Booster.. Not good news for anti-CD20..Time to get thinking caps on quickly because the same old same old is probably not going to be good enough.


We can learn from other conditions and if they are seeing the same thing to MS they are more likely to be true. Here is a view on arthritis

Fagni F, Simon D, Tascilar K, Schoenau V, Sticherling M, Neurath MF, Schett G. COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses. Lancet Rheumatol. 2021 Aug 27. doi: 10.1016/S2665-9913(21)00247-2. 

At the beginning of the COVID-19 pandemic, patients with immune-mediated inflammatory diseases were considered to be at high risk for SARS-CoV-2 infection and the development of severe COVID-19. Data collected over the past year, however, suggest that a diagnosis of inflammatory arthritis, psoriasis, or inflammatory bowel diseases does not increase risk for SARS-CoV-2 infection or severe COVID-19 compared with people without these diseases. ………………….., glucocorticoids and potentially B-cell-depleting treatments seem to worsen COVID-19 outcomes. Additionally, the first data on SARS-CoV-2 vaccination in patients with these diseases suggest that tolerability of vaccination in patients with immune-mediated inflammatory diseases is good, although the immune response to vaccination can be somewhat reduced in this patient group, particularly those taking………….CD20-targeted treatment.

Does it sound familiar…Sure it does

However information is rapidly appearing and some info is out of data before it arrives

Wolf A, Alvarez E. COVID-19 Vaccination in Patients With Multiple Sclerosis on Disease-Modifying Therapy. Neurol Clin Pract. 2021 Aug;11(4):358-361.

Advice =To maximize the immunologic response, it is suggested by the Canadian Network of MS Clinics (……For patients already on anti-CD20 DMT, waiting 12 weeks (as in the VELOCE study) after infusion to start the vaccination process is recommended.

This is not a magic solution and many people will not respond to vaccine using this approach and in fact most won’t.

It has also been proposed to delay vaccination until B-cell reconstitution or toward the end of an infusion cycle, but the risks of contracting COVID-19 need to be considered.

Good idea but one problem the dosing schedule is designed to remove B cells permenently so most people will not repopulate. Likewise to delay takes you outside of the protection of the label So will it be done.

The label says “In the Phase III studies, between each dose of Ocrevus, up to 5% of patients showed B-cell repletion
(> lower limit of normal (LLN) or baseline) at least at one time point. The extent and duration of
B-cell depletion was consistent in the PPMS and RMS trials.” In the phase II trials less than 5% of people had 1% B cells at 9 months 50% at 12 months 85-95%

So without a delay between infusion and vaccine, I think that many people are unlikely to respond. However this needs discussion

Now to learn from cancer and B cell cancers

Lee M. Greenberger, Larry A. Saltzman, Jonathon W. Senefeld, Patrick W. Johnson,
Louis J. DeGennaro, Gwen L. Nichols Anti-spike antibody response to SARS-CoV-2 booster vaccination in patients with B cell-derived hematologic malignancies Cancer cell DOI:

Among the 21 patients who completed therapy with anti-CD20 antibodies………12 patients were non-responders, 7 patients demonstrated seroconversion, and 2 patients demonstrated sero-elevation. Notably, 5 of the 7 patients who completed therapy with anti-CD20 antibodies ………….at least 7 months prior to the booster vaccination demonstrated seroconversion………………In contrast, many of the patients who recently had, or are maintained on, anti-CD20 antibody therapy prior to booster vaccination failed to seroconvert after booster vaccination. It has previously been reported that recovery of B cells begins 6–9 months after rituximab therapy (McLaughlin et al., 1998). Thus, these data suggest that recent treatment regimens containing anti-CD20 antibodiesmay suppress the response to booster vaccination.

The new Iron maiden song asks “Have you seen the writing on the wall”….

I think I have and the writing gets bigger and bigger. Will we push on through the wall and what happens if we do?

So more MS vaccine news

Ali A, Dwyer D, Wu Q, Wang Q, Dowling CA, Fox DA, Khanna D, Poland GA, Mao-Draayer Y. Characterization of humoral response to COVID mRNA vaccines in multiple sclerosis patients on disease modifying therapies. Vaccine. 2021 Sep 2:S0264-410X(21)01126-9.

Little is known about COVID-19 mRNA vaccine humoral immune responses in patients with central nervous system autoimmune demyelinating diseases, multiple sclerosis (MS) and neuromyelitis optica (NMO), who are on B-cell depleting therapies (BCDT) and other disease modifying therapies (DMTs). We conducted a single center prospective study to identify the clinical and immunological features associated with vaccine-induced antibody response in 53 participants before and after COVID-19 mRNA vaccination. This is the first report (another first) on the anti-spike RBD and anti-nucleocapsid antibody response, along with pre- and post-vaccine absolute lymphocyte counts (ALC) and flow cytometry analysis of CD19 and CD20 lymphocytes in patients with MS and NMO. We tested the hypothesis that patients on BCDT may have impaired COVID-19 vaccine humoral responses. Among patients on BCDT, 36.4% demonstrated a positive antibody response to spike RBD, in comparison to 100% in all other groups such as healthy controls, untreated MS, and patients on non-B cell depleting DMTs (p < 0.0001). Immunological data revealed lower baseline (pre-vaccination) levels of IgM in patients on BCDT (p = 0.003). Low CD19 and CD20 counts and a shorter interval from the last B cell depleting therapy infusion to the first vaccine dose were associated with a negative spike RBD antibody response (non-seroconverter) in patients on BCDT. Age, body mass index (BMI) and total treatment duration did not differ between seroconverters and non-seroconverters.

Hope the Writing on the wall is getting bigger for you too?

However, we are not looking in the right direction for the major problem when it comes to vaccination.

The JCVI (Jonit Commitee of Vaccinations and Immunity) needs to get its thinking cap on

Remember I’m a scientist and dont have to think about clinical issues

Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.

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  • Better reactive measures?

    Anti virals? Access to Antibodies? Testing as soon as feeling unwell? Hydroxychloroquine?

    Proactive measures other than the jabs?

    Lose weight if needed? Eat real foods? Up Vitamin D levels? Ensure hygiene levels

    The jabs work obviously, however people on anti CD20 surely needs other advice and angles to fight covid should they get covid-19. The jab isn’t the absolute holy grail, other things can be done to help fight it.

    • Hydroxychloroquine has fallen by the wayside I think.

      Yes you are right other things can be done and losing weight is good advice…but what do you say to the mums and dads of young children who are spending their time infecting others?

      • “Young children their time infecting others”

        You mean by kids just living their lives and being kids?

        Well vaccinating kids isn’t going to stop the spread, people are always going to catch viruses, so people who are high risk should take pro cautions and do what they can themselves. Finding ways to treat covid after catching its need to be found as im sure they will be, if vaccine responses are poor.

    • As for proactive, I wish azd7442 was approved… Reactive there’s the other mabs (Roche should offer Ronapreve in a package with ocrevus :-)) but ideally you need to get them early and I really do not want sticks stuffed up my nose every few days…

      • I dont want sticks up my nose every few days…….we are asked to do this out of courtesy for our students and fellow workers twice a week.

        Roche is a dose every month

        • Which is why I want azd7442 which should last 6-12 months… That would likely tide me over until b cell reconstitute and then one can reconsider if moving away from anti cd20 is the right choice…

          Testing for the sake of other I will skip because a) I am by far the most at risk person everywhere I go (which is very few places) and b) they anyway largely don’t give a damn.

  • More of a general question regarding the covid vaccinations
    Are there plans to test people to see whether they have responded to the vaccine ? If they are one of the people who the vaccination has not worked on anyway this would then avoid constant pointless vaccinations or give you opportunity to try one of the the different type of covid vaccine
    Also if it has worked it gives you that little bit more confidence to go out.

    • Plans to test….I doubt it, if you have a response you booost it, if you dont you hope you conveert. Even if have a vaccine response it wanes with time and the high level of antibodies is what gives the maximal protection.

      If you had AZ vaccine it gives a weaker antibody response, the plan is to switch people to RNA vaccines. However I seee the maker of the AZ vaccine suggests we dont do to many boosters, so that we can vaccinate the World….I suspect most places cant give AZ away…in my mind booster the boosters should ideally be RNA vaccines…but Im not the JCVI

      • Mix and match studies are ongoing. Boost AZ with MRNA shows good antibody response I believe. There may be a place for MRNA to be boosted with AZ or others (what ever happened to Novovax? – production issues I’ve read) but are waiting for the data.

        As an aside, Prof. G in his recent newsletter also suggests anti-cd20 is a problem in covid era. He also suggests Mu variant will become dominant and prolong pandemic (in my view will be long amyway). However, many, many other experts think Delta will def outcompete Mu due to its transmissibility.

        • Novavax seems to have sorted out production issues. Should be available in next 8-ish weeks is what I am hearing.
          AZ response doesn’t seem to drop off as fast as Pfizer, so boosters may be unnecessary anyway.
          At the moment at least in areas where both Mu and delta exist, Mu doesn’t seem to be out competing delta.

      • I also heard last week that the boosters will be a combination of both Pfizer and AstraZeneca probably because pfizer is going to be used on younger people leaving a deficit for the older and more vulnerable people who had vaccinations originally.

  • Regrettably waiting 12 weeks from last infusion did not help mount an antibody vax response. T cell? One can only hope. Wait for B cell repop? A long slog. Wonder if there is a safe method to hasten that?

    • 12 weeks from last infusion is 3 months….you have no B cells at that point at 6 months only 5% of people have 1% B cells based on phase III data (own analysis) at 9 months about 50% and 12 months about 90%

  • I had y2 m1 cladribine in April 21
    I’d had Pfizer vaccines in January and End February 2021
    Had blood tests in July 2021
    Lymphocytes down to 0.25 but neuro ok with that (no anti virals etc)
    However also had covid antibody test st same time:

    SARS-CoV2-S Antibodies Quantitative
    Your Value
    2,256.0 U/mL

    I was concerned that vax was 6 months in past and whether cladribine had ‘blunted’ antibody response

    Ok so I’m told this is a good antibody response as a ‘good’ response typically around 2500?
    Neuro happy with antibody response

    Question – as antibodies are relatively high (are they?) do I wait until lymphocytes say around 0.8 before booster? If I get booster nowish my lymphocytes might still be low

    But I guess my covid antibodies will drop so I want to take booster at some point

    – at end of day feel lucky to have a good timing – or have I?

    • If you search the blog, you will find data from Israel that shows cladribine has very little effect on the vaccine response (as good as control response), at least for the Pfizer vaccine, shouldn’t have any effect on a booster response either.

      • There is a delay in israeli data of 4.5 onwards….I would not go straight after the second month…give it some time for cells to recover

    • The lymphocytes are low because of T cells abd memory B cells etc maybe not the cells making antibody response……..If you have a high antibody response you could wait until the response wanes and then give a top up.

  • So here’s a question – 78% of people in hospital with covid are over weight or obese.

    Should people who are overweight be stopped going into venues?

    If people who don’t have 2 jabs can’t go in to venue, when people who are over weight are causing more of a burden on the NHS can go in?

    It’s not controversial it’s factual, it wouldn’t happen as it’s controversial and discriminatory however true it may be, people would rather see health services collapse and struggle than talk about facts

    • But where someone either smokes (addiction), drinks excessive alcohol ( addiction) , overweight (addiction) – can you not differentiate that from someone who refuses vaccine (choice)

      No one chooses to be overweight- they make ill informed choices – But no one would ever choose to be overweight- but people DO choose not to get a vaccine – isn’t that the difference?

      • Thank you for arguing my point, those people are the burden not the unvaccinated who don’t fall into that bracket.

        I’m not anti vaccine btw, vaccines are the reason a lot of us are here today, it’s just people like to brush real issues under the carpet

        Our Government are happy to sell cigarettes, alcohol, junk food. And make money from that though tax, however unvaccinated are the issue, when there clearly not the only issue

        My point is people don’t want todo anything for themselves to help fight covid, but someone who does gets put in the, and to add to that there’s very little being put out their to the public’s to help them lower their risk of severe covid, when the discussion was what can be done.

        Good to see this morning a U turn on covid passports.

        • But isn’t insisting on people having jabs also about them not passing it to other people – which it does to some extent?

          The issue of being a burden on the NHS is perhaps a different although related issue?

          Saying that, when I was last in A and E, there was a football player in front of me with a crock leg GRRRR!

      • So if you choose to drink, smoke and eat you have to accept the consequences if you choose not to vaccine you shouldn’t?:-)

    • Interesting point ….(Life sucks right:-). As someone overweight it would have done me a favour if I had been stopped from seeing Royal Blood in Hastings….any one over 5 and half feet could not sit in the chairs as they were too close together. However, if I sit next to someone thin…this won’t make them fat….it is not infectious. Likewise if I am old it does not prematurely age you. Fatnness is self inflicted. On the other hand if I go into a venue infected then it impacts on others. Being double vaccinated does not stop you producing virus so I would say people should self test and then do the right thing if infected. As someone overweight I view everyone as a potential cause for my demise.

      So there we go……Stop the oldies going to venues too….I guess in some cases it is self selecting as they think the music of the youngsters is SH1, stop people on anti-CD20 going to venues, where do you stop. Maybe we should start to euthanase people when they are 30 so they dont take any NHS resource. Watch Lognas Run if you havent seen.

      If you work in NHS human samples you have to be hepatitis vaccinated, whats the is being part of that Society.

      • Exactly the reason unvaccinated shouldn’t demonised as the cause for overwhelming the NHS.

        Do unvaccinated people put more of a burden on the NHS and services than people who eat junk, lazy, smoke, drink excessively, abuse their body, persue high risk activities etc

        If the vaccine stopped the spread I would totally under stand however there’s no mention of other reasons for the overwhelmed NHS nor is there any good advise to mitigate the risk of severe covid 19, such as simply supplementing with vitamin D would be an easy simple one with zero effort.

        Seams like unvaccinated are to blame for the bigger issues

          • Great article, that’s the information people not to bash people who don’t get a jab, encourage them and educate from both sides.

            This is what the general public need more of, 95% of people won’t help themsleves or even give this advise to people around them.

            We need to protect the NHS, however bashing the unvaccinated isn’t the right approach, potentially alienating them from society isn’t the answer.

            Imagine taking care of your health in general and being told by an obese smoking shop owner who’s had 2 jabs that you can enter there shop as you’ve had one or no jabs, or a pub owner saying you can’t enter their pub.

            People are going blind to facts, my point is we’ve got to be careful not to segregate people it’s simply not the answer.

  • At this point should people on anti-cd20 just get regular doses of regeneron antibodies? We need a solution that’s different from vaccines sounds like

  • My understanding (from learning on this blog) is that the Regeneron monoclonal antibody cocktail is effective but not necessarily practical to use as a long term prophylaxis due to a relatively quick waning. However, albeit not currently useful, there is a pre-print discussing a new monoclonal antibody that if proved to work in a clinical trial may last for 12 months. Unfortunately (yet necessary) we need to wait for the trials….

    MD what is the solution in your opinion? Perhaps not at liberty to say.

  • I’m interested in finding out when this booster might happen. My GP surgery said not through them. The hospital team thought not arranged via them. My GP records I have access to via the app don’t appear to show I take ocrelizumab. So hopefully it’ll be flagged up by one of them?

    In better news, I did delay my last dose by a couple of months to get the jabs in first (jan/feb) and I just had my antibodies tested via the gov service as I take part in the Zoe study. That came back as positive for antibodies which was somewhat of a relief after all the news on here! Although no actual levels so hopefully enough to be effective and definitely better than none. I can go swimming indoors feeling much happier 🙂

  • A little late here, but,…what a mess. (I said 5 months ago something like this would happen.) Psychology needs a new diagnostic criteria- “MSARS-CoV-2”, or “mental covid”, for short. It is a combination of factors including belief of protection by a supernatural power, combined with degrees of ignorance and stubbornness, strict adherence to a specific philosophy of life, and a little bit of knowledge (as in “a little knowledge is a dangerous thing”). 97% of those dieing from covid infection, here now in PA USA, initially suffered from Mental Covid. Those who took the vaccine and were not otherwise immunocompromised never suffered from Mental Covid to begin with. I think the choice is very clear.

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