Tag: vaccine hesitancy

#MSCOVID19: cladribine is being unfairly tarnished with alemtuzumab’s brush

Barts-MS rose-tinted-odometer: ★★★★★

I think the North American MS community have made some mistakes with their COVID-19 vaccine recommendations, in particular, the NMSS COVID-19 vaccine guidelines for cladribine. In view of the immunology of cladribine’s mode of action and new data that is emerging, I would suggest the NMSS considers updating its guidelines. 

Lemtrada and Mavenclad

If you are about to start Lemtrada or Mavenclad, consider getting the Pfizer BioNTech or Moderna COVID-19 vaccine so that the second vaccine injection is done 4 weeks or more prior to starting Lemtrada or Mavenclad. If you are already taking Lemtrada or Mavenclad, consider administering the vaccine injections starting 12 weeks or more after the last Lemtrada or Mavenclad dose, with the optimal timing of the vaccine 24 weeks or more after the last DMT dose2. When possible, resume Lemtrada or Mavenclad 4 weeks or more following the second vaccine injection. This suggested scheduling is not always possible and getting the vaccine when it becomes available to you may be more important than timing the vaccine with your DMT. Work with your MS healthcare provider to determine the best schedule for you.

Lumping cladribine and alemtuzumab together as being immune-depleters of the same ilk is simply wrong. Alemtuzumab is more of a sledgehammer and is relatively non-selective in depleting both T-cells and B-cells and it also hits innate immunity, in particular monocytes. This is why there is a major infection signal (e.g. listeriosis) with alemtuzumab in the 4-6 weeks after each course of treatment. The latter does not occur with the doses of cladribine we use to treat people with MS.

In comparison, the mode of action of cladribine is very subtle and more in keeping with a selective B-cell depleting agent. Cladribine depletes B-cells by about 85-90% and hits mainly memory B-cells, in other words, large numbers of naive B-cell persist in the peripheral blood. We think as memory B-cells are being killed fresh naive B-cells are being released from the bone marrow. This is important because it is the naive B-cell population that is required to make new antibody responses to vaccines. 

Cladribine only depletes T-cells by about 50% a level that in general is not sufficient to put patients at risk of opportunistic infections or even viral infections. When we recently reanalysed all of the cladribine safety data there was no novel or new exogenous (from outside the body) viral infection signal. The only viral infection signal we saw was zoster or shingles, i.e. a reactivation of a latent virus, which is common and occurs with all immunosuppressive therapies. 

Another very big difference between cladribine and alemtuzumab is the fact that cladribine leaves the innate immune system intact, which is important for fighting infections and for processing vaccine antigens and presenting them to the immune system. 

Another factor that is different is the temporal profile of immunodepletion that occurs with alemtuzumab and cladribine. Alemtuzumab causes rapid cell lysis with its effect noticeable in hours to days; in other words, peripheral blood lymphocyte and monocyte counts are depleted to very low levels (nadir) very quickly. In comparison, cladribine works by triggering apoptosis of cells and lymphocytes die slowly over weeks to months reaching a nadir at about 3 to 4 months after each course. Therefore for the NMSS guidance to say “consider administering the vaccine injections starting 12 weeks or more after the last Mavenclad dose, with the optimal timing of the vaccine 24 weeks or more after the last DMT dose” is actually recommending giving the vaccine from the start of the nadir. 

Unlike alemtuzumab, I think the timing of vaccination in patients treated with cladribine is unlikely to make much of a difference because both the afferent (antigen processing and presentation) and efferent (B-cells/antibodies and T-cells) limbs of the immune system is intact, i.e. there is enough hardware or cells at all times post cladribine to make an immune response. Saying this the summary of product characteristics of cladribine clearly states that live vaccines should be avoided until the immune system has reconstituted and the cells counts have returned to normal. Please note this refers to live vaccines and doesn’t apply to the currently licensed COVID-19 vaccines, which are not live attenuated vaccines or LAVs.

The good news is that the above predictions are being borne out by some real-life flu and VZV vaccine data in cladribine-treated patients that have been presented at ACTRIMS this week. My interpretation of this data is that regardless of when a vaccine is administered in patients on cladribine the appear to mount a good antibody response. I agree the number of subjects studied is small and no subject has had grade 4 lymphopaenia (<200/mm3), but these data at least confirm what you would expect to happen based on immunological principles. 

My advice, therefore, remains the same for pwMS on DMTs; during the height of the pandemic having some immunity to SARS-CoV-2 is better than having no immunity. This is why you should get vaccinated ASAP. If you live in an environment where the background risk of COVID-19 is low then you may want to optimise the timing of your vaccine, when you are next dosed with an immunodepleting therapy or when you start or switch therapies.


Roy & Boschert. Analysis of Influenza and Varicella-Zoster Virus Vaccine Antibody Titers in Patients with Relapsing Multiple Sclerosis Treated with Cladribine Tablets. P059 – ACTRIMS 2021

Background: There is a lack of data available to determine the effect of cladribine tablets (CladT) on the antibody response to vaccination in patients with relapsing multiple sclerosis (MS).

Objectives: To investigate the immunoprotective response to seasonal influenza and varicella-zoster virus (VZV) vaccination in patients treated with CladT (3.5mg/kg over 2 years) for relapsing MS.

Methods: Blood samples collected during the MAGNIFY-MS study (NCT03364036) from 9 patients with relapsing MS treated with CladT who received seasonal influenza (n=8) or VZV vaccinations (n=1; Shingrix) as a standard of care were retrospectively analyzed. Two control blood samples (baseline sample before starting CladT and closest sample available just before vaccination) and two post-vaccination blood samples (closest sample available after vaccination) were examined. Quantitative antibody titers in response to the seasonal influenza and VZV vaccine were measured by hemagglutination inhibition (HAI) assay and Enzyme-Linked Immunosorbent Assay (ELISA), respectively. The seroprotection titer level for the seasonal influenza vaccine is considered ≥40, and was ≥100 IU/L for the VZV vaccine.

Results: Influenza: All patients vaccinated against influenza A and B during year 1 or 2 of CladT treatment retained seroprotection titers of ≥40 in post-vaccination samples across all strains present in the vaccine administered. The number of seropositive patients (HAI ≥40) with a ≥4-fold and ≥2-fold increase against at least 1 strain in post-vaccination titers were 3/8 and 7/8, respectively. VZV: Post-vaccination antibody titers were 40-fold increased over the protective titer at all time points (titers >4748 IU/L).

Conclusions: In this small retrospective investigation, post-vaccination antibody titers in patients treated with CladT for relapsing MS remained at levels that offer protective immunity against seasonal influenza and VZV.

Wu et al.  Evaluating the Impact of Cladribine Tablets on the Development of Antibody Titers: Interim Results from The CLOCK-MS Influenza Vaccine Substudy. P071 ACTRIMS 2021

Background: Cladribine tablets have been approved in more than 80 countries for the treatment of relapsing forms of multiple sclerosis (RMS), and are hypothesized to function as an immune reconstitution therapy with potential to cross the blood-brain barrier. The CLOCK-MS study (cladribine tablets: collaborative study to evaluate impact on central nervous system biomarkers in multiple sclerosis), is a 24-month, open-label, randomized, multicenter, collaborative Phase IV biomarker research study. The COVID-19 pandemic, and pending vaccine availability, have raised important questions around the impact of MS disease modifying therapies on vaccine efficacy.

Objectives: To evaluate the potential impact of prior treatment with cladribine tablets on the development of antibody titres post-influenza vaccination via a sub-study of CLOCK-MS.

Methods: The CLOCK-MS main study will enroll approximately 50 subjects age 18-65, diagnosed with relapsing-remitting MS or active secondary progressive MS, who had inadequate response to, or were unable to tolerate, an alternate drug indicated for the treatment of RMS. Study participants who have taken at least one dose of cladribine tablets and are planning to obtain one standard-of-care influenza vaccine are eligible to take part in the sub-study if they consent to blood draws. Blood sampling will occur 1) 3 Weeks Pre-Vaccine (within 21 days prior to obtaining a standard of care vaccine), 2) 4 Weeks Post-Vaccine (+/- 7 days), and 3) 6 Months Post-Vaccine (+/- 7 days). Measurements of antibody responses will be performed.

Results: So far 5 patients have been enrolled in this sub-study and had initial titers drawn. All patients fulfilled the per-label requirements for vaccination after cladribine tablets treatment. Initial results at Week 4 post-vaccination will be presented.

Conclusions: The impact of cladribine tablets, a lymphocyte-lowering agent, on the immune system’s ability to develop antibodies in response to a vaccine has not yet been studied. These results are expected to provide preliminary observations around the impact of cladribine tablets on influenza vaccine efficacy in patients with RMS.

CoI: multiple

Twitter: @gavinGiovannoni                                      Medium: @gavin_24211

#MSCOVID19: Vaccine Q&A page is now live

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

#MSCOVID19: Vaccine Decision Aid ver. 2.0

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

#MSCOVID19: What is vaccination?

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

#MSCOVID19: vaccine decision aid

Barts-MS rose-tinted-odometer: ★★★★★

Due to the number of emails and/or messages about the COVID-19 vaccines and MS I have been receiving I have put together a rough-and-ready decision aid to deal with the most common questions that have arisen so far.

Please note this is a beta version using Google Slide’s technology. As questions come in I will update the decision aid. If you think it is worthwhile we may be able to convert the decision aid into one of our ClinicSpeak web apps.

Your feedback on the design and format of the decision aid would be much appreciated. Thanks.

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

#MSCOVID19: from the horse’s mouth

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

Vaccine Hesitancy Survey

Thank you for completing our vaccine hesitancy survey. The results are self-explanatory and it is great to see that such a high proportion of you are prepared to have a COVID-19 vaccine.

We will be hosting a Barts-MS Question & Answer session on COVID-19 vaccines and our vaccination policy from 16h30-17h30, Tuesday 23rd February. We will be live-streaming the event via our YouTube channel. If you can’t watch the event live it will be recorded and remain available for asynchronous viewing at your leisure.

We have had plenty of question submitted already, but please feel free to complete the survey below, which will remain open. The survey allows yo to ask questions in the relevant open field at the end. Thank you.

CoI: multiple

We need you!

Barts-MS rose-tinted-odometer: ★★

Did you know that as of September 2020, only 54.1% of the public in the UK and 42.5% in the USA would ‘definitely’ accept a COVID-19 vaccine to protect themselves? 

I sincerely hope these figures are wrong and have changed substantially since September 2020. Why? These vaccine acceptance rates are lower than the proportion of vaccinated people required to achieve the anticipated herd immunity levels for SARS-CoV-2. Interestingly, in the study that produced these disturbing figures (see below), a higher proportion of individuals in both the UK and the USA would ‘definitely’ vaccinate to protect family, friends and at-risk groups, suggesting that effective altruistic messaging may be required to boost vaccine uptake. This is why I have always taken the line that vaccination is not necessarily about you, but society and in the case of COVID-19 vulnerable people. 

It is clear that misinformation/disinformation campaigns on social media have a remarkable effect on individual behaviour and lead to vaccine hesitancy. It is clear from recent political events across the globe that we need to move beyond the ‘post-truth era’ and reclaim the moral high ground and to start trusting our experts again. We have put in place institutions, such as our drug regulatory agencies, to protect the public. The fact that they have the necessary ‘deep expertise’ and have vetted and licensed several COVID-19 vaccines makes them safe to use at a population level. So my message is simple if you are offered a chance to be vaccinated with one of the COVID-19 vaccines take up the offer ASAP. The vaccine will not only protect you but your fellow citizens as well. In fact, you will be saving lives.  

The more unvaccinated people there are. particularly unvaccinated immunosuppressed individuals, the more opportunity the virus has to mutate and develop immune escape variants, i.e. new virus strains that are resistant to immunity from the current vaccines. These new strains will extend the pandemic, killed more people and make the economic impact of the pandemic worse. Based on this alone several commentators make the point that we all have a duty to be vaccinated.

What this study also shows that there is more to simply fighting the virus to end this pandemic; we have a propaganda war on our hands fighting both misinformation and disinformation about the safety and efficacy of COVID-19 vaccinations. I think we all have a responsibility to join this battle. Everyone needs to say something like  ‘I am a vaccinee and proud of it’ or ‘I have done my duty and have had the vaccine’. I am not a marketeer or advertising creative, but if you could come up with some catchy slogans we could then all push them out on social media and start a campaign. What do you think? 

Loomba et al. Measuring the impact of COVID-19 vaccine misinformation on vaccination intent in the UK and USA. Nature Human Behaviour (2021); published: 05 February 2021.

The widespread acceptance of a vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be the next major step in fighting the coronavirus disease 2019 (COVID-19) pandemic, but achieving high uptake will be a challenge and maybe impeded by online misinformation. To inform successful vaccination campaigns, we conducted a randomized controlled trial in the UK and the USA to quantify how exposure to online misinformation around COVID-19 vaccines affects the intent to vaccinate to protect oneself or others. Here we show that in both countries—as of September 2020—fewer people would ‘definitely’ take a vaccine than is likely required for herd immunity, and that, relative to factual information, recent misinformation induced a decline in the intent of 6.2 percentage points (95th percentile interval 3.9 to 8.5) in the UK and 6.4 percentage points (95th percentile interval 4.0 to 8.8) in the USA among those who stated that they would definitely accept a vaccine. We also find that some sociodemographic groups are differentially impacted by exposure to misinformation. Finally, we show that scientific-sounding misinformation is more strongly associated with declines in vaccination intent.

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

#MSCOVID19: misinformation vs. disinformation

Barts-MS rose-tinted-odometer: ★★

One of the reasons I started blogging was to counteract misinformation and eventually disinformation about CCSVI. CCSVI which started off as a hypothesis, supported by flawed and biased initial studies (misinformation) that was rapidly spread via social media channels, which then morphed into a disinformation campaign.

The CCSVI disinformation campaign included several conspiracy theories to explain the reluctance of neurologists to accept CSSVI as the cause of MS and to refer patients for so-called ‘liberation therapy’ procedures. The latter was soon followed by unscrupulous medical practitioners who opened up treatment centres to address the so-called unmet medical need for liberation therapy. The MS scientific and medical community were taken off guard but eventually responded and performed well-designed controlled trials to show that CCSVI was not a pathological entity and was not the cause of MS. Many of these studies demonstrated that liberation therapy was ineffective and probably caused more harm than good. Over time CCSVI has faded and is now rarely spoken about or searched for online (see Google trend metrics below). 

https://ssl.gstatic.com/trends_nrtr/2431_RC04/embed_loader.js trends.embed.renderExploreWidget(“TIMESERIES”, {“comparisonItem”:[{“keyword”:”CCSVI”,”geo”:””,”time”:”2008-01-01 2021-02-01″}],”category”:0,”property”:””}, {“exploreQuery”:”date=2008-01-01%202021-02-01&q=CCSVI”,”guestPath”:”https://trends.google.com:443/trends/embed/&#8221;});

The lessons learnt from CCSVI must not be forgotten, because the parallels between CCSVI and COVID-19 vaccine-hesitancy are remarkably similar, which is why we need to act. One way is for the medical and scientific community to get out there (1) to educate the community about vaccines and how they work, (2) to debunk the conspiracy theories about the COVID-19 vaccines, (3) make themselves available to the MS community to answer questions about the vaccines, (4) to be transparent with efficacy and safety data, (5) to admit that there are data gaps in relation to people with MS and (6) to set-up studies to answer questions and create an evidence base.

It is also important not to create a ‘them and us’ conflict. People who are hesitant about having a COVID-19 vaccine have valid personal reasons for not wanting to be vaccinated. We want to understand your reasons, discuss them and see if the science and data available is able to reassure you so that you may reconsider your position on vaccination.

We at Barts-MS are planning to host an online webinar or series of webinars to answer the many questions from you in response to the post on vaccine hesitancy. Rather than using email can you please complete the following short survey and leave your questions in the open field at the end. Thank you. 

If you are interested there is a great piece in this week’s BMJ on vaccine misinformation & disinformation. I suggest you read the article. 

Wardle & Singerman. Too little, too late: social media companies’ failure to tackle vaccine misinformation poses a real threat. BMJ 2021; 372.

Excerpts:

….. As the world looks to the new covid-19 vaccines with hope, there are major worries about how social media will affect uptake. 

….. The major social media companies are facing wide criticism for failing to deal with vaccine misinformation on their platforms.

…. Disinformation and misinformation are not the same things. When someone deliberately creates or shares false or misleading content, and they intend to cause harm, that’s disinformation. When they do so unwittingly and don’t intend harm, it’s misinformation. 

…. Before the covid-19 pandemic, social media companies had taken a hands-off approach, at least until 2016 when the Brexit referendum, along with elections in the Philippines and US, woke them up to political disinformation. And until recently they had done next to nothing to combat health misinformation. To experts, this oversight was especially worrying.

….. This laidback approach changed in 2018 when a series of measles outbreaks in the US seemed to be fuelled by vaccine misinformation. This was certainly not the first time that misinformation potentially affected a public health crisis, but because this took place in America, home of Facebook, Google, Twitter and others, it got the companies’ attention.

….. It’s only now, as pressure on the companies from governments, scientists, doctors, and the public hits breaking point, that they have changed their health misinformation policies all together. Facebook, Twitter, and YouTube all took a more assertive and expansive view of “harm.”

…. Despite this stronger stance, Facebook, Google, and Twitter are still uncomfortable accepting responsibility. They are not, they claim, “arbiters of truth,” merely middle men providing a platform to their users, the public. The companies fall back on directives from health organisations to determine what counts as false, misleading, or confusing, whether it’s international bodies like WHO or national bodies like the US Centers for Disease Control and Prevention and the NHS.

… . The decision to rely on expert organisations makes sense in principle, but in practice matters aren’t so simple. For one, scientific consensus struggles to keep pace with misinformation. Through the summer of 2020, health agencies flip flopped on guidance concerning masks and airborne transmission, while misinformation on these topics was allowed to fester.

… Unfortunately, you can’t just factcheck, label, or remove a narrative. They shape and sometimes dangerously warp how we make sense of the world. No matter how companies tackle these issues, their policies will come up short. On the one hand, even the most clearly written policies have flaws. Bad actors spreading disinformation will find loopholes, like those who posted websites that had been removed, by using new, seemingly harmless, links from the Internet.

…. As we enter 2021 and covid-19 vaccines are at last rolled out, misinformation is undoubtedly going to pose a serious barrier to uptake. The social media companies are at least showing a willingness to intervene. But people wishing to undermine trust in the vaccine won’t be using outright lies. Instead, they will be leading campaigns designed to undermine the institutions, companies, and people managing the rollout. They will be posting vaccine injury stories and providing first person videos detailing side effects that are difficult to factcheck. And, when well meaning local radio stations ask on Facebook, “Will you be getting the covid vaccine?” the comments will be flooded with conspiracy ideas and suggestions.

….. The question for the companies is whether they’re prepared to tackle this, even if such posts don’t break their current guidelines. This will sit uneasily with people who recognise that changing policies during a public health emergency could lead to a slippery slope that ends up curtailing freedom of speech. What’s required is more innovative, agile responses that go beyond the simple questions of whether to simply remove, demote, or label. We need responses that acknowledge the complexity of defining misinformation, of relying on scientific consensus, and of acknowledging the power of narratives. Unfortunately, we don’t have time to design them. So while we implore the social media companies to take a more active role, it is us, those who use social media, who need to start taking responsibility for our posting and sharing.

…. Let’s hope that, by the next pandemic, these challenges will have been tackled in ways that don’t leave us feeling as vulnerable to disinformation and misinformation as we do today.

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

#MSCOVID19: vaccine hesitancy

Barts-MS rose-tinted-odometer: ★★★

She is in her early thirties and is a first-generation ethnic minority immigrant to the UK. She was diagnosed as having MS 6 months ago after presenting with optic neuritis and a subsequent spinal cord syndrome. She is due to start on ocrelizumab in the next few weeks, but we want to delay her start until she has her first dose of one of the COVID-19 vaccines. However, she doesn’t want the COVID-19 vaccine. She is worried that it will ‘affect her DNA and any children she may have in the future’. I spent a lot of time explaining to her that what she has been told about the vaccine affecting her DNA is incorrect and simply not possible biologically and therefore the vaccine will not affect any children she has in the future. Fortunately, a 30-minute phone call to this particular patient seems to have worked. She has now agreed to take-up one of our early Barts-MS vaccination slots next week.

The above scenario represents just one of the conspiracy theories doing the rounds on social media concerning different COVID-19 vaccines. It is clearly incorrect. Similarly, there are many other conspiracy theories about the vaccines that also need to be dispelled. 

The survey below done quite early in the pandemic shows that in the USA only two-thirds of pwMS were willing to have a COVID-19 vaccine. This figure is over 90% in the UK but is highly variable globally. Just across the channel in France, a recent Ipsos survey showed that just over 40% of people said they would have a COVID-19 vaccine. A recent Lancet study (see below) highlights the variation in attitudes to vaccinations across the world.

In the US survey below vaccine willingness, is associated with education level, perceived risk for COVID-19 infection, and trust in COVID-19 information sources. 

Among less-educated communities trust, like knowledge, is built socially. People are more inclined to believe what their friends tell them, either in person or on social media. Clearly, the downside of this is that conspiracy and anti-science theories spread. However, this also provides us with an opportunity to build trust where it is lacking. What we need are local vaccine influencers from ethnic minorities and other communities to come forward to have the vaccine and spread the word that they are safe and that by having them you are not only protecting yourself but the wider community from getting severe COVID-19 and potentially dying from it.

COVID-19 vaccination is about public health, saving lives, protecting the NHS and getting society and the economy back to normal or let’s hope a more compassionate new normal. 

Scientists, pharma companies, regulators, governments and the NHS have delivered us effective, safe and accessible vaccines, which is the only realistic way out of this pandemic. It is now up to the population to take up the offer of having the vaccine. We in the UK are in a very privileged position when it comes to COVID-19 vaccinations; you only have to watch the shenanigans going on politically in terms of ‘vaccine nationalism’ to appreciate the significance of this. 

So if you want to become a local COVID-19 vaccination champion please contact us (bartsmsblog@gmail.com)  we can provide you with the necessary information to educate your friends and family. I and my colleagues are also prepared to set-up and run online meetings to answer any questions you may have about COVID-19 and the available vaccines. 

Please feel free to share any conspiracy theories about COVID-19 vaccines that you have heard about. The point is not to just dismiss them but to discuss them and hopefully convince people that they are not a good reason not to have the vaccine.

We are in this mess together and we need to get of this mess together and that means not leaving people behind and vulnerable to COVID-19.

Global trends in perceptions towards the safety of vaccines in November, 2015, and November, 2018 (Figure from the Lancet)

Ehde et al. Willingness to obtain COVID-19 vaccination in adults with multiple sclerosis in the United States. Mult Scler Relat Disord. 2021 Jan 22;49:102788. 

Background: As vaccines for the coronavirus become available, it will be important to know the rate of COVID-19 vaccine acceptability in adults with multiple sclerosis (MS), given that vaccination will be a key strategy for preventing SARS-CoV-2 infections. Using a national sample of adults with MS in the United States obtained early in the COVID-19 pandemic, the current study aimed to: (1) assess willingness to get a COVID-19 vaccine when available; (2) determine demographic, MS, and psychosocial correlates of vaccine willingness; and (3) measure where people with MS get their COVID-19 information and their perceived trustworthiness of such sources, which may influence COVID-19 vaccine willingness.

Methods: Adults with MS (N = 486) living in the United States completed a cross-sectional online survey (between 10 April 2020 and 06 May 2020) about their willingness to receive a COVID-19 vaccination once available. Participants also completed measures to describe the sample and to assess factors potentially related to vaccine willingness, including demographics, MS-specific variables, psychological measures, COVID-19 information sources, and perceived trustworthiness of their information sources.

Results: Approximately two-thirds of the participants (66.0%) reported a willingness to obtain a future COVID-19 vaccine, whereas 15.4%of the sample was unwilling. Greater willingness to receive the vaccine was associated with having a higher level of education and holding a higher perception of one’s risk of catching COVID-19. Participants reported accessing COVID-19 information from many different sources. Approximately a third (31.6%) of the sample reported getting their information from healthcare providers. Healthcare providers and the National MS Society had the highest perceived trustworthiness for COVID-19 information. The perceived trustworthiness of information sources was highly associated with vaccine willingness.

Conclusion: Early in the pandemic, willingness to get a COVID-19 vaccine was not universal in this large sample or people living with MS. Vaccine willingness was associated with a few variables including education level, perceived risk for COVID-19 infection, and trust in COVID-19 information sources. These results have important implications for guiding healthcare providers and the MS community as COVID-19 vaccines become widely available.

Figueiredo et al. Mapping global trends in vaccine confidence and investigating barriers to vaccine uptake: a large-scale retrospective temporal modelling study. Lancet. 2020 Sep 26;396(10255):898-908.

Background: There is growing evidence of vaccine delays or refusals due to a lack of trust in the importance, safety, or effectiveness of vaccines, alongside persisting access issues. Although immunisation coverage is reported administratively across the world, no similarly robust monitoring system exists for vaccine confidence. In this study, vaccine confidence was mapped across 149 countries between 2015 and 2019.

Methods: In this large-scale retrospective data-driven analysis, we examined global trends in vaccine confidence using data from 290 surveys done between September, 2015, and December, 2019, across 149 countries, and including 284 381 individuals. We used a Bayesian multinomial logit Gaussian process model to produce estimates of public perceptions towards the safety, importance, and effectiveness of vaccines. Associations between vaccine uptake and a large range of putative drivers of uptake, including vaccine confidence, socioeconomic status, and sources of trust, were determined using univariate Bayesian logistic regressions. Gibbs sampling was used for Bayesian model inference, with 95% Bayesian highest posterior density intervals used to capture uncertainty.

Findings: Between November, 2015, and December, 2019, we estimate that confidence in the importance, safety, and effectiveness of vaccines fell in Afghanistan, Indonesia, Pakistan, the Philippines, and South Korea. We found significant increases in respondents strongly disagreeing that vaccines are safe between 2015 and 2019 in six countries: Afghanistan, Azerbaijan, Indonesia, Nigeria, Pakistan, and Serbia. We find signs that confidence has improved between 2018 and 2019 in some EU member states, including Finland, France, Ireland, and Italy, with recent losses detected in Poland. Confidence in the importance of vaccines (rather than in their safety or effectiveness) had the strongest univariate association with vaccine uptake compared with other determinants considered. When a link was found between individuals’ religious beliefs and uptake, findings indicated that minority religious groups tended to have lower probabilities of uptake.

Interpretation: To our knowledge, this is the largest study of global vaccine confidence to date, allowing for cross-country comparisons and changes over time. Our findings highlight the importance of regular monitoring to detect emerging trends to prompt interventions to build and sustain vaccine confidence.

CoI: multiple

Twitter: @gavinGiovannoni                               Medium: @gavin_24211

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