#MSCOVID19: ostrich

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Do you want to know if you have been infected with SARS-CoV-2 the coronavirus strain that causes COVID-19? With 25-50% of infections being asymptomatic or very mild you will need an antibody test to find out. 

If you are found to have antibodies to SARS-CoV-2 would you not want to know the titre or amount of antibody in your blood? And whether or not these antibodies are so-called neutralizing and capable of preventing reinfection with SARS-CoV-2?

Answering these questions is critical and underpins the strategy of allowing people to receive a so-called “COVID-19 passports”. The passport will state that you have immunity to the virus and hence you can rejoin the herd and get on with your life. 

As an MS researcher, I am also interested to know what happens to the antibody response to SARS-CoV-2 in pwMS on different DMTs. For example, are people on rituximab and ocrelizumab less likely to develop an antibody response after COVID-19 and if they do is the antibody response good quality, i.e. capable of neutralizing the virus and preventing reinfection? What about the antibody responses in people on natalizumab? On fingolimod? Post-cladribine or post-alemtuzumab? 

My predictions are that the IRTs (cladribine and alemtuzumab) and possibly natalizumab will come out on top both in term of qualitatively (neutralizing antibodies) and quantitatively (overall titre) in terms of anti-SARS-CoV-2 antibody responses. Anti-CD20s (rituximab, ocrelizumab and ofatumumab) and the S1P-modulators (fingolimod, siponimod and ozanimod) will come out on the bottom. Please note this is a hypothesis and as with all hypotheses they need to be tested in well-designed and appropriately powered studies.

Barts-MS has therefore proposed doing an antibody study of this kind, but it looks like pharma is chicken to collaborate with us. I suspect they don’t want to know the answer to the questions above. I call this the “ostrich syndrome”; you can put our head in the sand for as long as you like, but eventually, a rabid dog will come and “bite your arse”

As the MS community gears up for ensuring their patients are “vaccine ready”, who if they are SARS-CoV-2 antibody-negative (no previous infection) will want to be on a DMT that blunts or prevents an adequate vaccine response. Why take a chance if you don’t have to particularly as there are several suitable alternative DMTs? However, if the above hypotheses are disproved then most of us will be happy with the status quo.

All these arguments above are predicated on the assumption that we will get an effective SARS-CoV-2 vaccine or vaccines. Please note there is no guarantee that this will happen. I would estimate the chances of getting an effective vaccine in the next 18-24 months as being close to 80%. Optimistic? Yes, but at the same time, I am trying to be realistic.

CoI: nil

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

23 comments

  • I think it’s important that we know as much as we can about the virus, and it’s relationship with DMT’s and getting prepared for any vaccine that may or may not come along. My only concern is that I am on Ocrelizumab and I don’t think there is an alternative.

    • There are strategies with anti-CD20 that will allow you to become vaccine ready; for example, once you have been on the therapy for 18 or more months a drug holiday will allow some B-cell reconstitution and a window to be vaccinated.

      Vaccine immunity is also about T-cell responses. We know that some people who don’t develop antibodies to the measles vaccine are still immune because of cellular immunity. The same may happen with anti-CD20 therapies. In fact, cellular immunity may be more important than antibody immunity.

      • I think you’ve answered my question below here. Having said that I’ve only had my 2 halves and my first full. I was due my 2nd full dose this month. How will we know how long a gap is the optimum?

  • The chances of a vacine that is effective against COVID 19 are diminishing as there are now over 300 mutated strains of COVID 19 that have been identified! Stop one strain the other strains become dominant as all have unique spikes for vacine response. A new novel vacine is needed that recognises all flue like vacones!

    • Yes and no. There will be critical epitopes that can’t change and these are the ones that are needed in a vaccine.

    • There are vaccines that even react with both SARS and COVID already. The important bit about mutating is where are the mutations?. The Spike RBG is what makes a neutralizing antibody response, the question is if the virus mutates its SPIKE RBD does it stop binding to ACE2 and then it becomes a different disease but if it is not infecting the vaculature is it a lethal and interesting. Therefore it cant mutate certain bits too much. However do you need an antibody response or a T cell response to give you anti viral protection?

      • Thanks Prof G and MD. Ahh okay. So spike RBG is what vacine bind to it and if it changes its characteristics as a disease changes. For worse or better. Great! Guess better the devil you know

  • It definitely seems important to know which DMTs might blunt response to a COVID vaccine. I’m doubtless being naive or dense but why would pharma not want to know this as well? OK, it might make some DMTs less attractive right now, but surely others would benefit by being more sought after? As you suggest, wouldn’t the fact that some DMTs don’t correlate well with a vaccine become evident at some point anyway? And wouldn’t that rebound badly on pharma (not to mention pwMS)?

  • For those of us on ocrelizumab, albeit delayed at present, how long a gap should be allowed between infusions in order to be vaccine ready? This is obviously dependent on when the vaccine is available though.

    • We don’t know and it is premature to do this. We need the antibody and cellular immunity studies to be done first. For all, we know pwMS on ocrelizumab make very good (protective) antibody and cellular immune responses and then there may be no need to take a drug holiday.

    • The longer you are on an anti-CD20 therapy the longer it takes for significant B-cell reconstitution to occur. It also depends on individuals; some start seeing reconstitution occurring at ~6 months others have to wait 18 months. Most people see it happening sometime between 9 and 12 months. In other words, you would have to miss a dose and have the vaccine close towards the end of the year, i.e. before the next dose is due.

        • Yes, some centres in the world are already adapting dosing based on B-cell levels. I think they are wrong because MS is not relapses and MRI activity, which is what they are basing their decisions on. The real MS is smouldering MS and it looks that you need higher doses of ocrelizumab to tackle this pathology. You have to go beyond being simply NEDA-2 (no relapses or MRI activity(, but target end-organ pathology. This is why we want to do a double-dose (Dodo) study to assess this hypothesis.

          • Prof G, could you clarify why you feel adaptive dosing based on b-cell levels is wrong? Has your opinion, or the data, changed since advocating for the ADIOS study back in 2019?

  • I’d love to know. As a pwMS treated with alemtuzumab in Sept, who’s also taking hydroxychloroquine I guess I might be more prone to being a spreader/shedder if I have had it. With hayfever/cough variant asthma and the ms hug coming and going, I worry I might not notice mild symptoms if my temperature doesn’t increase.
    There will be plenty like me who would love to know. There are certainly a few on the lemtrada group who have had positive tests and come through.
    Testing might go some way to mitigate the fear that some post-alemtuzumab pwMS have developed.

  • Me! I would want to know and I would want to be part of this study.
    Potential mild covid in March. Have had 2 halves and first full infusions. Next due in September and genuinely considering delaying due to vaccine reasons….

    Although as with the flu jab last year when I started on the DMT I was told – response to flu vaccine may be less but should still be there, so still have the jab and def start the DMT for MS control. So I wonder why this would be any different (apart from the fact covid19 is f&@!*ng terrifying of course)

  • But does it matter about vaccine response or antibody response if being on Ocrevus has some form of protective effect against severe illness with Covid-19? Will we just live with the risk of catching it and it being a mild/moderate illness that isn’t likely to kill us. Or is the risk more that we become carriers, and spreaders?

    Struggling to understand not be controversial. I read these columns avidly (and think them brilliant) trying to assess my risk – short & long term, as an NHS worker. Right now I’ve been sent a shielding letter (which has been inconsistently applied across the country and between trusts). But as a manager I can WFH.

    I don’t know if my infusion centre is going to delay my next dose (due next month)… if I want them too, or if, potentially ocrevus could dampen down the risk of a deadly cytokine storm if I catch covid-19 ( if I haven’t already) should I proactively push for no delay in dosing… confusing.
    Comorbidity wise I am listening, BMI >35, metabolic syndrome (pcos) – keto/low carb, vit d, zinc and a spirometer all purchased plus exercise increased where poss – unfortunately uhthoffs is long term sequalae of last big relapse in 2018.

    Do I care more about the lack of antibody response, blunted vaccine response when ocrevus might protect me from serious covid-19…what are implications for me as carrier/spreader. Does my other comorbidity neutralise any benefit Ocrevus might bring – should I change DMT if offered…but yet none so effective or suitable as ocrevus for me…it’s a head scratcher…keep doing what you are doing is all I ask and I will keep trying to figure it out 😊

    “Highly active” RRMS, 45f, edss 4 – on Ocrevus since June 2019.

  • Excellent points but if the CD20 counts begin to bounce back after 24 weeks (or so the theory goes) and hence the Q6 monthly dosing, but if OCR and RTX only blunt B cells carrying this ‘CD20 flag’, and do not affect the so-called plasma cells (some authors claim that plasma cells do not carry CD20 markers, some authors say they do so there is more confusion to go around), and supposedly the CD20 cell surface markers are missing from the hematopoietic stem cells, why would the Ab response be blunted ?

    Yeah, immunoglobulins take a dip when a patient is on RTX and OCR and I guess we base our hypotheses partly based on these findings and perhaps that is the reason why OCR and RTX would be at the bottom of the pile in terms of responses to vaccines ?

    As well, what are our cousins fighting the same battle but with drugs used in oncology or rheumatology doing to fight the SARS-CoV2 ? They are, and must be in worse shape ! What lessons can we learn from them , pray ?

  • Dear Prof G,

    I am a 22 year old who is diagnosed with CRION. I know this is more a MS blog but i think i am equally involved in this situation concerning my therapy. I get rituximab every 6 months and I just started the therapy in november 2019. Now in may/june i should get my second infusion.
    I just writing here, because the information in my country about immunosupressions and Covid-19 is not present. I was just told by my neurologist i am a high risk patient and I should not leave my house etc.. But as a 22 year old I am struggling now being 2 months at home and becoming a little hypochondric too.
    Hoe do u see me at risk now getting severe Covid-19? And should i start my second therapy now in order to be vaccinated next year?
    Regards

    • As a fellow lemtrada patient, please can I ask Laura from this morning’s post, am late catching up today, the reason why she is taking hydroxychloroquine? Am just curious – thanks in anticipation of reply.

  • I may be wrong but my understanding is that it is still very much unclear whether antibodies, including neutralizing antibodies, indeed confers immunity to covid-19. Also, in the unfortunate event there isn’t immunuty via antibodies, wouldn’t that have a significant negative effect on the efficacy of any vaccine?

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