Prof G's MS Blog Archive

#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

On being EBV-negative and having MS

Barts-MS rose-tinted-odometer: ★★★★★

I have been diagnosed with MS and I am Epstein Barr Virus (EBV) negative. Therefore, EBV is not the cause of MS. Correct? I wish it was that simple.

Firstly, no laboratory test is 100% sensitive and specific. In other words, some people who have negative standard EBV serology may still have the virus, i.e. a false negative result, and some people who have a positive result may not have the virus a so-called false-positive result. A very sensitive assay is one that limits the number of false-negative results, i.e. gets the result correct almost all the time. A very specific assay limits the number of false-positive results and excludes those with infection or disease. Do these terms give you a sense of deja vu? The COVID-19 lab tests have made them part of the public lexicon.

In this study below we checked out two commercial EBV serology assays and as expected they were not perfect. So yes you can be EBV-antibody negative and still have EBV.

Dobson et al. Comparison of two commercial ELISA systems for evaluating anti-EBNA1 IgG titers. J Med Virol. 2013 Jan;85(1):128-31.

High IgG titers against the Epstein-Barr virus nuclear antigen, EBNA-1, have been strongly correlated with the risk of developing multiple sclerosis. ELISAs are used frequently to measure EBNA-1 titers, however concerns remain regarding the accuracy of results. Ordering absolute results into rank quintiles for analysis may be preferable. Using 120 serum samples, two commercially available ELISAs (produced by DiaSorin and VirionSerion) were compared, both in terms of absolute results and rank quintiles. The positive predictive value of the VirionSerion ELISA was 99.1% when compared to the DiaSorin ELISA, however, the negative predictive value was 64.3%. Sensitivity and specificity were acceptable at 95.5% and 90.0%, respectively. There was poor correlation between absolute results, R(2) = 0.49; and the kappa coefficient for rank quintiles was low at 0.23. Although sensitivity and specificity appear adequate, the poor negative predictive value and kappa coefficient are of major concern. Care must be taken when selecting assays for experimental use.

In a meta-analysis of EBV and MS, we showed that when you use the immunofluorescence assay, which although being very labour intensive is considered the gold standard for diagnosing MS 100% of pwMS were EBV-positive. Interesting? Then on the flip side being EBV immunofluorescence negative was the most powerful predictor of not getting MS. These and other findings are part of the evidence that convinced me decades ago that EBV is the cause of MS.

Pakpoor et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler. 2013 Feb;19(2):162-6.

Background: Epstein-Barr virus (EBV) infection is widely considered to be a risk factor for multiple sclerosis (MS). A previous meta-analysis estimated an odds ratio (OR) for MS in individuals seronegative for EBV of 0.06. Given the potential importance of this finding, we aimed to establish a more precise OR for adult and paediatric onset MS in EBV seronegative individuals.

Methods: PubMed and EMBASE searches were undertaken to identify studies investigating the association between MS and EBV. Twenty-two adult and three paediatric studies were included. ORs were calculated using a fixed effects model. A sub-group analysis based on the method of EBV detection was performed.

Results: The OR for developing adult MS in EBV seronegatives was 0.18 (95% confidence interval (CI) 0.13-0.26)) and for paediatric MS was 0.18 (95% CI 0.11-0.30). Sub-group analysis on EBV detection method showed that studies which used immunofluoresence generated an OR=0.07 (95% CI 0.03-0.16); for those that used enzyme-linked immunosorbent assay (ELISA) OR=0.33 (95% CI 0.22-0.50) and for studies which used ELISA and immunofluoresence OR=0.00 (95% CI 0-0.43).

Conclusion: The sensitivity and specificity of the assay used to measure EBV antibody titres have an influence on the association between MS and EBV. Looking at studies where two independent methods are used and therefore are likely to be the most robust, EBV appears to be present in 100% of MS patients. This has implications for future studies of EBV in MS. MS patients without EBV infection, if they truly exist, should be studied in more detail.

Now, what about the diagnosis of MS?

In the study below approximately 1 in 5 people diagnosed with MS don’t have MS. This figure is much higher than in previous studies. I usually quote a large Danish post-mortem study that suggests only 1 in 20 people with MS (pwMS) are misdiagnosed. It is important to realise that there is no one test that can be done to diagnose MS. MS is diagnosed by combining a set of clinical and MRI findings, electric or neurophysiological investigations and laboratory tests. If these tests fulfil a set of so-called MS diagnostic criteria the Healthcare professional (HCP) or neurologist makes a diagnosis of MS.

The underlying principle of making a diagnosis of MS is showing dissemination of lesions in space and time and excluding other possible diagnoses that can mimic MS. The diagnostic criteria have evolved over time from being based purely on clinical finding to the more recent criteria that include evoked potentials, spinal fluid analysis and MRI to help confirm dissemination in time and space.

Dissemination in time means two attacks or MS lesions occurring at least 30 days apart. Dissemination in space means lesions occurring in different locations, for example, the optic nerve and spinal cord.

The electrical or neurophysiological tests are called evoked potential (EPs) and test electrical conduction in a particular neuronal pathway. They can be useful to show the effects of lesions in pathways that are not evident on neurological examination or seen on MRI. The EPs can also show slow electrical conduction which is one of the hallmarks of diseases that affect myelin, the insulation of nerves that are responsible for speeding up electrical conduction.

The laboratory tests are typically done to exclude other diseases that can mimic MS. One test that is useful in helping to make the diagnosis of MS is examining the spinal fluid for the presence of oligoclonal immunoglobulin G or IgG bands (OCBs), which are the fingerprint of a specific type of immune activation within the central nervous system (CNS).

The OCB fingerprint is relatively specific for the diagnosis of MS in the correct clinical context. Please note OCBs can are found in infections of the nervous system and other autoimmune diseases, therefore, the presence of OCBs are not diagnostic on their own.

Please note being EBV seropositive is currently not part of the diagnosis of MS so you can be diagnosed with MS and still be EBV-negative. What we don’t know is whether or not EBV-negative MS is biological MS, i.e. the same disease as EBV-positive MS. This is something I have been wanting to study for a long time.

I have spent some time explaining this all to you as we neurologists get the diagnosis wrong approximately 5% of the time and if this paper below is correct maybe in even a higher number of patients. In other words, at least 1 in 20 people who have a diagnosis of MS in life don’t have MS when their brains are studied at postmortem.

Why is getting the correct diagnosis of MS so important? Firstly, some of the treatments for MS have life-threatening complications; you don’t want to expose people without MS to these complications. Some diseases that mimic MS can be made worse by MS DMTs. This latter is particularly relevant for NMO or neuromyelitis optic. Patients with NMO misdiagnosed as having MS get worse on many of the MS DMTs. Finally, a diagnosis of MS has many psychological, social, financial and economic implications for people. Just having a diagnosis of MS, even if you turn out to have benign MS in the future, has implications for the person concerned. For example, it may affect your life choices and may impact your ability to get insurance cover to name to obvious examples. I would, therefore, advise you to make sure you have MS and not an MS mimic.

The most common MS mimics:

The evolving definition of MS based on diagnostic criteria:

Clinical criteria only:

Schumacher, et al. Problems of Experimental Trials of Therapy in Multiple Sclerosis: Report by the Panel on the Evaluation of Experimental Trials of Therapy in Multiple Sclerosis. Ann N Y Acad Sci 1965;122:552-68.

Clinical, EPs and CSF analysis:

Poser, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-31.

Clinical, EPs, CSF analysis and MRI:

What the evolving definition of MS tells us is that the diagnosis and hence the disease MS as we currently define it is a moving target. In other words, someone 10 years ago who do not fulfil the diagnosis of MS, i.e. didn’t have the disease, maybe diagnosed today as having MS. How can this be? This is why I would prefer to use a biological definition of MS. Yes, I am currently working on a paper that sets out the principles for redefining MS as a biological disease.

So what then do I do at the moment if I have MS and I am EBV negative? Until we prove EBV is the cause of MS and include EBV in the diagnosis I don’t think knowing if you are EBV positive or negative makes any difference to the diagnosis of MS and its management.

However, I would like to challenge the status quo. Can we really continue to ignore the evidence linking EBV to MS? Don’t we owe it the next generation of pwMS to act on this information ASAP? Is anyone prepared to donate several million dollars to a consortium to EBV treatment and prevention trials in MS, i.e. the Charcot Project?

Kaisey et al. Incidence of multiple sclerosis misdiagnosis in referrals to two academic centers. Mult Scler Relat Disord. 2019 May;30:51-56.

BACKGROUND: Multiple Sclerosis (MS) specialists routinely evaluate misdiagnosed patients, or patients incorrectly assigned a diagnosis of MS. Misdiagnosis has significant implications for patient morbidity and healthcare costs, yet its contemporary incidence is unknown. We examined the incidence of MS misdiagnosis in new patients referred to two academic MS referral centers, their most common alternate diagnoses, and factors associated with misdiagnosis.

METHODS: Demographic data, comorbidities, neurological examination findings, radiographic and laboratory results, a determination of 2010 McDonald Criteria fulfillment, and final diagnoses were collected from all new patient evaluations completed at the Cedars-Sinai Medical Center and the University of California, Los Angeles MS clinics over twelve months.

RESULTS: Of the 241 new patients referred with an established diagnosis of MS, 17% at Cedars-Sinai and 19% at UCLA were identified as having been misdiagnosed. The most common alternative diagnoses were migraine (16%), radiologically isolated syndrome (9%), spondylopathy (7%), and neuropathy (7%). Clinical syndromes and radiographic findings atypical for MS were both associated with misdiagnosis. The misdiagnosed group received approximately 110 patient-years of unnecessary MS disease-modifying therapy.

CONCLUSION: MS misdiagnosis is common; in our combined cohort, almost 1 in 5 patients who carried an established diagnosis of MS did not fulfill contemporary McDonald Criteria and had a more likely alternate diagnosis.

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Eight Swallows

Barts-MS rose-tinted-odometer: ★★★★★

How many swallows make a summer? Is eight enough?

If MS is caused by EBV you would expect there to be clusters of MS potentially linked to a specific subtype of the virus. The best-studied MS cluster is the one from Fjelsø, a small village of 74 families in rural Denmark, where eight people closely linked to each other all developed MS within 13 years of each other. All the subjects had attended the same school. Interestingly all of the people who developed MS had attended the scouts together.

Danish investigators then typed the variant of EBV these subjects had been infected with and to their surprise, they all had the same subtype of EBV, which importantly was different from controls that were selected from schoolmates and family members. This raises the question of being a scout in Denmark resulted in the transmission of EBV between these subjects. None of these eight subjects reported having had infectious mononucleosis.

What are the chances of getting an eight-person cluster of MS from a group of scouts in a tiny rural village in Denmark? Then on top of this what are the chances of all eight of these people with MS having the same EBV subtype when their family members and schoolmates did not? I suspect the chances are very low.

I don’t think eight swallows are enough to make a summer, but you can’t ignore this cluster when all the other epidemiological evidence points to EBV being causally linked to MS.

The two linked studies below are just a small piece of a large jigsaw puzzle that is gradually being built that I predict will eventually prove EBV is the cause of MS. In the centre of this large jigsaw puzzle are the bespoke pieces for the EBV antiviral and vaccine studies.

Haahr et al. Cluster of multiple sclerosis patients from Danish community. Lancet. 1997 Mar 29;349(9056):923.

Cluster: We report a cluster of MS in which eight people with verified MS originated from a small Danish community called Fjelsø. All eight had lived within a 2.75 km2 area (2.5 km×1.1 km), where 74 single-family houses, including some farms, were located. The community had a stable population with few migrations into and out of the area. During a 13-year period, all the patients had for 7 years attended the same elementary school with 70-80 pupils. The school had 145 pupils during this period. All those who developed MS had been scouts together, with the older ones being scoutmasters for the younger ones and some of the older ones had also looked after the younger ones. Two cases were siblings and two were aunt and nephew, but MS had not been observed in any of the ancestors of the eight cases or among the school teachers. All cases of MS developed, at various ages and with variable courses, after the eight had left Fjelsø. None of the eight could recall symptoms of infectious mononucleosis.

Munch et al. A single subtype of Epstein-Barr virus in members of multiple sclerosis clusters. Acta Neurol Scand. 1998 Dec;98(6):395-9.

Objectives: Epidemiological studies strongly indicate an infectious involvement in multiple sclerosis (MS). Epstein-Barr virus (EBV), to which all multiple sclerosis patients are seropositive, is also interesting from an epidemiological point of view. We have reported a cluster of MS patients with 8 members from a small Danish community called Fjelsø. To further evaluate the role of EBV in MS we have investigated the distribution of EBV subtypes in cluster members and in control cohorts.

Materials and methods: Blood mononuclear cells were isolated from cluster members, unrelated MS patients, healthy controls, including healthy schoolmates to the Fjelsø cluster patients and finally from persons with autoimmune diseases in order to investigate the number of 39 bp repeats in the EBNA 6-coding region in the EBV seropositive individuals.

Results: We observed a preponderance of the subtype with 3 39 bp repeats in the EBNA 6-coding region both in the MS patients and the healthy controls. In the Fjelsø cluster, all 8 cluster members were harbouring this subtype, which is significantly different from the finding in healthy controls (n = 16), which include 8 schoolmates to the cluster members and 8 randomly selected healthy persons (Fischer’s exact test P = 0.0047), and also compared to all non-clustered individuals studied (P = 0.017).

Conclusion: Infection with the same subtype of EBV links together the 8 persons from the Fjelsø cluster who later developed MS. This finding adds to the possibility that the development of MS is linked to infection with EBV.

CoI: multiple

Twitter: @gavinGiovannoni Medium: @gavin_24211

Prof G’s final update

Barts-MS rose-tinted-odometer: ★★★★★

Despite posting an update on my progress just a few weeks ago I am still getting daily texts, emails and social media messages about how my rehab is going. So here is my final update.

Once you are over the initial 4-6 weeks after polytrauma things, at least in terms of improvement, slow down a lot. So not much has actually changed in the last three weeks since my last update on the 22nd of January.

I was clearly overdoing it and yes I admit you told me so. When I had an x-ray of my pelvis a few weeks ago the fracture of my left superior pubic ramus was not healing. Probably because I was doing too much exercise, which was causing some movement at the fracture site and non-union. I have been advised not to do anything that makes the pelvic pain worse.

I weaned my anti-inflammatories only to find that were masking a lot of my pelvic pain. As a result, I have dramatically cut down on my walking, stopped using the exercise bike for cardio work-outs and I am limiting my lower limb exercises to those that aren’t painful.

Things were going well until I volunteered to be a pallbearer at our friends funeral on Monday; the additional weight-bearing strain on my fragile pelvis has made my pelvic pain a lot worse. So much so that I had to restart my anti-inflammatory medication this week.

The good news is that I am continuing to notice and improvement in the range of movement in my right or injured hip. I still have limitations with hip flexion and internal and external rotation of the hip. Any rapid movements in the hip, particularly flexion when the hip is externally rotated, is very painful. I have worked out that this likely to be due to activation and contraction of the pectineus muscle that is attached to the superior pelvic ramus where my fracture is. Could this be one of the muscles that are causing my fracture line to move ever so slightly and delaying it from healing? As a result of the pain, I now walk with a noticeable, albeit a slight, limp. In neurology jargon, we call this an antalgic gait.

My major concern is whether or not I will be able to run again. I was told by my orthopaedic surgeon not to attempt running for at least 6 months, which will take me to May. I really can’t imagine a life without running, but who am I to complain when so many of my patients with MS have had to resign themselves to never being able to run or even walk again. I think I am beginning to understand the mental toll MS places on people when they realise their physical and mental disabilities are worsening.

During the accident, I had a hyperextension injury of my left ring and middle fingers. This injury is now causing me a lot of trouble with swelling of the interphalangeal joints of both these fingers and the beginning of hyperextension-flexion contractures in these figures. I suspect the latter is due to an imbalance in power between my forearm muscles and the intrinsic muscle of my left hand. Yes, I still have mild weakness in my C7 and C8 innervated muscles of the left arm. The imbalance on power causing clawing of the fingers is a common mechanism that afflicts many people with peripheral nerve problems. The good news is that my muscle strength is returning slowly, particularly around my shoulder and scapular, for example, the winging of my scapular has almost resolved. I hope my finger deformities improve as well.

The most recent CT scan of my cervical spine shows my vertebral fractures are healing well. I am not using a neck brace, but still have stiffness and pain in my neck, particularly when I move it quickly. My stamina in terms of sitting and standing is improving and I can now manage about 6 hours before needing to rest my neck muscles. I have reclining chairs with headrests in both my offices at work and at home. Another reminder that you need to have resources, essentially money, to ensure you can return to work with equipment that allows you to function without too much pain.

I am now back at work doing remote clinics, catching-up on teaching tasks and generally doing what I used to do, however, all at a much slower pace. My physiotherapist has adapted my exercise programme so that I can do most of my exercises, at least my upper body exercises, in my office during the day and has truncated the programme to make it less time-consuming. I am still sticking to the programme in the hope I will get back to normal.

My attention and concentration are still relatively poor. I am having problems tackling big creative writing tasks. As a result, I am not nearly as productive as I should be. However, things are improving and I feel that by being back in my office, without distractions, I am achieving a little more each day. Yes, I am back doing endless zoom calls.

Overall my attitude remains positive; I still feel lucky to be alive without a major disability. I also realise how privileged I am to be able to afford private rehabilitation and to be able to purchase the necessary equipment for my rehabilitation. As ever I am grateful for living in a country where universal healthcare is a basic human right. The NHS is such an extraordinary institution, which most of us take for granted. I would urge you not to take it for granted; you only have to look around the world to understand why the NHS and its staff need attention and care.

Finally, can I please make this the last update for the next three or four months? As far as my clinical and academic activities go I am back working full-time and want to be treated as such. You will find me saying no to a lot of things mainly because I have reset my priorities. If I ever do another update it will be when I am back running again, or not.

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

Virtual MS Trust Conference 2021

If you are a jobbing MS Health Care Professional, i.e. on the coalface of MS care, then the annual MS Trust conference is the place to be. The range of topics, talks and issues that will be discussed in a pragmatic and clinically relevant way make this the one meeting to attend this year (28th Feb to 2nd March 2021). Please click on the link to register.

Due to COVID-19, the 2020 meeting was cancelled and this year’s meeting is going online. This will allow you to attend from the comfort of your office or home and will allow you to dip into the content remotely in your own time.

Click here to register!

CoI: I am biased as I am talking at the meeting. I have always felt the MS Trust Annual Conference, which is the only UK conference dedicated entirely to MS and its management, that all MS HCPs should attend. Sadly, too few neurologists do; if neurologists did attend I think MS services in the UK would be in a much better place.

What is the most exciting MS research on the horizon?

I was asked about which paper I have written or co-written that has or will have the most impact in the field of MS. There is little doubt that it is our report of our 2017 workshop on “EBV Infection and MS Prevention”.

This report (see below) was the catalyst for creating the Preventive Neurology Unit (PNU), which is embedded in the Wolfson Institute of Preventive Medicine. The funding for the PNU allowed us to employ Dr Ruth Dobson to be the academic lead on the MS Prevention workstream in the PNU. All we need now is a sterilising vaccine against EBV, the necessary funding so that we can set-up an international anti-EBV MS Prevention study and support from the public to do this study. Once we have all these in place we will be a position to finally test the hypothesis that EBV is the cause of MS. There is nothing in the field of MS research that excites me more than testing this hypothesis. Do agree? What excites you? Any other recommendations?

CoI: multiple

#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/”});

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