There has been a lot of comments on this blog about private carers and private healthcare workers not been eligible for COVID-19 vaccination under the current NHS England vaccine priority system.
I have just discovered that government guidelines don’t distinguish between public or private employees. So if you are an active healthcare worker, working in the private sector, you are eligible for the vaccine. All you need to do is call your GP and book an appointment for a vaccination. I assume if your GP doesn’t know you very well you may need to provide some form proof of your type of employment.
I would expect the same rules to apply to carers of very vulnerable people with MS. So if you are a carer and look after vulnerable people with MS and are employed privately you also need to contact your GP to make an appointment to be vaccinated. You don’t want to be responsible for potentially infecting the person you care for with coronavirus.
It is important to stress that the whole purpose of the priority vaccination programme is to protect vulnerable people from COVID-19, to protect the NHS and to save lives. It is now obvious to me that this applies to both public and private sector workers.
If your GP refuses to offer you a vaccine I suggest reiterating the above and letting us know how it goes.
I think COVID-19 has just cancelled the flu season.
I and many public health officials were very concerned that we were heading for a double-whammy this winter with a second and third surge of COVID-19 and a bad influenzae pandemic superimposed on it. It is looking like this may not happen. In the Southern hemisphere, including my country South Africa, it seems as if the flu season was cancelled. Incredibly the number of documented annual cases has dropped by over 99% (see table below).
Country
2018
2019
2020
Argentina
1517
4623
53
Chile
2439
5007
12
Australia
925
9933
33
SouthAfrica
711
1094
6
Documented cases April through mid-August. Source Science 28-Aug-2020
It is clear that the behavioural changes we have put in place, such as social distancing and wearing of masks, has prevented the spread of influenzae virus. Will these behaviours become the new norm during future flu seasons? I am not sure if people realise that influenzae is one of the biggest infectious disease killers each year so preventing the spread of the virus via behavioural change makes sense.
Saying this the UK Government has just ordered many more doses of influenzae vaccines than it normally does and is extending the so-called at-risk adult group who can get the vaccine free on the NHS this year.
Does this change our recommendations regarding getting the annual flu-jab? No, it doesn’t. All pwMS should take up the offer by the NHS to get the annual flu vaccine.
Please note, if you are severely immunosuppressed and have small children, please make sure they don’t get the live intranasal flu vaccine at school. There is a risk that this attenuated vaccine strain, which they may bring home, will cause disease in severely immunocompromised subjects. If you want your children to be vaccinated against influenza they will need to be given the component vaccine by injection. The latter is done via GP practices and some pharmacists. Please note it is only patients recently treated with alemtuzumab and HSCT that fall into this category.
I suspect that after reading the post on complications in the Oxford-AstraZeneca coronavirus vaccine study many of you are nervous about vaccinations in general. Please don’t be. The regulatory authorities assess the efficacy and safety of all vaccines and make an informed decision that at a population level the risks justify the benefits. Influenzae vaccination is the most studied vaccine in pwMS and it has been shown to be safe, i.e. it does not appear to trigger relapses and/or MRI activity.
You will have heard by now that AstraZenca has paused its coronavirus vaccine study because of safety concerns. A study subject who received the vaccine developed transverse myelitis and had to be admitted to hospital.
“The woman’s diagnosis has not been confirmed yet, but she is improving and will likely be discharged from the hospital as early as Wednesday”, said Soriot AstraZenca’s CEO (source STAT News).
From the same press conference, we also found out that another study subject had developed multiple sclerosis after receiving the vaccine. As most of you are aware transverse myelitis may be the initial manifestation of MS and sometimes it is very difficult to differentiate non-MS related transverse myelitis from CIS (clinically isolated syndrome compatible with demyelination or MS).
Are two swallows enough to make a summer? I suspect not and I would be surprised if the data and safety monitoring committee recommends stopping the trials. However, they may do so if there is a third or fourth case.
Transverse myelitis (TM) is well described after vaccination as well as after viral and other infections. The yellow fever vaccine is probably the most common cause of vaccine associated TM. However, it was a common adverse event with the original rabies vaccine that was cultured and isolated from monkey neuronal cells. Fortunately, this is not how the rabies vaccine is made anymore and the incidence of TM is now much less common after rabies vaccination. Other vaccines that can trigger TM are influenzae, MMR, Japanese B encephalitis, hepatitis B and HPV vaccines. TM has also been associated with many infections, particularly viral and some bacterial infections. We neurologists refer to this type of TM as being vaccine-associated or post-infectious TM, respectively.
Even if the AstraZenca vaccine trials restart, which in my opinion is likely, and the vaccine is shown to be effective, it is likely that the regulatory authorities will include TM as a potential adverse event. The latter will be based on the recent case and the historical perspective of other vaccines being known triggers of TM. What they will do about the case of MS is anyone’s guess, but I suspect they will include triggering MS disease activity as a potential adverse event as well. If they do this this will cause the MS community to probably err on the side of safety and hence this particular coronavirus vaccine will not be recommended for people with MS.
Other implications is that there is a chance that the TM has not been induced by the Chimpanzee Adenovirus vector that is being used in this vaccine, but the actual coronavirus spike protein or immunogen. It is noteworthy that several cases of COVID-19 related TM have already been reported in the literature (see below), suggesting it may be the virus or the spike-protein that is the culprit. If this proves to be the case then it is really bad news as TM will be a problem for the whole class of vaccines using the spike protein as the immunogen.
So the implications of these observations are enormous for the field. However, there are things that can be done by neuroimmunologists to study the immune response to the SARS-CoV-2 spike protein and the Chimpanzee Adenovirus vector to see if there is any cross-reactivity with proteins and lipids in the spinal cord. The latter are standard molecular mimicry studies and this could help AstraZeneca and other vaccine manufacturers understand the TM risk in more detail.
You have to realise that this is what happens with vaccine and drug development and underscores why drug and vaccine development is so risky and expensive. The investment costs in terms of this vaccine have been largely derisked for AstraZenca by most of the preclinical development being funded and done by academia and the fact that the British and other governments have pre-ordered millions of doses of vaccine.
We will update you on this story as it evolves.
Addendum: the published case reports of TM-like conditions occurring in association with COVID-19.
1.
Acute transverse myelitis after COVID-19 pneumonia.Munz M, Wessendorf S, Koretsis G, Tewald F, Baegi R, Krämer S, Geissler M, Reinhard M.J Neurol. 2020 Aug;267(8):2196-2197. doi: 10.1007/s00415-020-09934-w. Epub 2020 May 26.PMID: 32458198 Free PMC article. No abstract available.
2.
Transverse Myelitis in a Child With COVID-19.Kaur H, Mason JA, Bajracharya M, McGee J, Gunderson MD, Hart BL, Dehority W, Link N, Moore B, Phillips JP, Rogers D.Pediatr Neurol. 2020 Jul 29;112:5-6. doi: 10.1016/j.pediatrneurol.2020.07.017. Online ahead of print.PMID: 32823138 Free PMC article. No abstract available.
Transverse myelitis related to COVID-19 infection.Zachariadis A, Tulbu A, Strambo D, Dumoulin A, Di Virgilio G.J Neurol. 2020 Jun 29:1-3. doi: 10.1007/s00415-020-09997-9. Online ahead of print.PMID: 32601756 Free PMC article. No abstract available.
Anti-CD20 therapy not only increases your chances of getting COVID-19 but also increases your chances of developing severe COVID-19 and having to be admitted to hospital for treatment. I have argued that the likely mechanism is to be due to anti-CD20 therapies blunting important cross-reactive anti-coronavirus immune response acquired from other community-acquired coronaviruses. If this is correct it means that people with MS (pwMS), and other diseases, on anti-CD20 therapies, will be unlikely to mount protective immune responses to ane effective SARS-CoV-2 vaccine.
Based on the questions I have been asked on social media and recent COVID-19 related webinars vaccine readiness is clearly playing on the minds of many HCPs and pwMS. To provide some perspective we have recently written a review paper on vaccine readiness to highlight this topic and to how to mitigate this issue.
It seems likely that pwMS on anti-CD20 therapies are going to have to take a drug holiday to allow peripheral blood B-cell reconstitution before being vaccinated. What I don’t know is whether or not this hypothesis is correct and if correct what level of B-reconstitution will be necessary to allow an adequate vaccine response. I, therefore, propose testing this in a clinical trial where we compare antibody and T-cell responses to the SARS-CoV-2 vaccine when it emerges with different levels of peripheral B-cell reconstitution. The idea will be to vaccinate patients at different time points after early and late (above normal) peripheral blood B-cell reconstitution. I have called this trial the COVAX Study or the “Coronavirus Ocrelizumab VA(X)ccination Study”.
If you are on ocrelizumab would you volunteer to participate in this study?
Although most autoimmune diseases are considered to be CD4 T-cell or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab that is used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities, notably multiple sclerosis, where ofatumumab is in late stage development and ocrelizumab is approved for use. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of multiple sclerosis and COVID-19, it was hypothesised that whilst B-cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B-cell subset inhibition that controls multiple sclerosis and other autoimmunities, would not influence innate and CD8 T-cell responses, which are central to SARS-CoV-2 elimination, nor the hyper-coagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority (mortality rate n=~5/392) of SARS-CoV-2 infected, CD20-depleted people with multiple sclerosis have recovered. However, protective neutralising-antibody and vaccination responses are predicted to be blunted, until naïve B-cells repopulate, based on B-cell repopulation-kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose-interruption to maintain inflammatory disease control in MS and other autoimmune diseases, whilst allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.
Not walking my talk. Having not taken up the NHS offer of the seasonal flu vaccine and having just spent the last 3 days bed-bound with severe flu I found the following research paper very timely.
Using the Norwegian registries these investigators show that pwMS are much more susceptible to the complications of influenza, i.e. pwMS are much more likely to require emergency hospital admission as a result of influenza infection. Reasons for this are three-fold. Firstly, people with advanced MS may not have as strong gag and cough reflexes with a higher chance of aspiration of their secretions with secondary pneumonia. They may also have weakened respiratory muscles that increase their chances of getting a segmental collapse of their lungs and secondary pneumonia. Secondly, many pwMS are on immunosuppressive medications which blunt their immune response to the influenza virus making the virus more virulent and likely to affect multiple organ systems. Finally, on average pwMS have reduced resilience to infections independent of being on immunosuppressive medication, this probably relates to deconditioning, temperature-related conduction-block in response to fever and the fact that many pwMS are disabled. In summary, pwMS handled infections less well than the general population and are more likely to get complications.
Disappointing is the observation that pandemic vaccination did not influence the risk of hospitalization in this study. I suspect this was because the pandemic vaccine used in this study epoch was not effective.
Even if you don’t need hospitalisation having influenzae is very unpleasant and make your MS symptoms much worse. There have been some studies that have shown that not all patients recover back to their baseline when they get worsening of their MS symptoms in response to an infection. The latter observation would imply that the infection triggered an MS relapse. Avoiding infections is, therefore, one of our aims as part of the holistic management of MS.
As I sit here and type this blog post I am still incredibly tired with brain fog and many persistent symptoms that will take a week or more to clear. The physical symptoms are one thing, what about the social impact? I just spent the three days of the festive season in bed ignoring my family and social commitments. The bottom line is if you can avoid having flu, why wouldn’t you? It is not too late to be vaccinated.
Patients with multiple sclerosis (MS) are at increased risk of infections and related worsening of neurological function. Influenza infection has been associated with increased risk of various neurological complications. We conducted a population-based registry study to investigate the risk of acute hospitalization of MS patients in relation to influenza infection or pandemic vaccination in Norway. The entire Norwegian population in the years 2008-2014 was defined as our study population (N = 5,219,296). Information on MS diagnosis, influenza infection and vaccination were provided by Norwegian national registries. The self-controlled case series method was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CI) in defined risk periods. 6755 MS patients were identified during the study period. Average age at first registration of an MS diagnosis was 51.8 years among men and 49.9 years among females (66.9%). The IRR for emergency hospitalization among MS patients the first week after an influenza diagnosis was 3.4 (95% CI 2.4-4.8). The IRR was 5.6 (95% CI 2.7-11.3) after pandemic influenza, and 4.8 (95% CI 3.1-7.4) after seasonal influenza. Pandemic vaccination did not influence risk of hospitalization [IRR within the first week: 0.7 (95% CI 0.5-1.0)]. Among MS patients, influenza infection was associated with increased risk for acute hospitalization while no increased risk was observed after pandemic vaccination. Influenza vaccination could prevent worsening of MS-related symptoms as well as risk of hospitalization.
