is not yet understood.

Will the new variant make the vaccine pointless?

WGenetic code consists of letters. Whenever genetic material replicates those letters are copied. From that copy, a new genetic code is written. This is called transcription and translation. As when we copy and type out text the odd mistake can happen. Letters can be replaced for another. This can lead to mutations. These can be bad and lead to mistakes which cause cancer. Sometimes the mutation gives the organism a benefit over other organisms, making them more likely to survive and breed and so pass on that advantage. This is the basis of evolution through natural selection.

Viruses are particularly prone to mutation because of how frequently they replicate. Overall, the SARS-CoV-2 virus has shown a low rate of mutations and been quite stable for a virus. Its genetic code consists of 30,000 ‘letters’ and two other mutations had already been identified: one in Spain and one in Danish mink. The Covid-19 Genomics UK (COG-UK) consortium was set up in April 2020 to genetically sequence random positive samples of COVID-19. Since inception, the consortium has sequenced 140 000 virus genomes from people infected with COVID-19.

It was this consortium which picked up a variant of SARS-CoV-2 with 23 mutations, 17 of which may affect its behaviour. One of these mutations causes changes to the spike protein on the virus. As the spike protein is used by the virus to infect cells it is possible that this mutation could make the virus more infectious. This ‘variant under investigation’ has been called VUI-202012/01 or B.1.1.7.

The variant was identified in September and as of 15th December accounted for 20% of viruses sequenced in Norfolk, 10% in Essex, and 3% in Suffolk was likely to have arisen in the UK. It accounted for 62% of new infections in London in the week ending December 9th, up from 28% in early November.

Based on computer modelling it’s been suggested that this new variant is 70% more transmissible than non-variant COVID. The R number, the average number of people every person infected can spread the disease to, seems to be 0.4 higher for the new variant.

Fortunately, one mutation in the spike protein is not likely to render the virus resistant to antibodies generated by the virus so far. However, if sufficient changes to the spike protein were to happen then, yes, the vaccine may be ineffective. This is why we need a different influenza vaccine each year as the influenza virus mutates so quickly.

There is some good news though. Thanks to platform technology we now have a way of quickly producing new vaccines. We have the basics sorted; we would just need to change the mRNA used in the Pfizer and Moderna vaccines or the spike protein expressed in the Oxford vaccine.

Of course, as viruses mutate as they replicate if we reduce cases in the community through vaccination and social distancing we will, as a consequence, reduce the mutation rate.

I’ve seen memes about thalidomide comparing it to these vaccines, how do we know they’re safe?

Just as with any medicine, no vaccine is perfect although as shown above the risks are far outnumbered by those of disease. Thalidomide is not a vaccine, it was marketed in 1957 for morning sickness and discontinued in 1961 due to birth defects. The problem was with the thalidomide molecule and its orientation. The ‘left-handed’ thalidomide was safe, the ‘right-handed’ caused birth defects. This is why it is important to monitor the safety of all medicines.

Medical legislation in this country is incredibly robust; there are 349 individual regulations in 17 parts to make sure any medication, healthcare equipment or vaccine is safe. This includes the reporting of any ill effects. The emergency authorisation is being constantly reviewed and will be rescinded if the vaccine is found to be unsafe.

All of the vaccine trials have been clear when it comes to reporting the rates of adverse reactions to their vaccines. Oxford-AstraZeneca, Moderna and Pfizer/BioNTech have all reported low rates of adverse reactions. The Oxford-AstraZeneca trial was paused due to three adverse reactions: one was in a patient who had not received the COVID-19 vaccine, one had a high fever and it wasn’t known which vaccine they’d received as they were still blinded at that point. One participant who received the COVID-19 vaccine had an inflammation of the spinal cord 14 days after their booster which settled.

The most common ones included pain at the injection site, muscle pains, headache and feeling generally unwell. This is in keeping with any vaccination as those symptoms as a sign of it generating the immune response we want. Last year when I had my influenza vaccine my arm was sore and swelled up at the injection site. This year I felt run down the day after. Both times I took Paracetamol and had a nap. The next day I was fine. Both times were better than having influenza. Having seen the look on patients’ faces struggling to breathe thanks to COVID-19 as they are taken away to be intubated and ventilated I can assure you that the mild side effects of a vaccine are better.

Did we approve this vaccine faster due to Brexit?

In short, no. The UK approved the vaccine before the EU using regulation 174 of the UK’s Human Medicines Regulations, which enables the temporary authorisation of medicine prior to approval by the European Medicines Agency in the case of urgent public need. This Human Medicines Regulations came into effect in 2012, 4 years before the Brexit vote. On top of this EU law allows member states to “temporarily authorise the distribution of an unauthorised medicinal product in response to the suspected or confirmed spread of pathogenic agents, toxins, chemical agents or nuclear radiation any of which could cause harm”. It has nothing to do with Brexit.

I heard this vaccine can’t be stored in most places as it needs to be really cold, is this true?

For long-term storage (about six months) the vaccine has to be kept at -70° C, which requires specialist cooling equipment. But Pfizer has invented a distribution container to keep the vaccine at that temperature for 10 days if unopened. These containers can also be used for temporary storage in a vaccination facility for up to 30 days as long as they are replenished with dry ice every five days. Once thawed, the vaccine can be stored in a regular fridge at 2°C to 8°C for up to five days.

Isn’t natural immunity better?

As far as our bodies are concerned there is no such thing as ‘natural’ immunity. You either develop antibodies through infection or through vaccination. Your body’s response is the same. With infection, you can be seriously unwell as your body’s adaptive immunity kicks in. With vaccination, you develop antibodies without the risks of infection. For example, 0.0001% of patients will experience an adverse reaction to the measles vaccine as opposed to the 0.2% of patients infected with measles who die. The maths is clear.

Don’t vaccines cause autism?

No. The paper which claimed it did was nonsense.

On 28th February 1998, an article was published in The Lancet which claimed that the Measles, Mumps and Rubella (MMR) vaccine was linked to the development of development and digestive problems in children. Its lead author was Dr Andrew Wakefield, a gastroenterologist. The paper saw national panic about the safety of vaccination. Prime Minister Tony Blair refused to answer whether his newborn son Leo had been vaccinated.

However, Andrew Wakefield held a lot back from the public and his fellow authors. He was funded by a legal firm seeking to prosecute the companies who produce vaccines. This firm led him to the parents who formed the basis of his ‘research’. The link between children developing developmental and digestive problems was made by the parents of twelve children recalling that their child first showed their symptoms following the MMR vaccine. Their testimony and recall alone were enough for Wakefield to form a link between vaccination and autism. From a research sense, his findings were formed by linking two events that the parents thought happened at the same time. But the damage was done. The paper was retracted in 2010. Andrew Wakefield was struck off as were some of his co-authors who did not practice due diligence. Sadly, this has only helped Wakefield’s ‘legend’ as he tours America spreading his message tapping into the general ‘anti-truth’ populist movement. Tragically unsurprisingly, often in his wake comes measles.

Last year the largest study to date investigating the links between MMR and autism was published. 657,461 children in Denmark were followed up over several years (compare that to Wakefield’s research where he interviewed the parents of 12 children). No link between the vaccine and autism was shown. In fact, no large high-level research has ever backed up Wakefield’s claim. For a more explicit takedown of common anti-vaccine myths click here.

If we can develop a vaccine for COVID-19 so quickly how come we can’t develop one for HIV?

The human immunodeficiency virus (HIV) is very different from the SARS-CoV-2 virus. HIV infects and destroys helper T cells and so leaves a patient unable to mount adaptive immunity. This means they are vulnerable to opportunistic infections: this is Acquired Immune Deficiency Syndrome (AIDS). Although the virus was discovered in 1984 we are still yet to develop a vaccine. This is because although people infected with HIV do form antibodies (this is how we detect infection) those antibodies are not actually able to kill off the virus. HIV has the ability to hide from our immune system by producing a protein which stops cells it infects from being detected and destroyed. HIV is also able to impair the function of killer T cells. So, even if a vaccine were available which produced antibodies it is unlikely to be able to completely prevent infection.

A much greater success story has been anti-HIV medication which is able to grind HIV replication to a halt, although not completely kill it. Successful antiretroviral treatment can make a patient ‘undetectable’ — it is impossible to detect their HIV in a blood test. This means it is impossible for that patient to pass on their HIV to others. The availability of antiretroviral medication to be given to people at risk of HIV exposure (Pre-exposure Prophylaxis or PrEP) or to people within 72 hours of exposure (Post-exposure Prophylaxis or PEP) can greatly reduce infection rates. Both are nearly 100% effective if taken properly. We’ve been able to turn an infection with a nearly 100% mortality to a manageable, chronic disease in less than four decades. A future without HIV/AIDS is possible but probably won’t involve a vaccine.

I heard these vaccines use nanotechnology to control us

Nanotechnology springs to mind visions of tiny robots swimming in our bloodstream like something from science fiction. Although nanotechnology is real, it doesn’t mean that. ‘Nano’ means ‘one billionth’ or 1 x 10−9. So a nanometre is 0.000000001 metres, a nanosecond is 0.000000001 seconds and so on. Nanotechnology basically means technology which creates, uses or manipulates tiny things on the molecular or atomic level. Nanotechnology in Medicine is also called nanomedicine. As these vaccines involve the use of matter nanometres across such as viruses, mRNA and the participles used to wrap around them they are classed as nanotechnology even though not a single tiny robot is involved.

I heard GPs are being paid to give this vaccine to us

General Practitioners in England are not employed by the NHS. Surgeries are private businesses owned by their partners which the NHS pays to provide services in line with a number of contracts. For providing some services, such as vaccination, the GP surgery charges an ‘item of service’ to the NHS. This fee covers the cost associated with providing the vaccination and is paid by the NHS to practices. It is used to pay for costs associated with providing the treatment.

In a letter sent to GPs on 9 November, NHS England said that it had agreed with the British Medical Association that the “Item of Service fee” for a potential Covid vaccine would be £12.58 per dose (and so £25.16 for a two-dose vaccine such as the one produced by Pfizer and BioNTech). The letter also confirms that the fee for the flu jab will remain £10.06.

So, yes, they are being paid. But it’s not ‘hush money’ or ‘dirty money’ it’s a contracted amount of money for providing a service.

I heard there is aborted fetal tissue in the vaccines

Sigh. This is where a glimmer of fact has been manipulated.

As discussed above the Oxford vaccine uses a chimpanzee virus. In order to propagate the virus, this required what all viruses need to multiply: cells to invade. This meant the study needed cells to use to grow the virus. This is not unique to research involving viruses, a lot of research requires cells. This is when cell lines are used.

Cell lines are mass-produced by taking original tissue and maintained to keep a reliable supply to use in research. Not every cell line lasts. Cells naturally have a ‘senescence’ or ageing process and so will die off. Cell lines are ‘immortalised’ either because they come from tumour cells which through mutation overcome senescence (this is how cancer starts) or because they are altered after being sampled. Each cell line has its own name.

The cell line used to ‘grow’ the chimpanzee virus for the Oxford virus is called HEK293. It is true the original cells for this line came from the kidney of a female fetus which was either lost to miscarriage or medically aborted in the Netherlands in 1973. Researchers used a virus to make the cells immortal and cultured just one bunch of cells. From this bunch of cells came a cell line. This cell line has been maintained ever since as HEK293, as clones of clones of clones of clones of clones etc. over 47 years. The immortalisation process means these cells are not the same as the original sample and the passage of time means those original cells have long gone. The HEK293 cell line was used to ‘farm’ the chimpanzee virus which is then filtered out of the culture. There is no aborted fetal tissue in this vaccine.

It is fair to say that science has a far from innocent record in this area. The first immortalised cell line, HeLa, was taken without consent from an African-American woman called Henrietta Lacks from the cervical cancer which killed her in 1951. As they were tumour cells, they were already immortal and so were cultured to produce a cell line. The HeLa cell line continues to be used in medical research in areas such as cancer treatment and the invention of the polio vaccine. This is the legacy of ‘the immortal Henrietta Lacks’ whose cells continue to live nearly 70 years after she died. However, no consent was sought or compensation given. Her family were not informed of the cell line until 1975. The case of Henrietta Lacks is an example of the need for informed consent in scientific research. It’s also important that scientists follow ethical procedure because, as we’ve seen from Mr (not Dr) Wakefield, they can do a lot of harm.

I heard the vaccines will make you infertile

This just makes me want to…

Right, sorry about that.

OK, let’s take a moment to discuss evidence and science. Let’s say we went up to an astronomer and asked them if the Earth was going to be hit by a comet tomorrow:

Us: “Hi astronomer’.

Astronomer: “Hello (insert name)”

Us: “Is a comet going to hit the Earth tomorrow and wipe out all life?”

Astronomer: “There is no evidence of that happening”.

Us: “What do you mean?”.

Astronomer: “Well, we haven’t picked up a comet on a trajectory with the planet Earth which is big enough to wipe out all life on Earth”.

Us: “So it won’t happen?”.

Astronomer: “There is no evidence a comet is going to hit Earth tomorrow and wipe out all life on Earth”.

Us: “I want definite answers. You’re a scientist, come on, is a comet going to hit us?”

Astronomer: “There is no evidence that will happen”.

Us: “So it could happen?”

Astronomer: “There is no evidence it could”.

Us: “But you’re not certain?”

Astronomer: “I’m a scientist, I look for evidence. We have not found a comet due to hit the Earth so at the moment there is no evidence a comet will hit us tomorrow and wipe us all out”.

Us: “So you’re telling me a comet is going to hit Earth?”

Astronomer: “No, I’m telling you there is no evidence”

Us: “I knew it, we’re all going to die. This is as bad as you guys faking the moon landings”.

Astronomer: “Please leave”.

Scientific proof is not what we think it is. Scientists have ideas or theories and test them. This involves experiments or observation through studies. The results are called evidence. There are levels of evidence which correspond to how ‘good’ a study is based on how it was conducted and how the findings can be applied to other settings. This is fairly obvious: a study conducted in one hospital is not as good as a study involving multiple hospitals across different countries.

Scientists can look at the most recent high-level evidence and draw conclusions based on what best explains what they’ve observed. That is scientific ‘proof’. The theory of evolution best explains the evidence gleaned from fossils, genetic inheritance and DNA. The Big Bang theory best explains the evidence from studying the evolution of stars, galaxies and heavy elements and cosmic microwave background. Observing falling objects and planetary motion is best explained by the theory of gravity. And so on. If observed evidence changes then the theory must change or be rejected for a new one. This is how scientists went from believing the Sun went around the Earth based on the evidence of seeing the Sun move across the sky to believe it’s the other way round. As the famous economist John Maynard Keynes put it so brilliantly:

“When the facts change, I change my mind. What do you do, sir?”

It is the same in Medicine. We’ve seen in patients who take Paracetamol that none of them turns purple with yellow spots. We’ve seen patients who take too much Paracetamol develop liver failure. Therefore, there is currently no evidence that taking Paracetamol makes you turn purple with yellow spots but there is evidence that taking too much Paracetamol causes liver failure.

Somewhere along the line as a society, we have started to demand certainty. We also seem to have somehow reached a point where scientific evidence and personal opinion are now one and the same and can be used interchangeably by members of the public and politicians alike. Scientific evidence is not certain. Nor is it an opinion. It is something which follows a constant process of testing, observing, recording and analysis.

And so back to the question. There is no evidence that the vaccines cause infertility. That’s it.

The building blocks of proteins are called amino acids, and it’s sequences of those that make up different proteins. A small part of the COVID-19 spike protein resembles a part of another protein vital for the formation of the placenta, called syncytin-1. But the sequence of amino acids that are similar in syncytin-1 and the SARS-CoV-2 spike protein is quite short and not the whole protein. They are not the same.

Therefore realistically the body’s immune system is not likely to confuse the two, and attack syncytin-1 rather than the spike protein on SARS-CoV-2 and stop a placenta forming.

This claim came from concerns that the COVID-19 spike protein the vaccines make the body produce antibodies against also contain “syncytin-homologous proteins, which are essential for the formation of the placenta in mammals such as humans”. The authors: Dr Mike Yeadon in the UK, who has made a name for himself as a contrarian to the scientific consensus during the pandemic and Dr Wolfgang Wodarg from Germany, who has a history for casting doubt on everything from pandemic definition to vaccine production demanded that it must:

“be absolutely ruled out that a vaccine against SARS-CoV-2 could trigger an immune reaction against syncytin-1, as otherwise, infertility of indefinite duration could result in vaccinated women”.

As we’ve just discussed, no one seriously wanting scientific evidence would make such a request for absolute proof. An actual scientist would think about this problem. Infected patients produce antibodies just as vaccinated people do. Is there any evidence that infected women lose their pregnancy?

This study of 225 women in their first trimester found no increase to early pregnancy loss in those infected with COVID-19. This study compared 113 women pregnant in May 2020 to 172 pregnant in May 2019 and found no increase in pregnancy loss. This study looked at 252 pregnant women infected with COVID-19 found no increase in adverse pregnancy outcomes.

There is no evidence that the vaccine causes infertility or miscarriages. A couple of attention-seeking ‘truth seekers’ have lit a bin fire and left the serious medical profession to put it out. With that in mind, I am fed up with members of my own profession talking far outside of their area of expertise, cynically or otherwise, during the pandemic and helping to fuel mistrust at a time when we should have stood together. But that’s a blog for another day.

I heard that the vaccine companies can’t be sued if things go badly

Wrong. A government consultation document laid out proposals to potentially authorise a vaccine for emergency use. Existing UK law (as informed by EU law) says that if the government decided to do this, manufacturers and healthcare professionals would not take responsibility for most civil liability claims. But, if the vaccine is found to be defective or not meet safety standards then:

“the immunity does not apply…(and) the UK government believes that sufficiently serious breaches should lead to loss of immunity”

If the vaccines are found to be dangerous or defective you can guarantee that the companies involved will be sued until their pips squeak.

There. I hope this has made sense. Thanks to everyone who reached out and asked questions. I appreciate that this will not be enough for the conspiracy theorists who will say everything I’ve put here is a ‘point of view’ as valid as their memes. For the rational majority, I hope it has answered those questions and any lingering doubts. It has been a strange year and it has never been easier to spread lies. Fortunately, it’s never been easier to spread the truth.

http://JamesThomas.me Doctor and Educator. Podcast https://www.takeaurally.com Blog on Medical Education and History of Medicine https://mcdreeamiemusings.com