Barts-MS rose-tinted-odometer: ★★★★★
Just to let you know that the I have answered all the reasonable questions that have come in via the COVID-19 decision aid. To keep it simple and to allow me to be more responsive I will simply update the online document every day or so. This is similar to what I did with the MS-Selfie Microsite I ran for at the beginning of the pandemic.
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
Barts-MS rose-tinted-odometer: ★★★★★
Thank you for the feedback on my rough-and-ready decision aid. It is clear there is a need for it. I have spent a bit of time adding DMT-specific pages to the aid and added sections on ‘Which vaccine?’ and ‘Pregnancy’. I have also added a page with useful links. I have also set the sound to be on-demand rather than being automatic; so you need to click on the icon if you want to hear me talk to the question or topic on a specific slide.
Please note this is still a beta version, albeit version 2.0, using the Google Slide’s technology as an easy-to-use platform for prototyping. I will continue to update the decision aid as questions come in. The survey results are quite telling in that you prefer a text document in a downloadable format and a web application. Now I need a grant to be able to pay our ClinicSpeak design team to make this beautiful and more user-friendly.
Your feedback is very much appreciated so keep the comments coming in. Thanks.
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
Barts-MS rose-tinted-odometer: ★★★★★
What is vaccination? A not so simple medical procedure.
Vaccination is probably one of, if not, the most important scientific/medical inventions in modern history. We need to celebrate it for just that and appreciate the number of saved lives and improved quality of life it has brought to us as a species.
Now that we broadly know how the immune system functions there is nothing magic, dark or sinister about vaccines and vaccinations work.
Vaccines simply hijack components of the immune system and fool it into thinking you are being invaded by something foreign and dangerous, e.g viruses, bacteria, parasites, toxins, cancers or foreign bodies. The immune system reacts to the vaccine and rejects the foreign component in the vaccine, but in doing so the immune system remembers the foreign component so in the event of being exposed to it again in the future it can respond to it quickly and prevent it causing too much damage, i.e. disease or some cases death.
The immune system is primarily responsible for keeping us safe from infectious agents, i.e. parasites (e.g. malaria), bacteria (e.g. pneumococcus) and viruses (e.g. coronaviruses), toxins and cancer. Immune systems are endowed with the ability to remember a previous exposure to an infectious agent.
Immunological memory is hardwired into our DNA, which includes so-called pathogen-associated or damage-associated recognition receptors (PAMPs or DAMPs). PAMPs and DAMPs are part of our innate immunity and provide a very rapid response to infections. However, as there is an arms race between our immune system and the pathogens, which can mutate and evolve very quickly (e.g. the UK/Kent, South African and Brazilian variants of SARS-CoV-2), we have had to evolve a second or an acquired memory system called adaptive immunity. The latter involves both B-cells or antibodies and T-cells or killer cells that are able to destroy the pathogen using highly targeted mechanisms that in most people don’t cause collateral damage to the body.
All that a vaccine does is expose the immune system to a part of the whole of the pathogen in the correct context so the immune system remembers the pathogen so that when it is exposed to the pathogen in real-life it can mount a rapid immune response, which prevents you becoming infected and spreading the organism, or prevents you from getting a severe disease or dying from the infection.
Now there are many different ways of fooling the immune system into remembering the organism. In the past, we used to use related, but benign, viruses. For example, immunity to cowpox, a live virus from cows, cross-reacted with the more dangerous and severe smallpox virus to protect milkmaidens from getting smallpox. This is how Jenner identified and created the original smallpox vaccine. Following Jenner’s smallpox vaccine, the scientific community developed the ability to attenuate viral and bacterial strains in the laboratory, i.e. to create mutant strains that didn’t cause disease, but were similar enough to the original organism to generate a protective immune response. This is how the medical community tackled polio, measles, mumps, rubella, TB, yellow fever and influenzae. This group of vaccines are referred to as LAVs or live-attenuated vaccine strains.
The problem with LAVs is that the organisms have the ability to mutate back to being dangerous and can cause vaccine strain outbreaks, which has happened many times with the oral polio vaccine. This is why LAVs have in general fallen out of favour. I am not aware of any LAVs being developed for coronavirus; mainly because it is an outdated technology.
Another way of developing vaccines is to grow the organism in the laboratory and then inactivate or kill them and then to administer either the whole killed organism or a part of it as a vaccine. This is how the seasonal flu virus is currently made. The current circulating strains are cultured in chicken eggs and then the eggs are broken and processed to extract the important surface proteins to go into the vaccine. One of the Chinese vaccines that is currently been tested in COVID-19 uses the whole SARS-CoV-2 virus as an immunogen.
The term immunogen simply refers to the component of the vaccine you want the immune system to respond to, for example, the spike or surface protein on the coronavirus. When we make vaccines that only have one or a limited number of immunogens we call this a component vaccine.
Now that we have developed so recombinant protein technology we don’t have to culture live and often very dangerous organisms, but instead engineer other organisms to make the immunogen in large quantities. To do this we alter the genomes of bacteria, mammalian cells, whole animals or even plants to make the protein we want. For example, we can use E. coli bacteria, Chinese hamster ovarian cells, monkey cells or even insect cells to make proteins. The choice of the type of cell is important as many immunogens have sugar molecules on them and cells from different species add sugar molecules in different configurations and combinations. E. coli, for example, does not have the necessary molecular pathways to add sugar molecules to proteins.
A, relatively, new technology is to create genetically modified whole complex organisms that produce your protein of choice. One vaccine company has created a tobacco plant that produced the protein for the hepatitis B vaccine. You then grow the tobacco plant and extract the hepatitis B surface antigen from tobacco leaves. Another company has created a breed of goat that expresses and produces the vaccine immunogen in breast milk. All you have to do is milk these goats and extract the immunogen from their milk.
Many of the SARS-CoV-2 component vaccines are using standard cell-based methods to produce vast quantities of the immunogen, which at present are mainly targeting the SARS-CoV-2 spike protein. The recent positive Novavax coronavirus vaccine is using spike protein manufactured using insect cells.
Component vaccines are not that immunogenic unless they are combined with an adjuvant. Adjuvants are substances that enhance the immune system’s response to the vaccine. Adjuvants are often referred to as the immunologist’s dirty little secret. The reason for this is we simply didn’t know how many of the early adjuvants worked. This is not the case anymore and the newer generation of adjuvants that are being used in component vaccines are well defined in terms of their mode of action and are safe.
Some scientists have used molecular biology to engineer other relatively benign viruses so that they make immunogens of other viruses. Instead of making the protein in the laboratory, you produce infectious viruses, that then make the protein in your body. You infect people with these engineered viruses, which are also called vectors, as part of the benign infection your own cells make the protein or immunogen that your immune system then responds to.
Vaccinia virus used to be the most commonly used virus, but vaccinologists have moved onto adenovirus one of the viruses that cause the common cold. The Russian sputnik COVID-19 vaccine uses a human adenovirus as the vector. The Oxford-AstraZeneca vaccine uses a chimpanzee adenovirus vector. The problem with using these types of vaccines is that if your immune system has seen the virus in the past, i.e. from natural wild-type viral infection, your immune system reacts to and rejects the vaccine virus before it can infect enough cells to make the necessary quantity of immunogen to be effective. This is why the Oxford-AstraZeneca vaccine uses a chimpanzee adenovirus, which humans are unlikely to have been exposed to in the past. The immune response to the vector itself has implications for booster and additional vaccine using the same technology; i.e. it is likely that boosters and new vaccines using the same vector will be less effective in the future, because of immunity against the vector itself.
Please note these viral vector vaccines are relying on the virus to infect cells and then use the cells own machinery to manufacture the immunogen. Because these vaccines are an actual infection these vaccines don’t need adjuvants. The final trick with these viral vector vaccines is to create disabled viruses, i.e. viruses that lack the ability to replicate and cause ongoing infection. This is important to prevent the viral vector itself causing an infection in the host or recipient of the vaccine. This is also the reason why the Oxford-AstraZeneca vaccine is not referred to as a live viral vaccine.
Finally, why waste time with viruses and simply give the viral message without the virus. This is how DNA and RNA vaccines work. You package the necessary code for the immunogen in a DNA plasmid or piece of RNA that is then transcribed into the necessary proteins to induce an immune response.
Do RNA and DNA vaccines need adjuvant? The cell sees foreign RNA itself as being foreign as being potentially from a virus, which acts via internal danger signalling pathways to alert the immune system to the possibility of an infection. The DNA vaccines incorporate segments of DNA that fool the cell into thinking this DNA is from a bacterium, which also stimulates specific danger signalling pathways telling the immune system there is an infection. This is why RNA and DNA vaccines don’t require additional adjuvants.
Please be aware that adenoviral vaccines, such as the Russian Sputnik and the Oxford-AstraZeneca vaccines, the DNA vaccine and the RNA vaccines don’t contain the code for manufacturing the necessary enzymes that insert DNA into the genome. The latter is unique to so-called retroviruses such as HIV. Therefore, these coronavirus vaccines don’t affect the human genome and won’t affect the germline, i.e. DNA transmitted via the eggs in the ovary of the sperm in the testes. All that these vaccines do is highjack the cells protein synthesis machinery to make SARS-CoV-2 spike protein and to tell the immune system that there is an infection. This then allows the immune system to make both B-cell or antibody and T-cell responses to coronavirus and protect that individual from being infected or becoming ill from wild-type infection.
I want to stress that the short summary above represents centuries of research and discovery and that vaccinology is now using cutting edge molecular biology. The rapid development of the DNA, RNA and adenoviral vector vaccines have changed vaccine development for good and I anticipate these becoming the norm for future vaccines.
I hope the above summary explains how vaccines have developed and debunks the myths about what they are and how they work. Instead of us accepting off-the-wall conspiracy theories about vaccines and what they do please join me in celebrating their success and what they offer mankind.
One of my driving ambitions is to see an EBV vaccine licensed to prevent MS. If you and the general population are not prepared to trust vaccines and the science behind their development, who is going to want their child to have an EBV vaccine to prevent MS, infectious mononucleosis and many different types of EBV-associated cancers?
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
Barts-MS rose-tinted-odometer: ★★★★★
The horse’s mouth = the MHRA (Medicines and Healthcare products Regulatory Agency)
I have received several vexatious emails accusing me of subjecting my patients, and people with MS (pwMS) in general, to an experiment by recommending and promoting the COVID-19 vaccines. I want to remind the readers that we need to listen to experts. I was challenged that may be the experts are wrong. So if the experts are wrong which regulators should I challenge first; the FDA, EMA, MHRA, Russian, Swiss, Japanese, Canadian, etc.? Have they all got it wrong?
Yes, occasionally a single regulatory authority may get things wrong, but they have checks and balances in place to correct their errors. As so many regulatory authorities have approved these vaccines is very telling. In addition, for most of the regulatory authorities above their approvals have been unanimous, i.e. all the experts and representatives on their panels have agreed that the safety and efficacy of the COVID-19 vaccine warrant their emergency marketing authorisations.
Some of these vexatious commentators state that these vaccines were developed too quickly. Yes, they were developed quickly, but not too quickly. The platforms used for these vaccines were already in place and all that had to be done was to slot in the SARS-CoV-2 spike protein immunogen, tweak the production methods and the vaccines were ready for mass production. For the Oxford-AstraZeneca vaccine, all they had to do was swap out the sequence for the coronavirus that causes MERS for SARS-CoV-2. The latter process happened within a week or two.
Instead of doing trials in series a lot of the clinical development was done in parallel, i.e. phase 1b/2 immunological studies were done as part of phase 2 trials and phase 3 studies were added-on in an adaptive way to phase 2 trials. The reason for this turbocharging or the development pathway was that governments had derisked the development of the vaccines and given money to the companies to develop and test vaccines. In parallel governments also provided capital to build production facilities etc.
So in summary the vaccine development programme was sped up by capital and contracts by governments for a defined number of orders. In normal times this does not happen, hence the many years it ‘normally takes’ to develop a vaccine. In my opinion, no short-cuts were made in terms of testing these vaccines for safety and efficacy. In fact, one could argue that the COVID-19 spike protein vaccines, as a body, represent the largest safety trial programme in vaccine history.
Now that the vaccines have been used on millions of people if there were any rare sinister adverse events we would have expected the regulatory agencies to have reported them. And yes they have. The only one that sticks out from the Israeli and UK experiences is Bell’s palsy, as a rare adverse event, with the Pfizer-Biontech and probably the AstraZeneca-Oxford vaccine as well.
I would like to remind these vexatious commentators that there is no conspiracy theory behind the COVID-19 vaccines and vaccination programmes. What public health officials are doing is simply trying to save lives, protect healthcare services and to stop the pandemic.
Dare I suggest that the ‘post-truth era’ is coming to an end and that politicians, patients and the public will start to value experts again? As a society, we spend an extraordinary amount of time and money to educate and train experts to manage and run institutions such as the FDA, EMA, MHRA, CDC, WHO, etc. These experts need to be trusted and respected; all they are doing is what they have been asked by us to do.
We all have a responsibility to act responsibly and to not dismiss COVID-19 vaccines as being ineffective, unsafe and designed to anything else other than what is in their labels. In general, these vaccines are very effective, safe and reduce your chances of getting severe COVID-19 and dying from COVID-19 by well over 95%. Why wouldn’t you want the vaccine?
Ingrid Torjesen. Covid-19: First UK vaccine safety data are “reassuring,” says regulator. BMJ 2021; 372 doi: https://doi.org/10.1136/bmj.n363 (Published 08 February 2021)
Excerpts:
… The UK’s medicines regulator has described the first safety data related to covid-19 vaccines as “reassuring,” with most side effects reported being mild and in line with those seen with other types of vaccine. “The benefits continue to far outweigh the risks,” said June Raine, chief executive of the Medicines and Healthcare Products Regulatory Agency (MHRA).
… The agency published yellow card data for covid-19 vaccines given between 9 December 2020 and 24 January 2021, which comprise 22 820 reports from 7 164 387 first doses and 474 156 second doses. Most of the reports (16 756) are from people who received the Pfizer-BioNTech vaccine, and these list 49 472 suspected reactions. Administration of the AstraZeneca-Oxford vaccine began later, on 4 January, and 6014 yellow cards were reported up to 24 January, detailing 21 032 suspected reactions. A further 50 yellow card reports did not specify the brand of vaccine.
… By 24 January an estimated 5.4 million first doses of the Pfizer-BioNTech vaccine and 1.5 million doses of the AstraZeneca-Oxford vaccine had been administered, and around 0.5 million second doses, mostly of the Pfizer-BioNTech vaccine. Overall, the data show around three yellow card reports per 1000 doses of the vaccine given—a smaller proportion than the 10% of patients reporting them in clinical trials.
…. Severe allergic reactions were reported after administration of the first doses of the Pfizer-BioNTech vaccine on 9 December. Subsequently, the MHRA advised against its use for people with a history of severe allergic reactions to any ingredients in the vaccine and said that recipients should be monitored for at least 15 minutes.
…. A total of 101 anaphylaxis or anaphylactoid reactions after the Pfizer-BioNTech vaccination (1-2 cases per 100 000 doses) have been reported to the MHRA up to 24 January, and 13 anaphylaxis reactions after the AstraZeneca-Oxford vaccine.
….. Bell’s palsy is listed as a possible side effect of the Pfizer-BioNTech vaccine, and facial paralysis or paresis after this vaccine was mentioned in 69 yellow card reports; facial paralysis was mentioned in six reports after the AstraZeneca-Oxford vaccine. Philip Bryan, vaccine safety lead at the MHRA, said, “Bell’s palsy is something that can also happen naturally, so its association with the vaccine hasn’t been established.”
… The MHRA received 107 reports of death after the Pfizer-BioNTech vaccine, 34 after the AstraZeneca-Oxford vaccine, and 2 in which the brand of the vaccine was unspecified. Most reports were for older people or people with underlying illness, the MHRA said, and a review of individual reports and patterns of reporting did not indicate that the vaccine played a role in the death. “We know, for instance, based on data from [the Office for National Statistics], that for every 100 000 doses given to people aged 80 or over, around 200 people die of natural causes within a week,” Bryan said.
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
Barts-MS rose-tinted-odometer: ★★★★★
Despite the long blog post that I called CATCH-22 I am still getting numerous emails and questions from patients with MS about whether or not they should have a COVID-19 vaccine.
YES, you should have the vaccine when it is offered to you. Clearly, timely access to the vaccine will depend on where you live, how vulnerable you are and the local, regional and national guidelines in place in your own country.
The benefits of COVID-19 vaccination is time-sensitive and if you wait to be vaccine-ready you may inadvertently acquire the coronavirus infection and become really ill or when you are vaccine-ready the pandemic and the at-risk period may have passed.
In my opinion, some immunity is better than no immunity and the blunted vaccine immunity on some DMTs may be sufficient to prevent you from becoming infected with SARS-CoV-2, developing COVID-19 and more importantly developing severe COVID-19.
Are the vaccines safe? No vaccine is 100% safe, but the fact that the regulatory authorities have licensed these vaccines indicates that the benefits of the vaccine far outweigh the risks associated with the vaccine in the general population. At the moment the only relative contraindication to the Pfizer-BioNTech RNA vaccine is a history of severe atopy or allergies, i.e. people who carry around an epi-pen to prevent anaphylaxis in response to an environmental allergen.
If you have any questions please read the CATCH-22 blog post, and our new advice here. If these don’t answer your question(s) we will try and address them below.
Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
Barts-MS rose-tinted-odometer: ★★
“I think the people of this country have had enough of experts”, Michael Gove, June 2016.
Of the many positive things to come out of the COVID-19 pandemic and our response to it is the end of the era of denigrating the expert. Yes, expertise and in particular deep expertise really matters and that applies to the diagnosis and management of multiple sclerosis.
What is the difference between expertise and deep expertise? For example, I am registered by the General Medical Council in the UK as a neurologist and hence a medical expert in the practice of neurology. This means I can see, diagnose and manage anybody with a neurological problem. However, my sub-speciality is multiple sclerosis and related diseases (deep expertise). If you had a myopathy or a disease of muscles would really want me to be your treating neurologist. I suspect not; you would probably want to see a neurologist who specializes in muscle diseases. Although, I can quite easily read about the latest evidence and research into myopathies and give you an expert opinion, as I don’t have the day-to-day experience (deep expertise) in managing patients with myopathy you would not be given the best advice. Who knows if my self-directed rapid myopathy update would be good enough? Would I have enough insight and experience to only read the best most up-to-date evidence or would I be influenced by some whacky off-the-wall myologist (muscle expert)?
We need, more than ever, a serious pushback on ‘fake news sites’, ‘lobby groups with vested interests’, ‘social media groups without expert input’ and ‘anti-science movements with unsubstantiated conspiracy theories’ to name the most obvious.
We also need to understand and learn to live with and be comfortable with uncertainty. Yes, that means accepting that experts may disagree with each other. Science is not black-and-white and is usually grey and as more evidence emerges and innovations or ideas become adopted or accepted the colour or advice becomes closer to being black or white. Science and the acceptance of science take time.
This is where inspired leadership comes into play. In any field, there are leaders who have the necessary reputations and trust that people will follow their advice. These leaders are often good communicators and have the uncanny ability to provide a balanced view of the state of play when the evidence is not black-and-white and they can communicate uncertainty in a way that makes sense and is understandable to the general public. Dr Anthony Fauci, from the NIH, comes to mind with his level headed approach to the COVID-19 epidemic in the US. On the other hand, there are many examples of bad or poor leadership during this pandemic, which has resulted in squandering of political capital, confusion and lack of trust. I don’t think I need to give specific examples of poor leadership there are many obvious ones.
In the MS space, there is different advice being peddled by various groups about what to do about vaccinating people with MS on anti-CD20 therapies with the newly licensed or soon to be licensed coronavirus vaccines. I think there is broad consensus that a live replicating viral vaccine is a no-no in people on anti-CD20 therapies. However, this advice is irrelevant as the three coronavirus vaccines at the head of the queue are not live replicating virus vaccines. The Oxford-AstraZeneca vaccine uses a viral vector (chimpanzee adenovirus) to deliver the construct (nucleotide message) to express the immunogen, but it is a replication-deficient virus so is highly likely to be safe in people with MS on anti-CD20 therapies.
Another bit of misinformation that is doing the rounds is that these vaccines will trigger MS relapses. This is based on extrapolating data on two non-peer-reviewed cases of CNS demyelination in the Oxford-AstraZenca (Ox-AZ) trial and several cases of transverse myelitis in patients who have had COVID-19. One case on in the Ox-AZ trial, who received the vaccine, had an initial attack or relapse and was subsequently diagnosed as having MS; i.e. assume because they had pre-existing lesions and were now shown to have a second attack or new lesions consistent with dissemination in time. The other case had an episode of vaccine-related transverse myelitis (TM), which is relatively common with vaccines in general. Please note that vaccine-related TM is not MS. The only vaccine that has been reported to potentially trigger MS relapse is the live yellow-fever vaccine and this is based on one report that has subsequently not been replicated. Therefore, there is no current evidence that coronavirus infection or coronavirus vaccines trigger MS relapse. This in my opinion is not a reason to avoid having the coronavirus vaccine at present. This opinion may change if new data emerges to the contrary.
Another bit of grey advice that is being peddled as black or white is that people with MS (pwMS) on anti-CD20 therapy should delay their next infusion or miss one or two infusions to allow B-cell reconstitution before they have a coronavirus vaccine. What is the evidence for this? There is no definitive evidence. Yes, I agree that in general people on anti-CD20 therapies have blunted antibody responses to wild-type SARS-CoV-2 infection and to other vaccines including vaccines with so-called neoantigens or new antigens that the immune system has not seen before. However, this doesn’t mean these people haven’t developed immunity to the infection of vaccine that is long-lasting. For one the vast majority of pwMS on an anti-CD20 therapy who get COVID-19 make an uneventful recovery. Why? Almost certainly this recovery is due to cellular and not humoral (antibody) immunity. Do you then think this cellular immunity simply vanishes? Highly unlikely. Normal people who have COVID-19 and who lose their antibody responses still have cellular immunity. My interpretation of this data is that pwMS who are on an anti-CD20 therapy should simply go ahead and have the coronavirus vaccine when it is offered to them and not to worry about whether or not they mount an antibody response. Whilst this is happening companies like Roche-Genentech (ocrelizumab & rituximab) and Novartis (ofatumumab) or the wider MS community should be funding studies to look at both antibody and cellular immunity to the coronavirus vaccines in pwMS on these therapies so that we can develop an evidence base. The data collected as part of these studies will not only be relevant to SARS-CoV-2 infections and vaccines but other infections and future vaccines.
In my opinion, it is more important for pwMS to be vaccinated than to not be vaccinated. This is because vaccination policy is really about population, or subpopulation, health and stopping the spread of the virus and protecting the individual is a secondary aim. If you have MS and would rather wait for data to emerge on the safety and efficacy of the vaccine in the MS population it will take another 6 to 12 months, and maybe longer, and then the evidence if not collected prospectively as part of a well-controlled trial may not answer the questions you have. Also in 6-12 months, the pandemic is likely to be over and hence these questions may never get answered.
So my gut feeling based on scientific principles is that all pwMS should be vaccinated. If the initial roll-out of vaccines means the vaccines may be rationed I would argue we prioritise pwMS (1) over the age of 50, (2) those with significant comorbidities, (3) those on immunosuppressive therapies, in particular, those on anti-CD20 therapies and natalizumab and (4) those pwMS doing essential jobs with significant face-to-face contact with the general public (healthcare workers, care workers, teachers, etc.) to get the vaccine first.
Disclaimer: As I am not a public health or vaccine expert you need to interpret my advice with care.
Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211
Barts-MS rose-tinted-odometer: ★★★★★
I think COVID-19 has just cancelled the flu season.
I and many public health officials were very concerned that we were heading for a double-whammy this winter with a second and third surge of COVID-19 and a bad influenzae pandemic superimposed on it. It is looking like this may not happen. In the Southern hemisphere, including my country South Africa, it seems as if the flu season was cancelled. Incredibly the number of documented annual cases has dropped by over 99% (see table below).
| Country | 2018 | 2019 | 2020 |
| Argentina | 1517 | 4623 | 53 |
| Chile | 2439 | 5007 | 12 |
| Australia | 925 | 9933 | 33 |
| South Africa | 711 | 1094 | 6 |
It is clear that the behavioural changes we have put in place, such as social distancing and wearing of masks, has prevented the spread of influenzae virus. Will these behaviours become the new norm during future flu seasons? I am not sure if people realise that influenzae is one of the biggest infectious disease killers each year so preventing the spread of the virus via behavioural change makes sense.
Saying this the UK Government has just ordered many more doses of influenzae vaccines than it normally does and is extending the so-called at-risk adult group who can get the vaccine free on the NHS this year.
Does this change our recommendations regarding getting the annual flu-jab? No, it doesn’t. All pwMS should take up the offer by the NHS to get the annual flu vaccine.
Please note, if you are severely immunosuppressed and have small children, please make sure they don’t get the live intranasal flu vaccine at school. There is a risk that this attenuated vaccine strain, which they may bring home, will cause disease in severely immunocompromised subjects. If you want your children to be vaccinated against influenza they will need to be given the component vaccine by injection. The latter is done via GP practices and some pharmacists. Please note it is only patients recently treated with alemtuzumab and HSCT that fall into this category.
I suspect that after reading the post on complications in the Oxford-AstraZeneca coronavirus vaccine study many of you are nervous about vaccinations in general. Please don’t be. The regulatory authorities assess the efficacy and safety of all vaccines and make an informed decision that at a population level the risks justify the benefits. Influenzae vaccination is the most studied vaccine in pwMS and it has been shown to be safe, i.e. it does not appear to trigger relapses and/or MRI activity.
CoI: multiple
Twitter: @gavinGiovannoni
Medium: @gavin_24211
You will have heard by now that AstraZenca has paused its coronavirus vaccine study because of safety concerns. A study subject who received the vaccine developed transverse myelitis and had to be admitted to hospital.
“The woman’s diagnosis has not been confirmed yet, but she is improving and will likely be discharged from the hospital as early as Wednesday”, said Soriot AstraZenca’s CEO (source STAT News).
From the same press conference, we also found out that another study subject had developed multiple sclerosis after receiving the vaccine. As most of you are aware transverse myelitis may be the initial manifestation of MS and sometimes it is very difficult to differentiate non-MS related transverse myelitis from CIS (clinically isolated syndrome compatible with demyelination or MS).
Are two swallows enough to make a summer? I suspect not and I would be surprised if the data and safety monitoring committee recommends stopping the trials. However, they may do so if there is a third or fourth case.
Transverse myelitis (TM) is well described after vaccination as well as after viral and other infections. The yellow fever vaccine is probably the most common cause of vaccine associated TM. However, it was a common adverse event with the original rabies vaccine that was cultured and isolated from monkey neuronal cells. Fortunately, this is not how the rabies vaccine is made anymore and the incidence of TM is now much less common after rabies vaccination. Other vaccines that can trigger TM are influenzae, MMR, Japanese B encephalitis, hepatitis B and HPV vaccines. TM has also been associated with many infections, particularly viral and some bacterial infections. We neurologists refer to this type of TM as being vaccine-associated or post-infectious TM, respectively.
Even if the AstraZenca vaccine trials restart, which in my opinion is likely, and the vaccine is shown to be effective, it is likely that the regulatory authorities will include TM as a potential adverse event. The latter will be based on the recent case and the historical perspective of other vaccines being known triggers of TM. What they will do about the case of MS is anyone’s guess, but I suspect they will include triggering MS disease activity as a potential adverse event as well. If they do this this will cause the MS community to probably err on the side of safety and hence this particular coronavirus vaccine will not be recommended for people with MS.
Other implications is that there is a chance that the TM has not been induced by the Chimpanzee Adenovirus vector that is being used in this vaccine, but the actual coronavirus spike protein or immunogen. It is noteworthy that several cases of COVID-19 related TM have already been reported in the literature (see below), suggesting it may be the virus or the spike-protein that is the culprit. If this proves to be the case then it is really bad news as TM will be a problem for the whole class of vaccines using the spike protein as the immunogen.
So the implications of these observations are enormous for the field. However, there are things that can be done by neuroimmunologists to study the immune response to the SARS-CoV-2 spike protein and the Chimpanzee Adenovirus vector to see if there is any cross-reactivity with proteins and lipids in the spinal cord. The latter are standard molecular mimicry studies and this could help AstraZeneca and other vaccine manufacturers understand the TM risk in more detail.
You have to realise that this is what happens with vaccine and drug development and underscores why drug and vaccine development is so risky and expensive. The investment costs in terms of this vaccine have been largely derisked for AstraZenca by most of the preclinical development being funded and done by academia and the fact that the British and other governments have pre-ordered millions of doses of vaccine.
We will update you on this story as it evolves.
Addendum: the published case reports of TM-like conditions occurring in association with COVID-19.
| 1. | Acute transverse myelitis after COVID-19 pneumonia.Munz M, Wessendorf S, Koretsis G, Tewald F, Baegi R, Krämer S, Geissler M, Reinhard M.J Neurol. 2020 Aug;267(8):2196-2197. doi: 10.1007/s00415-020-09934-w. Epub 2020 May 26.PMID: 32458198 Free PMC article. No abstract available. |
| 2. | Transverse Myelitis in a Child With COVID-19.Kaur H, Mason JA, Bajracharya M, McGee J, Gunderson MD, Hart BL, Dehority W, Link N, Moore B, Phillips JP, Rogers D.Pediatr Neurol. 2020 Jul 29;112:5-6. doi: 10.1016/j.pediatrneurol.2020.07.017. Online ahead of print.PMID: 32823138 Free PMC article. No abstract available. |
| 3. | Acute transverse myelitis in COVID-19 infection.Chow CCN, Magnussen J, Ip J, Su Y.BMJ Case Rep. 2020 Aug 11;13(8):e236720. doi: 10.1136/bcr-2020-236720.PMID: 32784242 Free PMC article. |
| 4. | COVID-19-associated acute transverse myelitis: a rare entity.Chakraborty U, Chandra A, Ray AK, Biswas P.BMJ Case Rep. 2020 Aug 25;13(8):e238668. doi: 10.1136/bcr-2020-238668.PMID: 32843475 Free PMC article. |
| 5. | Transverse myelitis related to COVID-19 infection.Zachariadis A, Tulbu A, Strambo D, Dumoulin A, Di Virgilio G.J Neurol. 2020 Jun 29:1-3. doi: 10.1007/s00415-020-09997-9. Online ahead of print.PMID: 32601756 Free PMC article. No abstract available. |
| 6. | COVID-19-associated acute necrotizing myelitis.Sotoca J, Rodríguez-Álvarez Y.Neurol Neuroimmunol Neuroinflamm. 2020 Jun 10;7(5):e803. doi: 10.1212/NXI.0000000000000803. Print 2020 Sep.PMID: 32522767 Free PMC article. No abstract available. |
| 7. | Acute necrotizing myelitis and acute motor axonal neuropathy in a COVID-19 patient.Maideniuc C, Memon AB.J Neurol. 2020 Aug 9:1-3. doi: 10.1007/s00415-020-10145-6. Online ahead of print.PMID: 32772172 Free PMC article. |
| 8. | A case of possible atypical demyelinating event of the central nervous system following COVID-19.Zoghi A, Ramezani M, Roozbeh M, Darazam IA, Sahraian MA.Mult Scler Relat Disord. 2020 Jun 24;44:102324. doi: 10.1016/j.msard.2020.102324. Online ahead of print.PMID: 32615528 Free PMC article. |
| 9. | Acute transverse myelitis associated with SARS-CoV-2: A Case-Report.Valiuddin H, Skwirsk B, Paz-Arabo P.Brain Behav Immun Health. 2020 May;5:100091. doi: 10.1016/j.bbih.2020.100091. Epub 2020 Jun 6.PMID: 32835294 Free PMC article. |
CoI: multiple
In clinic yesterday a patient told me that a vaccine post they read on the blog was very confusing. After reading it they didn’t know what to do. It is important to emphasise that this blog is primarily about MS research and not necessarily about clinical advice. I always tag my clinical posts with the hashtag #ClinicSpeak. In future, I will also colour code them. Will this help?
The following vlog is some off the cuff advice about vaccines. I hope this clears up some of the confusion.
Adding to this Post By ProfG and relevant to todays post.
Genetic evidence for a case of re-infection with SARS-CoV-2. Tillett et al. SSRN-id3680955.pdf Here is a case where re-infection can be shown to occur as the person had two different strains of the virus. Perhaps the bad news whilst the first infection was mild was that the second round of infection was associated with hospitalization showing that infection with the virus does not give 100% protection. This could be uncommon but we cannot say this and it may not be.
CoI: multiple
It is one thing calling for scientists to turbocharge the development of a coronavirus vaccine but quite another to get the population to have the vaccine. The anti-vaxxers are organising rapidly and have started circulating content with false information to achieve their aims. The movie plandemic is one example and is covered in a very good article in the New York Times today.
The primary reason I started this blog was to counteract anti-science movements and to provide people with MS and their families a rational interpretation of MS-related research. It is interesting to note that there is now good data science to show how anti-science movements, despite having very few initial supporters, get their message across and sow enough confusion to get undecided people to support their movement.
What I find fascinating, albeit scary, is how dynamic and multifaceted the anti-vaccination campaigns are, which explains their explosive growth in recent times (see figure and paper below). It also shows how gullible people are in general. The study below highlights why we scientists need to fight back using the same tactics. Simply sitting in our ivory towers using traditional media and unidirectional channels will not be good enough to fight the anti-vaccination and other anti-science movements.
I have a vested interest in this. One of our lines of research is to use an anti-EBV vaccine to prevent MS. If people don’t want vaccines how are we going to get this prevention strategy adopted by funders, ethics committees and more importantly the general population?
Can you help? Yes, please help fight fake news, by reporting it and calling it out for what it is. And don’t believe the fabricated conspiracy theories that are peddled to support these anti-science movements. The vast majority of conspiracy theories are wrong.
Johnson et al. The online competition between pro- and anti-vaccination views. Nature published: 13 May 2020
Distrust in scientific expertise is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks, as happened for measles in 2019. Homemade remedies and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice. There is a lack of understanding about how this distrust evolves at the system level. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change, and highlight the key role of network cluster dynamics in multi-species ecologies.
CoI: we are planning to do an anti-EBV vaccine study to prevent MS
