Tag: COVID-19

Re Private Healthcare Workers and Carers

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.

#MSCOVID19: yes, have the vaccine

Barts-MS rose-tinted-odometer: ★★★★★

Despite the long blog post that I called CATCH-22 I am still getting numerous emails and questions from patients with MS about whether or not they should have a COVID-19 vaccine.

YES, you should have the vaccine when it is offered to you. Clearly, timely access to the vaccine will depend on where you live, how vulnerable you are and the local, regional and national guidelines in place in your own country. 

The benefits of COVID-19 vaccination is time-sensitive and if you wait to be vaccine-ready you may inadvertently acquire the coronavirus infection and become really ill or when you are vaccine-ready the pandemic and the at-risk period may have passed. 

In my opinion, some immunity is better than no immunity and the blunted vaccine immunity on some DMTs may be sufficient to prevent you from becoming infected with SARS-CoV-2, developing COVID-19 and more importantly developing severe COVID-19. 

Are the vaccines safe? No vaccine is 100% safe, but the fact that the regulatory authorities have licensed these vaccines indicates that the benefits of the vaccine far outweigh the risks associated with the vaccine in the general population. At the moment the only relative contraindication to the Pfizer-BioNTech RNA vaccine is a history of severe atopy or allergies, i.e. people who carry around an epi-pen to prevent anaphylaxis in response to an environmental allergen.  

If you have any questions please read the CATCH-22 blog post, and our new advice here. If these don’t answer your question(s) we will try and address them below.

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?

CoI: multiple

Twitter: @gavinGiovannoni                                              Medium: @gavin_24211

#MSCOVID19: CATCH-22

Barts-MS rose-tinted-odometer: ★

I know it sounds like a cliche but Catch-22 would definitely be on my list of most impressionable books I read as a teenager.  I liked it because of its dark satirical humour, it was written in the third-person and it taught me how absurd war actually is. Catch-22 (and the Great Gatsby) also taught me if you love a book you should never watch the movie; the screenwriters, actors and directors can never do your imaginary characters justice. 

The book has become so influential that ‘Catch-22’ has become a noun and refers to a dilemma or difficult circumstance from which there is no escape because of mutually conflicting or dependent conditions. 

Although I am meant to be at home recovering from injuries I am doing some emails. Over the last few days, I have received numerous emails from patients and neurologists asking for advice about COVID-19/SARS-CoV-2  vaccines and DMTs and what am I telling my patients. One patient tells me that her neurologist referred her the excellent MS Society webpage for advice, but the site then referred her back to her neurologist for definitive advice. A Catch-22?

Some US neurologists have picked-up that my advice and position on vaccines and vaccine readiness has changed since I first started talking about this issue on the blog. They are correct, my position has changed. I always took the position that we should continue to manage MS the way we managed it before COVID-19 with certain caveats* around the risk of being exposed to SARS-CoV-2 and whether or not individuals could self-isolate or not, and that we should cross the vaccine bridge when it arrives. Now that the vaccines are arriving and the ambitious national roll-out suggests the whole country will be vaccinated within the next 6 months, advice has to be given and given quite quickly. 

In my opinion, all the COVID-19 vaccines that the UK Government has purchased can be used in people with MS regardless of whether or not they are on a DMT. This advice is based on the fact that the MHRA and other regulatory bodies have licensed or will license these vaccines because of their safety and efficacy profile in the general population. 

Importantly none of these vaccines is likely to be a ‘live viral vaccine’. There is some confusion around the Oxford-AstraZeneca vaccine that does use a chimpanzee adenovirus vector to deliver the immunogen to our cells so that the immunogen can be expressed. The virus in this vaccine is able to infect cells and express its relevant proteins, but because some of its genes for replication have been mutated it cannot replicate itself and cause ongoing infection. I am not sure how this vaccine will be classified by the MHRA or other regulatory authorities, but in my opinion, it is likely to be safe to use in pwMS. 

I say these vaccines are likely to be safe in pwMS. However, none of the COVID-19 vaccines has specifically been tested in pwMS so we have to extrapolate data from the general population data. There may be something we don’t know about having MS that predisposes pwMS to some rare complications. However, based on other vaccines that have been used in MS this is very unlikely. 

It is clear that being on some immunosuppressive DMTs may reduce your chances of responding adequately to the vaccine and hence being fully immune to infection from wild-type SARS-CoV-2. Until we do detailed immunological studies in pwMS on each DMT we won’t be able to answer specific questions about each DMT with certainty. 

Interferon-beta , glatiramer acetate and immune reconstitution therapies

In general being on interferon-beta and glatiramer acetate, immunomodulatory DMTs, are unlikely to interfere with vaccine responses. Similarly, if you have had one of the immune reconstruction therapies, such as alemtuzumab, cladribine, mitoxantrone or HSCT in the past and have reconstituted your peripheral immune system you should respond to the vaccines. If on the other hand, you have not had completely reconstitution of your immune system you may still consider having the vaccine, but the immune response may be blunted. Waiting for immune reconstitution or having the vaccine now will be a trade-off between wanting to protect yourself now or waiting months when the pandemic may be almost over. Please note vaccination is not only about you, but slowing and preventing transmission of the virus in the general population, which is a factor you may want to consider. This may relevant, for example, if you want to see unvaccinated vulnerable relatives or if you want to travel to parts of the world with a delayed vaccination programme.  

Fumarates, teriflumide and natalizumab

If you are fumarates (DMF,  diroximel fumarate), teriflunomide or natalizumab, based on other vaccine studies, COVID-19 vaccine responses are likely to be reasonably preserved. Therefore there is no need to stop these DMTs or delay getting a vaccine if you are on these treatments. 

S1P modulators

For the so-called S1P modulators (fingolimod, siponimod, ozanimod and ponesimod) vaccine responses are likely to be blunted, but whether or not the blunted responses will be sufficient to prevent SARS-CoV-2 infection is a moot point.  However, I would not recommend stopping these treatments to have a vaccine as these therapies are associated with MS rebound activity. My advice would be that if you are on these therapies to go ahead with the vaccine when it is offered to you. 

Anti-CD20 therapies

When I initially wrote about vaccine hesitancy I suggested that pwMS on an anti-CD20 therapy (rituximab, ocrelizumab, ofatumumab) may have to delay their next infusion or miss one or two infusions to allow B-cell reconstitution before they have a coronavirus vaccine. Since making this statement more immunological data has emerged and there really is no definitive evidence to support this position. 

Yes, I agree that in general people on anti-CD20 therapies have blunted antibody responses to wild-type SARS-CoV-2 infection and to other vaccines including vaccines with containing new antigens that the immune system has not seen before. However, this doesn’t mean these people haven’t developed immunity to the infection or vaccine that is long-lasting. For one the vast majority of pwMS on an anti-CD20 therapy who get COVID-19 make an uneventful recovery. Why? Almost certainly this recovery is due to cellular and not humoral (antibody) immunity and this immunity won’t vanish and is likely to persist longterm. 

Even normal people who have had COVID-19 and who lose their antibody responses still have detectable cellular immunity. My interpretation of this data is that pwMS who are on an anti-CD20 therapy should simply go ahead and have the coronavirus vaccine when it is offered to them and not to worry about whether or not they mount an antibody response. 

I am aware that some pwMS are planning to delay their next infusion regardless of what I or their HCP says. The question I ask is for how long? One, two, three or more months? Some pwMS plan to wait for peripheral B-cell reconstitution that can take months to years to occur and even then there is no consensus of what normal B-cell reconstitution looks like. You need to weigh the lack of evidence that delaying your next anti-CD20 therapy or waiting for B-cell reconstitution will make any difference to your vaccine response against the time-sensitive nature of the vaccine to protect you during the high-risk period of the pandemic. If you wait too long and the pandemic is over the benefits of the vaccine will be reduced. 

The only evidence base we have at the moment is the recently published VELOCE study that delayed vaccination until 12 weeks after an initial course of ocrelizumab. This study showed blunted, but not absent, antibody responses to recall and new vaccines. Based on this study if you have just had a recent course of ocrelizumab you may want to delay getting the COVID-19 vaccine for 12 weeks after the last infusion. However, as 12 weeks is a long time to wait in the current climate I have been recommending at least 4 weeks; a pragmatic compromise.

In my opinion, it is more important for pwMS on anti-CD20 therapies to be vaccinated than to not be vaccinated. This is because vaccination policy is really about population, or subpopulation, health and stopping the spread of the virus and protecting the individual is a secondary aim. 

MS relapses

Will the COVID-19 vaccines trigger MS relapses? This hypothesis is based on extrapolating data on two non-peer-reviewed cases of CNS demyelination in the Oxford-AstraZenca (Ox-AZ) trial and several cases of transverse myelitis in patients who have had COVID-19. One case on in the Ox-AZ trial, who received the vaccine, had an initial attack or relapse and was subsequently diagnosed as having MS; i.e. I assume because they had pre-existing lesions and were now shown to have a second attack or new lesions consistent with dissemination in time. The other case had an episode of vaccine-related transverse myelitis (TM), which is relatively common with vaccines in general. Please note that vaccine-related TM is not MS. The only vaccine that has been reported to potentially trigger MS relapse is the live yellow-fever vaccine and this is based on one report that has subsequently not been replicated. Therefore, there is no current evidence that coronavirus infection or coronavirus vaccines trigger MS relapses. In my opinion, there is no reason to avoid the COVID-19 vaccine based on this hypothesis. Clearly, my opinion may change if new data emerges to the contrary.

Summary

If you have not had COVID-19 having a vaccine will offer you the opportunity of preventing getting COVID-19 or at least if you do get it, of having milder disease. All the licensed vaccines, which have been shown to be safe in the general population are likely to be safe in pwMS. Although some people on immunosuppressive therapies, in particular, S1P modulators and anti-CD20 therapies, may have blunted antibody vaccine responses these may still be sufficient to protect you against infection or at least severe COVID-19. There is no evidence that stopping or delaying treatment, in the hope of boosting vaccine responses will work and may result in you missing out on being protected when your risk of infection is highest. Please be aware that stopping some DMTs, in particular, natalizumab and S1P modulators, is associated with a rebound of disease activity and is not recommended. Hopefully, the pharmaceutical industry and the wider MS community will collect data and do specific studies to answer the many questions we have around vaccination and vaccine responses in pwMS on specific DMTs. 

* The caveats refer to alemtuzumab and HSCT, which affect both innate (monocytes and/or neutrophils) and adaptive (particularly cytotoxic CD8+ T lymphocytes), which are required for fighting SARS-CoV-2. My advice for the other DMTs has not to self-isolate, but to simply stick to the current government guidelines in relation to social distancing and personal hygiene. 

Bar-Or et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology October 06, 2020; 95 (14) 

Objective: The phase IIIb VELOCE study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis.

Methods: Patients were randomized 2:1 into Group OCR (n=68; OCR 600mg); or Control (n=34;interferon-β or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax® (23-PPV) and keyhole limpet hemocyanin (KLH). Group OCR was subdivided into OCR1 (n=33) and OCR2 (n=35) at randomization. OCR1 received Prevnar® (13-PCV) 4 weeks after 23-PPV; OCR2 and Control received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (Group OCR) or on Day 1 (Control).

Results: Positive response rate to TT vaccine at 8 weeks was 23.9% in OCR vs 54.5% in Control. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in OCR and 100% in Control. Prevnar® did not enhance response to pneumococcal serotypes in common with Pneumovax®. Humoral response to KLH was decreased in OCR vs Control. Seroprotection rates at 4 weeks against five influenza strains ranged from 55.6–80.0% in OCR2 and 75.0–97.0% in Control.

Conclusion: Peripherally B-cell depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen, KLH, suggesting use of standard non-live vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR, as a potentially protective humoral response, even if attenuated, can be expected. Classification of evidence This study provides Class II evidence confirming that the humoral response to non-live vaccines in patients with RMS following ocrelizumab treatment is attenuated compared with untreated or interferon-β–treated patients, though can still be expected to be protective.

Twitter: @gavinGiovannoni                                   Medium: @gavin_24211

Bring back the experts

Barts-MS rose-tinted-odometer: ★★

“I think the people of this country have had enough of experts”, Michael Gove, June 2016.

Of the many positive things to come out of the COVID-19 pandemic and our response to it is the end of the era of denigrating the expert. Yes, expertise and in particular deep expertise really matters and that applies to the diagnosis and management of multiple sclerosis. 

What is the difference between expertise and deep expertise? For example, I am registered by the General Medical Council in the UK as a neurologist and hence a medical expert in the practice of neurology. This means I can see, diagnose and manage anybody with a neurological problem. However, my sub-speciality is multiple sclerosis and related diseases (deep expertise). If you had a myopathy or a disease of muscles would really want me to be your treating neurologist. I suspect not; you would probably want to see a neurologist who specializes in muscle diseases. Although, I can quite easily read about the latest evidence and research into myopathies and give you an expert opinion, as I don’t have the day-to-day experience (deep expertise) in managing patients with myopathy you would not be given the best advice. Who knows if my self-directed rapid myopathy update would be good enough?  Would I have enough insight and experience to only read the best most up-to-date evidence or would I be influenced by some whacky off-the-wall myologist (muscle expert)?

We need, more than ever, a serious pushback on ‘fake news sites’, ‘lobby groups with vested interests’, ‘social media groups without expert input’ and ‘anti-science movements with unsubstantiated conspiracy theories’ to name the most obvious.

We also need to understand and learn to live with and be comfortable with uncertainty. Yes, that means accepting that experts may disagree with each other. Science is not black-and-white and is usually grey and as more evidence emerges and innovations or ideas become adopted or accepted the colour or advice becomes closer to being black or white. Science and the acceptance of science take time.

This is where inspired leadership comes into play. In any field, there are leaders who have the necessary reputations and trust that people will follow their advice. These leaders are often good communicators and have the uncanny ability to provide a balanced view of the state of play when the evidence is not black-and-white and they can communicate uncertainty in a way that makes sense and is understandable to the general public. Dr Anthony Fauci, from the NIH, comes to mind with his level headed approach to the COVID-19 epidemic in the US. On the other hand, there are many examples of bad or poor leadership during this pandemic, which has resulted in squandering of political capital, confusion and lack of trust. I don’t think I need to give specific examples of poor leadership there are many obvious ones.

In the MS space, there is different advice being peddled by various groups about what to do about vaccinating people with MS on anti-CD20 therapies with the newly licensed or soon to be licensed coronavirus vaccines. I think there is broad consensus that a live replicating viral vaccine is a no-no in people on anti-CD20 therapies. However, this advice is irrelevant as the three coronavirus vaccines at the head of the queue are not live replicating virus vaccines. The Oxford-AstraZeneca vaccine uses a viral vector (chimpanzee adenovirus) to deliver the construct (nucleotide message) to express the immunogen, but it is a replication-deficient virus so is highly likely to be safe in people with MS on anti-CD20 therapies. 

Another bit of misinformation that is doing the rounds is that these vaccines will trigger MS relapses. This is based on extrapolating data on two non-peer-reviewed cases of CNS demyelination in the Oxford-AstraZenca (Ox-AZ) trial and several cases of transverse myelitis in patients who have had COVID-19. One case on in the Ox-AZ trial, who received the vaccine, had an initial attack or relapse and was subsequently diagnosed as having MS; i.e. assume because they had pre-existing lesions and were now shown to have a second attack or new lesions consistent with dissemination in time. The other case had an episode of vaccine-related transverse myelitis (TM), which is relatively common with vaccines in general. Please note that vaccine-related TM is not MS. The only vaccine that has been reported to potentially trigger MS relapse is the live yellow-fever vaccine and this is based on one report that has subsequently not been replicated. Therefore, there is no current evidence that coronavirus infection or coronavirus vaccines trigger MS relapse. This in my opinion is not a reason to avoid having the coronavirus vaccine at present. This opinion may change if new data emerges to the contrary.

Another bit of grey advice that is being peddled as black or white is that people with MS (pwMS) on anti-CD20 therapy should delay their next infusion or miss one or two infusions to allow B-cell reconstitution before they have a coronavirus vaccine. What is the evidence for this? There is no definitive evidence. Yes, I agree that in general people on anti-CD20 therapies have blunted antibody responses to wild-type SARS-CoV-2 infection and to other vaccines including vaccines with so-called neoantigens or new antigens that the immune system has not seen before. However, this doesn’t mean these people haven’t developed immunity to the infection of vaccine that is long-lasting. For one the vast majority of pwMS on an anti-CD20 therapy who get COVID-19 make an uneventful recovery. Why? Almost certainly this recovery is due to cellular and not humoral (antibody) immunity. Do you then think this cellular immunity simply vanishes? Highly unlikely. Normal people who have COVID-19 and who lose their antibody responses still have cellular immunity. My interpretation of this data is that pwMS who are on an anti-CD20 therapy should simply go ahead and have the coronavirus vaccine when it is offered to them and not to worry about whether or not they mount an antibody response. Whilst this is happening companies like Roche-Genentech (ocrelizumab & rituximab) and Novartis (ofatumumab) or the wider MS community should be funding studies to look at both antibody and cellular immunity to the coronavirus vaccines in pwMS on these therapies so that we can develop an evidence base. The data collected as part of these studies will not only be relevant to SARS-CoV-2 infections and vaccines but other infections and future vaccines. 

In my opinion, it is more important for pwMS to be vaccinated than to not be vaccinated. This is because vaccination policy is really about population, or subpopulation, health and stopping the spread of the virus and protecting the individual is a secondary aim. If you have MS and would rather wait for data to emerge on the safety and efficacy of the vaccine in the MS population it will take another 6 to 12 months, and maybe longer, and then the evidence if not collected prospectively as part of a well-controlled trial may not answer the questions you have. Also in 6-12 months, the pandemic is likely to be over and hence these questions may never get answered.  

So my gut feeling based on scientific principles is that all pwMS should be vaccinated. If the initial roll-out of vaccines means the vaccines may be rationed I would argue we prioritise pwMS (1) over the age of 50, (2) those with significant comorbidities, (3) those on immunosuppressive therapies, in particular, those on anti-CD20 therapies and natalizumab and (4) those pwMS doing essential jobs with significant face-to-face contact with the general public (healthcare workers, care workers, teachers, etc.) to get the vaccine first. 

Disclaimer: As I am not a public health or vaccine expert you need to interpret my advice with care.

Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?

CoI: multiple

Twitter: @gavinGiovannoni                                  Medium: @gavin_24211

Discharged

Good news; I was discharged from hospital yesterday morning to complete my recovery and rehabilitation at home.  

My admission to hospital has reminded me what a great institution the NHS really is. All I want to say is that the NHS care I received was exceptional; very professional and full of deep caring and empathy. The staff on the trauma, orthopaedic and neurosurgery units at King’s College Hospital are truly exceptional. Thank you so much.

During my admission, some of the medics made excuses for some of the delays we encountered in the investigations and care I received during my stay. Interestingly, I didn’t really notice these delays, nor did I complain, nor did I comment on any of the issues that made excuses about; it was if they felt compelled to make excuses for the NHS inefficiencies because I was a Professor of Neurology. I simply responded that this was not a problem. What I should have pointed out to these commentators that whilst I was in hospital there was not a day when there wasn’t a shortage of nurses on the wards. In addition, many of the medical team were off due to COVID-19; either infected with the coronavirus or self-isolating due to being in contact with someone with COVID-19. People don’t realise that when it comes to value the NHS is the best healthcare system in the world. Being the best value healthcare system doesn’t mean we should accept the status quo, but rather we have a fantastic healthcare system, i.e. a platform on which to build excellence. 

For readers who don’t live in the UK, when I was discharged yesterday, with medication for 2-weeks and a clear follow-up and rehabilitation programme, I didn’t have to pay for a single thing. Yes care under the NHS is truly free at point-of-care. 

Healthcare in the UK, similar to other European countries,  is considered a basic human need and therefore everyone should have equal access to care. This does not equate to socialism as such, which is a rather overused term. It simply means that we the citizens of the UK feel that everybody, regardless of their background, should have access to healthcare if they need it. I am a true believer in the concept of universal healthcare. Saying this there is still wide variation in the NHS in relation to access to treatments and services. This is why we started the MS Academy’s “Raising the Bar”  or “RtB” initiative three years ago to tackle variance in the provision of MS Services in the UK. 

Whilst in hospital I watched the last two days of our RtB 2020 meeting and it made me realise that the RtB initiative now has momentum that will truly improve MS services for pwMS in the UK. If you haven’t seen the three RtB presentations I would urge you to watch and to join us and to get involved. We also had a few international HCPs sign-up for the 2020 RtB meeting, which is good news.  Why shouldn’t this become an international initiative?

As you can see I am back typing albeit very slowly in a drug-induced fog. I am only able to do this lying on my back using a pair of periscope glasses that I purchased for this purpose. As a result of my nerve and neck pain, I have to spend the majority of my day lying flat on my back in a neck brace.  I am unable to bend my neck as it causes too much pain. 

In addition, my fractured pelvis, which has been fixed (see below), is still very painful when I sit or walk. So I am resigned to a long slow recovery and hence I am unlikely to back to normal or work for several months. 

Thank you so much for your continuing to support our Barts-MS Coronavirus antibody study. Since my accident, there has been a surge in donations.

I am thinking of setting myself another challenge to raise money for this initiative. At the moment I am EDSS 6.5; I can walk maybe 20 metres using crutches. Will you sponsor me to become EDSS 4.0 in 4 weeks time, i.e. to walk 500 m without crutches or support?  I am prepared to do this if you will support me as it is critical that we get the first phase of this study done before the coronavirus vaccine arrives. What do you think?

P.S. I have set-up a Just Giving page called “Prof G’s EDSS 6.5 to 4.0 Challenge“; all of the money will go to Queen Mary University of London to support Dr Ruth Dobson’s and Dr Angray Kang’s COVID-19 MS Antibody study. Thank you.

CoI: multiple

Twitter: @gavinGiovannoni  Medium: @gavin_24211

#MSCOVID19: getting ready for the vaccine

Informing patients about their potential coronavirus risks associated with anti-CD20 therapy is complicated and resulting in our patients being given different advice depending on who they see. The reason for this is that we don’t have the direct evidence to be able to dissect out why people on anti-CD20 therapy are at higher risk of COVID-19 and at higher risk of being admitted to hospital with severe COVID-19. 

I doubt this increased risk relates to increased exposure to the coronavirus. Why should someone on ocrelizumab who attends their healthcare facility be at increased risk of acquiring SARS-CoV-2 infection compared to someone for example on natalizumab who attends for their infusion every 4-6 weeks? 

The clue to the increased risk is in the detail of the data. It is apparent that the longer you have been on an anti-CD20 therapy the greater your risk; the risk of COVID-19 is particularly high if you have been on an anti-CD20 therapy for more than 3 years. This means that it must be due to prior exposures, i.e. exposures before the COVID-19 pandemic started.  

In the general population, it is now clear that some people have T-cells and antibodies that cross-react with SARS-CoV-2 and that these protect these people from developing COVID-19 or severe COVID-19. These cross-reactive immune responses are likely to have developed in response to infection or exposure to other circulating coronaviruses; the viruses that cause the common cold. 

My theory is that if you are on an anti-CD20 therapy with no B-cells and a poorly functioning antibody response and you get the common cold your immune system will not be able to make these protective cross-reactive anti-coronavirus antibodies. This would then reduce your chances of being protected from getting COVID-19 or getting only mild COVID-19 when you are infected with SARS-CoV-2. 

I have tried to illustrate this in the following slide showing that people on long-term anti-CD20 therapies are more likely to get symptomatic SARS-CoV-2 infection, i.e. COVID-19, and when they do get COVID-19 it is likely to be more severe. Severity in this context is requiring hospitalisation and potential intensive care and ventilation. 

What does this mean for you? It means that if you are about to start ocrelizumab, rituximab or ofatumumab then your chances of getting COVID-19 are unlikely to be different to another DMT, with the exception of interferon-beta that lowers your risk because of its antiviral effects. 

If you happen to be on ocrelizumab, rituximab or ofatumumab already there is little you can do, because these agents are not rapidly reversible and even if you stop the treatment and allow your B-cell compartment to reconstitute you are unlikely to develop the cross-reactive immunity from common coronaviruses. However, by stopping your anti-CD20 and allowing your B-cells to reconstitute you will be allowing your immune system to prepare itself for a coronavirus vaccine in the future.

At the beginning of the pandemic, I was a bit cynical about the chances of a successful coronavirus vaccine emerging, but the preliminary phase 2 results of several vaccines and the immunological insights above have made me much more optimistic that we will have an effective coronavirus vaccine quite soon. When I say soon I suspect we will have one ready for general consumption early next year. In all likelihood, one of the first vaccines will be the Oxford-AstraZeneca vaccine that happens to involve a live virus, which itself will have implications for some of the MS DMTs. 

If my predictions are correct the MS community may need to start getting vaccine ready or they can simply rely on herd immunity. With anti-CD20 therapy, this needs to be planned ahead and patients will need to miss one, two or possibly three infusions depending on their body size and individual B-cell reconstitution kinetics in order to prepare their immune systems for the vaccine. 

Some critics of this strategy are saying that patients on an anti-CD20 therapy will still make T-cell responses to the vaccine that will in all likelihood protect them. Yes, this may be the case, but then how do you explain the above observations that people on anti-CD20 therapy are at increased risk of COVID-19 and severe COVID-19? I would interpret this as them having blunted T-cell responses to cross-reactive common coronaviruses. If this is the case pwMS on an anti-CD20 will have blunted T-cell response to the vaccine. In support of the latter is the observation that several pwMS on ocrelizumab who have had swab-positive COVID-19 have failed to make an antibody response to the virus. Please remember that good quality antibody responses are T-cell dependent. These observations are telling me that in all likelihood being on anti-CD20 therapy will prevent you from developing protective immunity to coronavirus from a vaccine.

Clearly getting more detailed population-level COVID-19 data in people with MS is very important. This is why we are trying to crowdfund our study to identify people who have antibodies to SARS-CoV-2. We will be able to use this resource to do nested immunological studies on pwMS on different DMTs to understand the cross-reactive immunology at both the T and B cell level to coronaviruses in general and test the hypotheses above. It will also allow us to study vaccine responses if and when the vaccines arrive. 

If you are prepared to help with a small donation it would be much appreciated. Thank you.

JustGiving

CoI: multiple

#MSCOVID19: now for something completely different

I recently did a post that I called ZOOMED-OUT that was in response to spending too much time online in endless meetings, on webinars with information overload and preparing and watching too many didactic lectures. Therefore, we have changed the format of our next triMSx-online meeting into a Q&A session. If you are interested please register to find out more and to make the meeting more interactive and worthwhile.

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CoI: multiple

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