Please, please, please #GetVaccinatedASAP

Barts-MS rose-tinted-odometer: ★ (Black & White Friday)

As the delta variant of SARS-CoV-2 is surging it is putting residents of Whitechapel at serious risk of getting COVID-19.

This is important because the vaccination rate in Whitechapel is so low; less than 30% of adults have both dose of the COVID-19 vaccine.

Why is the uptake of vaccines so low in our local community?

Vaccine hesitancy is very high in Whitechapel and the reason are complex. If you can do anything to encourage people to get vaccinated please do. We in Barts Health NHS Trust and the Royal London Hospital are bracing ourselves for another surge of COVID-19 admissions, but the knock-on effects on other services, including our MS service, will take its toll on staff and people with MS.

The following are a some answers to questions that vaccine hesitators may ask. if you are a hesitator are there any questions I have missed out?

The following Questions and Answers have been adapted from the Quinn &  Andrasik perspective in this week’s NEJM.

How did these trials move so quickly?

Researchers used existing clinical trial networks.
Manufacturing started while the clinical trials were still underway.
Adenoviral and mRNA vaccines are faster to produce than traditional vaccines.
Other sponsors use platforms that have proven successful in the development of vaccines.
The studies included more participants than a typical study and disease transmission rates were high, enabling researchers to determine efficacy in a short time.
The MHRA prioritized review, authorization, and recommendation of Covid-19 vaccines.

Were vaccines tested on people like me?

Yes.
Vaccine trials included all adults >18 yr of age.
It was mandated that a large number (~20-25%) of participants in most trials had to be >65 yr of age.
Study participants included ~25% of people with common health problems such as high blood pressure, diabetes, HIV, and cancer.
There were no exclusions for diseases or medications, except immunosuppression.
Vaccine studies did not include pregnant people.

Do these vaccines work for all races/ethnic groups?

Yes. There is strong evidence that the vaccines work well for all people, regardless of their genetic background.
What types of reactions have been reported after vaccination?
Common reactions: Sore arm, headache, aches, fever may appear within 48 hours. These are similar to reactions seen after shingles and influenza vaccines.
Rare reaction: anaphylaxis, blood clots
Current recommendation: 15 minutes of observation after injection
If you have a history of severe allergies or an anaphylactic reaction to a vaccine, it’s recommended that you discuss vaccination with your provider and undergo 30 minutes of observation after receiving the vaccine.
Most people with a history of allergies or anaphylaxis have received a vaccine with no issues.

Should I get a vaccine now or “wait and see”?

You should be vaccinated as soon as possible.
You are not the first:  Over 1 billion people have received COVID-19 vaccines
Immunity takes time to develop and you are only maximally covered against the new variants of the virus about 2 weeks after your second or booster dose of the vaccine. 
Please note the new Covid-19 strains are more contagious and cause more severe disease than the old variants.

Does mRNA and adenovirus DNA change your DNA?

No; mRNA and  adenoviral DNA is a signal to your cell. It stays in the outer part of the cell and does not enter the nucleus where your nuclear DNA is located.
The mRNA and adenoviral DNA in the vaccine is present in the body for only 1–3 days; then it degrades and the immune system is primed and ready.

I’ve heard that the vaccines ….?

No, it will not give you Covid-19.
No, it does not affect women’s fertility.
No, it does not contain fetal tissue, microchips, or any other devices.

Which vaccine is the best?

All the vaccines are very good at preventing severe disease, so they will greatly reduce rates of severe disease progression, hospitalization, and death. When you are offered a vaccine, you should take it. Because the adenoviral vaccines are associated with rare blood clots, which is mainly in younger people (<30), it is recommended that young people have the mRNA vaccines (Pfizer or Moderna). 

Why do I have to wear a mask after getting immunized against Covid-19?

The vaccines prevent Covid-19 disease, severe disease, and death.
We know much less about whether vaccines prevent asymptomatic infection, as this question was not studied. Until we know that, we must assume that vaccinated people might get Covid-19 and not know it.
Masks, social distancing  and handwashing are still required until we have more information.

Is one dose of  vaccine as effective as two doses?

The data are very clear that the best protection from Covid-19 disease happens after the second (booster) dose.
The first dose starts the immune response, and the second dose boosts it to make high antibody levels.

How long does vaccine immunity to Covid-19 last?

We don’t know. Covid-19 is a brand-new human disease, and we will need more time to determine how long vaccine responses last.

How will viral mutations affect Covid-19 vaccines?

Current vaccines work well against the variant originally identified in the UK.
There seems to be some reduced efficacy for the variants originally identified in South Africa, Brazil and India. 
The vaccines are still highly effective in preventing severe disease (reducing risk of being hospitalised, requiring supplemental oxygen, needing a ventilator) and death.
The vaccines may not prevent you from getting mild symptoms, but they will prevent severe disease.

Please get out there and become a pro-vaccine warrior. The sooner we flatten the tail of this pandemic with vaccine immunity and not herd immunity form wild-type infection the lower the risk of immune escape variants and the fewer deaths.

Quinn &  Andrasik. Addressing Vaccine Hesitancy in BIPOC Communities — Toward Trustworthiness, Partnership, and Reciprocity. N Engl J Med 2021; 385:97-100. 

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice. 

73 tomorrow – some achievement

Barts-MS rose-tinted-odometer: ★★★★★ (Today’s colours are NHS blue & yellow #005EB8 & #FAE100)

Tomorrow the NHS turns 73. If you love the NHS and want to give it and its staff a present please have your COVID-19 vaccine. Barts Health NHS Trust and many other NHS services are running walk-in vaccine centres.

https://platform.twitter.com/widgets.js

We are now in the long tail of this pandemic and the sooner we all get vaccinated the sooner the curve will flatten and the tail will get shorter.

Thank you.  

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.

#MSCOVID19: get vaccinated

Barts-MS rose-tinted-odometer: ★ (Blue Thursday #000080)

Where are all the new MS patients gone? We have national data showing that there has been a 30% fall in the number of new patients with MS starting on disease-modifying therapies (DMTs) during the COVID-19 pandemic. Where are these patients? I suspect due to the reconfiguration of the NHS because of COVID-19 many of these patients have yet to find their way through the diagnostic pathway. 

Many patients may have had neurological symptoms suggestive of a demyelinating syndrome and decided against seeking medical attention during the crisis. As these symptoms may have remitted they have now gotten on with their lives. Others are waiting for MRI scans, lumbar punctures and evoked potentials. 

We were hoping our Barts-MS service would get back to some form of new normal, but this is unlikely to happen for some time. A big concern is a recent increase in COVID-19 cases as a result of the Delta or Indian variant of SARS-CoV-2. More worrying is the low rate of vaccine uptake in our local area due to vaccine hesitancy

As you can see from the latest Government figures infections rates in Whitechapel are surging well above the national average and the vaccine data figures are very worrying; the majority of adults in Whitechapel have not been vaccinated and more importantly, less than a quarter (24.3%) have not had two doses compared to close to 60% nationally. At the Royal London Hospital, we are therefore bracing ourselves for a third/fourth wave of admissions. This will have knock-on effects and affect routine hospital services such as our Barts-MS service. The best thing you can do as an individual is to #GetVaccinatedASAP to prevent hospital admissions and deaths and to allow the NHS to get routine services back to normal. 

I have little doubt based on the principle that ‘time is brain’ that many people yet to be diagnosed with MS will do worse because of the inevitable delays in the management of their MS.

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#MSCOVID19 – the fourth wave

Barts-MS rose-tinted-odometer: ★★★ (a blueish-green Thursday; looking forward to being a weekend warrior  #0d98ba )

My heart sank when I saw the latest COVID-19 UK case numbers. Here we go again? I don’t think so simply because the vaccines are working as well as the protective immunity induced by wild-type SARS-CoV-2 infection. I just wish the Government would take a pragmatic approach to the science and allow people who have been vaccinated (double-dose) and with confirmed previous SARS-CoV-2 infection to get back to normal. 

It is clear from Israel that people who have had COVID-19 are as immune as vaccinated people to (re)infection with the virus. This will almost certainly apply to the circulating variants that as yet are not immune escape variants, i.e. capable of reinfecting large numbers of people who are meant to be immune to SARS-CoV-2. 

The biggest concern with the current Indian or Delta SARS-CoV-2 variant is that it is more transmissible and more virulent, which means people who are not vaccinated are taking a big risk. This is very relevant to the East end of London where the vaccination rates in adults are below 50% because of significant vaccine hesitancy in the local population. We are therefore at high risk of a significant fourth wave of infections, which will have implications for our hospital and other services, including the MS service. We really need some respite from fighting and dealing with COVID-19 so that we can get back to normal or at least near normal. So please think carefully about resisting vaccination; you are not only putting yourself at risk but are impacting the health of others.

Please remember that COVID-19 and SARS-CoV-2 are going nowhere soon and will almost certainly become endemic, i.e. the virus and its variants will remain with us forever. So if you have not been vaccinated you will at some point in time get exposed to SARS-CoV-2 and get COVID-19. The risks of COVID-19 and its consequences, including long-COVID, are orders of magnitude worse than the risks of the vaccine. Therefore please #GetVaccinatedASAP. In my opinion there really are very few reasons to say no! Do you agree?

Goldberg et al. Protection of previous SARS-CoV-2 infection is similar to that of BNT162b2 vaccine protection: A three-month nationwide experience from Israel.  medRxiv preprint doi: https://doi.org/10.1101/2021.04.20.21255670.

Worldwide shortage of vaccination against SARS-CoV-2 infection while the pandemic is still uncontrolled leads many states to the dilemma whether or not to vaccinate previously infected persons. Understanding the level of protection of previous infection compared to that of vaccination is critical for policy making. We analyze an updated individual-level database of the entire population of Israel to assess the protection efficacy of both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with COVID-19, severe disease, and death due to COVID-19. Vaccination was highly effective with overall estimated efficacy for documented infection of 92·8% (CI:[92·6, 93·0]); hospitalization 94·2% (CI:[93·6, 94·7]); severe illness 94·4% (CI:[93·6, 95·0]); and death 93·7% (CI:[92·5, 94·7]). Similarly, the overall estimated level of protection from prior SARS-CoV-2 infection for documented infection is 94·8% (CI:[94·4, 95·1]); hospitalization 94·1% (CI:[91·9, 95·7]); and severe illness 96·4% (CI:[92·5, 98·3]). Our results question the need to vaccinate previously-infected individuals.

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Long-COVID

Barts-MS rose-tinted-odometer: ★★

If anyone who has any doubts on the debate of getting or not getting COVID-19 and taking your chances without being vaccinated needs to read the paper below in this week’s BMJ on long-COVID.

Long-COVID is a serious problem and should not be dismissed as something minor. Long-COVID is not simply post-viral fatigue. So if you are one of those people who is nervous about having the vaccine I would urge you to think again. There is no doubt in my mind getting COVID-19 is much worse and riskier than having any of the licensed COVID-19 vaccines. If you don’t have the vaccine you have to assume that at some point in the future you will get COVID-19; this virus is not going away it will become endemic.

So my message remains simple #StayCalm #BeRational #GetVaccinatedASAP

Figure from BMJ

Ayoubkhani et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ 2021;372:n693

Objective: To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.

Design: Retrospective cohort study.

Setting: NHS hospitals in England.

Participants: 47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records.

Main outcome measures: Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020. Variations in rate ratios by age, sex, and ethnicity.

Results: Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of respiratory disease (P<0.001), diabetes (P<0.001), and cardiovascular disease (P<0.001) were also significantly raised in patients with covid-19, with 770 (95% confidence interval 758 to 783), 127 (122 to 132), and 126 (121 to 131) diagnoses per 1000 person years, respectively. Rate ratios were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease (10.5 (95% confidence interval 9.7 to 11.4) for age less than 70 years v 4.6 (4.3 to 4.8) for age ≥70, and 11.4 (9.8 to 13.3) for non-white v 5.2 (5.0 to 5.5) for white individuals).

Conclusions: Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population. The increase in risk was not confined to the elderly and was not uniform across ethnicities. The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.

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COVID-19 vaccine thrombosis update

Barts-MS rose-tinted-odometer: ★★

Last week I heard from an Italian colleague that in Italy when many people arrive for the COVID-19 vaccine slot and find out that the vaccine on offer is the Oxford-AstraZenca (AZ) vaccine they say no thank you and leave. The main reason they give for turning down the AZ vaccine is the thrombosis risk. I wonder if these people are aware of the new data that emerged last week (see below). 

In this big data study from the US, the incidence of cerebral venous thrombosis (CVT) after COVID-19 diagnosis was 39.0 cases per million people who get COVID-19. This was higher than the CVT incidence after influenza (0.0 per million people or adjusted relative risk = 6.7) or after receiving the Pfizer-BionTech or Moderna RNA vaccines (4.1 per million people, adjusted relative risk = 6.4 higher).

The bottom line is COVID-19 is way riskier than the COVID-vaccines in causing thrombus and contrary to a common belief the risk is not only restricted to the AZ or J&J vaccines, which use adenoviral vectors but with the COVID-19 mRNA vaccines well. This suggests it may be the immune response to the SARS-CoV-2 spike protein that induces cross-reactivity and sets up a very rare thrombotic state.  

It is never easy to explain risks and relative risks, but the following infographic doing the rounds on social media may help. What do you think? 

Please #StayCalm and #GetVaccinatedASAP

Taquet et al. Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine. OSF 15-April-2021.

Using an electronic health records network we estimated the absolute incidence of cerebral venous thrombosis (CVT) in the two weeks following COVID-19 diagnosis (N=513,284), or influenza (N=172,742), or receipt of the BNT162b2 or mRNA-1273 COVID-19 vaccines (N=489,871). The incidence of portal vein thrombosis (PVT) was also assessed in these groups, as well as the baseline CVT incidence over a two-week period. The incidence of CVT after COVID-19 diagnosis was 39.0 per million people (95% CI, 25.2–60.2). This was higher than the CVT incidence after influenza (0.0 per million people, 95% CI 0.0–22.2, adjusted RR=6.73, P=.003) or after receiving BNT162b2 or mRNA1273 vaccine (4.1 per million people, 95% CI 1.1–14.9, adjusted RR=6.36, P<.001). The relative risks were similar if a broader definition of CVT was used. For PVT, the incidence was 436.4 per million people (382.9-497.4) after COVID-19, 98.4 (61.4-157.6) after influenza, and 44.9 (29.7-68.0) after BNT162b2 or mRNA-1273. The incidence of CVT following COVID-19 was higher than the incidence observed across the entire health records network (0.41 per million people over any 2-week period). Laboratory test results, available in a subset of the COVID-19 patients, provide preliminary evidence suggestive of raised D-dimer, lowered fibrinogen, and an increased rate of thrombocytopenia in the CVT and PVT groups. Mortality was 20% and 18.8% respectively. These data show that the incidence of CVT is significantly increased after COVID-19, and greater than that observed with BNT162b2 and mRNA-1273 COVID-19 vaccines. The risk of CVT following COVID-19 is also higher than the latest estimate from the European Medicines Agency for the incidence associated with ChAdOx1 nCoV-19 vaccine (5.0 per million people, 95% CI 4.3–5.8). Although requiring replication and corroboration, the present data highlight the risk of serious thrombotic events in COVID-19, and can help contextualize the risks and benefits of vaccination in this regard

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#MSCOVID19: adenoviral vector vaccines

Barts-MS rose-tinted-odometer: ★

You may have heard that the FDA has suspended dosing of the J&J COVID-19 vaccine as they have identified 6 cases of thrombosis in young woman similar to that described below with the Oxford-AstraZeneca vaccine (see articles below).  It looks like the complication may therefore be due to the vectors, i.e. adenoviruses, rather than the SARS-CoV-2 spike protein. If this is the case there is likely to be similar cases identified with the Russian Sputnik V vaccine, which uses two different adenoviral vectors. 

Please remember that this thrombotic complication is still very rare, i.e. likely to be less than 1 person affected in over 100,000 vaccinated people, which is why the EMA, MHRA and WHO have made it clear that the potential benefit of the Ox-AX vaccine outweighs the risk of thrombosis. In other words, the risk of getting COVID-19 is far worse than the risks associated with the vaccine. So our message remains the same; #GetVaccinatedASAP.

Thrombotic (blood clots) thrombocytopaenia (low platelets) is an immune-mediated condition, in which your own immune system makes antibodies against a protein called platelet factor 4 expressed on platelets. In other words, it is an antibody-mediated autoimmune disease. This will allow haematologists and vaccinologists to study the condition and work out why it is happening and then manage the risk or hopefully prevent it from happening in the future. For example, it could simply be due to molecular mimicry to a protein or stretch of protein in one of the adenoviral proteins that could be engineered out of the next generation of vaccines. 

With my preventive medicine hat on I am concerned that this rare complication of the adenoviral vaccines will feed the anti-VAXX lobby and turn people off having the COVID-19 vaccine. This would be a great tragedy as it is the adenoviral vaccines that are going to save the world from this pandemic; they are relatively cheap and easy to manufacture and don’t have to be stored at -20 or -80. All these attributes make them the vaccines of choice for low and middle-income countries. 

Please note I would not have a problem being vaccinated with a COVID-19 adenoviral vaccine nor would I have a problem recommending these vaccines to my family members. 

Greinacher et al. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med. 2021 Apr 9. doi: 10.1056/NEJMoa2104840. Online ahead of print.

Background: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder.

Methods: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay.

Results: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity-purified antibodies in 2 patients confirmed PF4-dependent platelet activation.

Conclusions: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).

Schultz et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N Engl J Med. 2021 Apr 9. doi: 10.1056/NEJMoa2104882. Online ahead of print.

We report findings in five patients who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the ChAdOx1 nCoV-19 adenoviral vector vaccine against coronavirus disease 2019 (Covid-19). The patients were health care workers who were 32 to 54 years of age. All the patients had high levels of antibodies to platelet factor 4-polyanion complexes; however, they had had no previous exposure to heparin. Because the five cases occurred in a population of more than 130,000 vaccinated persons, we propose that they represent a rare vaccine-related variant of spontaneous heparin-induced thrombocytopenia that we refer to as vaccine-induced immune thrombotic thrombocytopenia.

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Russian Roulette

If you were invited to play Russian roulette would you do it with COVID-19 or the COVID-19 vaccine?

Russian roulette is a lethal game of chance; you place a single round in a revolver, you spin the cylinder, place the muzzle of the gun against your head before pulling the trigger in hope that the loaded chamber does not align with the firing pin, which would cause the revolver to fire and kill you.

Most people would argue Russian roulette is a voluntary game and that you can opt-out of playing it if you want. This is not the case with COVID-19 Russian roulette. You can either become immune by being infected with the SARS-CoV-2 virus or by having one of the COVID-19 vaccines. As this virus is going nowhere soon and is likely to mutate and become endemic, i.e. remain circulating in the human population forever, you will at some stage get infected with this coronavirus or one of its variants. Yes, at some point everyone who is not self-isolating as a hermit on a deserted island will get some form of COVID-19. So you need to decide: do you want to take your chances with COVID-19 and the morbidity (sickness) and mortality (death) associated with it or have one of the COVID-19 vaccines. In other words, you need to choose your poison

For example, if you are between 40 and 50 years of age you have about 1 in 1000 chance of dying from COVID-19, a 1 in 300 chance of needing a ventilator or ITU admission, a 1 in 100 chance of needing to be hospitalised and 1 in 10 chance of getting long-COVID. On the other hand, if you have the vaccine you have about an 80% chance of getting a sore arm and some minor flu-like symptoms for a few days after the vaccine and if you have advanced MS you may notice a transient worsening of symptoms, similar to what happens when you have an infection and a temperature. These symptoms can largely be prevented or made milder by taking paracetamol and/or ibuprofen prophylactically. But the risk of the vaccine revolver firing and you developing a major rare potential complication from one of the vaccines is so small (probably in the order of 1 in 100,000 or even 1 in a million) that it can’t be compared to the risks of COVID-19.

Please remember that the very rare reported adverse events such as blood clots, disseminated coagulation. immune thrombocytopenia, transverse myelitis, sudden death, etc. have not necessarily been caused by the vaccine, they may simply be what is happening as part of the background rate of these disorders in the general population. You have to realise that when you are vaccinating the whole adult population shit will still be happening in the background; i.e. people will be getting DVTs, pulmonary emboli, myocardial infarctions, pneumonia, Bell’s palsy, etc. Life and biology continue as normal and all that has changed is that a vaccine is added to the mix. So when the EMA and MHRA say the benefits of these vaccines outway the risks; their advice is based on safety data from tens of millions of vaccinated adults. Their message can’t be any clearer: #GetVaccinated these #VaccinesAreSafe.

The European politicians have been irresponsible and simply stoked the fears people already have about these and other vaccines. This will not only cost European lives but will impact the uptake of vaccines in low and middle-income countries as well. This is tragic as the Astra-Zenica vaccine is the one that is going to play a major role in stopping the pandemic in these countries. Why do politicians employ and pay experts to work for the European Medicines Agency when they simply ignore their advice? Is there a more cynical or political reason to explains their motivation?

Now getting back to the point I made at the beginning of this post; if you are forced to play Russian roulette would you do it with COVID-19 or the COVID-19 vaccine?

I promised myself not today any more COVID-19 blog posts, but one of our MS nurses asked me to write this post. Hopefully, this will be the last one I do ;-(

Age-specfic mortality:
Levin et al. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications. European Journal of Epidemiology volume 35, pages1123–1138(2020).

COVID-19 Severity and ITU admissions:
Pijls et al. Demographic risk factors for COVID-19 infection, severity, ICU admission and death: a meta-analysis of 59 studies. BMJ Open. 2021 Jan 11;11(1):e044640.

Long COVID-19:
ONS. The prevalence of long COVID symptoms and COVID-19 complications. 20-Dec-2020
Around 1 in 5 respondents testing positive for COVID-19 exhibit symptoms for a period of 5 weeks or longer
Around 1 in 10 respondents testing positive for COVID-19 exhibit symptoms for a period of 12 weeks or longer

Oxford-AstraZeneca adverse event profile:
Voysey et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111.

#MSCOVID19: transverse myelitis is not a reason to avoid being vaccinated

Barts-MS rose-tinted-odometer: ★★★

I am getting an increasing number of emails and direct messages on social media platforms about the transverse myelitis (TM) risk and COVID-19 vaccines; in particular the Oxford-AstraZeneca (Ox-AZ) vaccine. Some of the people who have contacted me have decided to forgo the vaccine and take their chances with COVID-19 and its potential sequelae. 

I want to stress that at present the link between COVID-19 vaccination and TM is very tenuous and arguably not there. Contrary to what misinformation is out there 3 cases of TM did not occur in relation to the Ox-AZ vaccine. This is the data as presented by the EMA in their ‘COVID-19 Vaccine (ChAdOx1-S [recombinant]) RISK MANAGEMENT PLAN’:

“There were 3 serious adverse events (SAEs) of demyelinating disease: 2 cases in the Ox-AZ group (1 case of transverse myelitis, and 1 case of multiple sclerosis in a participant with pre-existing, but previously unrecognised, multiple sclerosis), and 1 case of myelitis in the control group.” (EMA-ChAdOx1-S RMP)

It is important to realise that the subject with MS had signs of MS disease activity that predated vaccination, i.e. the vaccine did not cause the MS. This means that the two cases of TM were balanced between the Ox-AZ and the control arm (meningococcal vaccine).  

So the cynical anti-Vaxxers will argue that the TM is simply due to vaccination and a strong argument not to be vaccinated. So how common is TMTM post-vaccination?  

“The association between vaccines and acute demyelinating events has been assessed in a range of studies and expert reviews, including a population-based analysis of nearly 64 million vaccine doses in the US, which concluded that if there is an association between transverse myelitis and vaccines, it is < 2 per million doses of live-zoster and live-attenuated influenza vaccines, and < 1 per million doses for other vaccines (Baxter et al 2016). Moreover, demyelinating diseases occur more frequently with infections than with vaccination (Miravalle et al 2010). Taken together, the evidence is inconclusive regarding a causal relationship between contemporary vaccines and acute demyelinating events (Principi and Esposito 2020, Mouchet et al 2018, Phillips et al 2018).” (EMA-ChAdOx1-S RMP)

I suspect that TM post-COVID-19 will turn out to be commoner than TM post-COVID-19-vaccination. I have already done a blog post about the former, i.e. TM occurring in people who have had SARS-CoV-2 infection.

The annual incidence of TM ranges from 1.34 to 4.60 cases per million but increases to 24.6 cases per million if acquired demyelinating diseases like MS and neuromyelitis optica (NMO) are included. The John Hopkins COVID-19 site states that worldwide over 300M people have already received at least one dose of a COVID-19 vaccine and over 30M have received two doses as of the 8th March 2021. I think this number of COVID-19 vaccinations would be sufficient to see a TM signal. The one signal that we thought may have emerged was Bell’s palsy, but the number of cases seems to be in keeping with the background rate in the general population. Bell’s palsy was seen in the phase 3 Ox-AZ trial, but again the number of events was balanced. 

“Nonserious AEs of facial paralysis occurred in 3 participants in the Ox-Az group and 3 participants in the control group.” (EMA-ChAdOx1-S RMP)

“The MHRA continues to review cases reporting Bell’s Palsy and to analyse case reports against the number expected to occur by chance in the absence of vaccination (the ‘natural rate’). The number of reports of facial paralysis received so far is similar to the expected natural rate and does not currently suggest an increased risk following the vaccines. We will continue to monitor these events, including through the evaluation of electronic healthcare record data.” (MHRA Coronavirus vaccine – weekly summary of Yellow Card reporting, 4th March 2021)

The MHRA safety data has not shown a TM signal with either of the vaccines and that is now with millions of doses of vaccine given. 

Please remember a lot of patients with TM go onto develop MS. Thousands of people with MS have now had one of the vaccines and the last I had heard only 6 relapses had been reported to the MHRA; a very low number considering how many MS relapses occur in the UK every year. No signal has emerged in Israel either with TM or MS relapses post COVID-19 vaccination. The one caveat about Israel’s data is that it is dominated by the Pfizer-BionTech vaccine. 

As the plan is to vaccinate the whole adult population there will be people who get TM post-vaccination. This will happen by chance. Unless there are large numbers of cases of TM, as what happened with Guillain-Barre Syndrom (GBS) after the H1N1 flu vaccine, it will be very difficult to prove causation. 

Nobody is being forced to be vaccinated. If you don’t want to be vaccinated just say no, but if you decided not to be vaccinated you need to realise that you are likely at some point to get COVID-19. SARS-CoV-2 is almost certain to become an endemic viral infection, i.e. the virus won’t disappear. So you need to think about the risks that getting COVID-19 entails. In general, most people who get COVID-19 are likely to get mild to moderate disease, but there are no guarantees that you won’t get the severe disease with the potential to die. Then there is the issue of long COVID-19, which affects about 10% of people who get COVID-19. So not having the vaccine has it own risks.

My advice remains the same: #GetVaccinated ASAP; TM is not a reason to avoid the vaccines and it is not a reason to avoid the Ox-AZ vaccine either. 

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211