#MSCOVID19: COVAX or Coronavirus Ocrelizumab Vaccination Study

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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?

Baker et al. COVID-19 vaccine-readiness for ocrelizumab and other anti-CD20-depleting therapies in multiple sclerosis and other autoimmune diseases. Authorea. June 23, 2020. DOI: 10.22541/au.159292858.82650822

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.

CoI: multiple

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.

26 comments

  • Good morning,

    I am being treated with Ocrelizumab and will receive my next round of treatment on 13th July. I am treated by the team at Queens Square, but would be happy to participate in the COVAX study if you are able to include patients from hospitals other than Barts. I live in central London so access is not an issue.
    Please could you let me know how to register for your study should it go ahead.

    • We can only run this study when the vaccine becomes available. At the moment it is just a concept on paper and will need to be fleshed out to see if it is doable.

      • Hi,
        I realised that about 5 minutes after I posted. Good old cog-fog, I am endlessly functioning several minutes – sometimes days behind the rest of the world.
        My interested still stands I and will await further developments.

  • That’s an important issue bringing uncertainty to pwMS.
    In your opinion what should be the minimum level of CD-4 and CD-8 in blood flow ?
    Is 500 the minimum linfocite count to get vacinated?

  • I’d volunteer as well.

    By the way – typo on the last line – you refer to SARS-CoV-29.
    It’s SARS-CoV-2.
    Or Covid-19 (for the disease caused by the virus).
    “Lockdown brain” is a thing 😉

  • For women who are thinking of having a child, might it be best to try and time your drug holiday with Covid vaccine and pregnancy all in one? 2 birds 1 stone?

  • Hey,

    Wouldn’t this all be a non issue if we received Plasma from people who already had the infection? Are there any concerns with receiving Plasma or is it that we don’t have enough supply or a different reason?

  • I would sign up for this study.

    Btw could you please keep us up to date with covid vaccine developments as I find it difficult trying to summarise what I read from different news websites. Would be good to have this blog to refer to as it is important to us pwMS… just some news when there is actual news or developments w the vaccine would be great.

  • Do patients on anti CD20+ therapy show diminished antibody responses even with existing memory B cells or is it just difficult to establish new immunity upon vaccination? I hope this makes sense.

  • I would happily sign up.
    My first full dose was postponed from April. Pencilled in for 14th July.
    I had my bloods done today in readiness.
    I had an antibody test at my local pharmacy, which was positive.
    I was unwell late December to February.
    I guess this was actually covid.
    Regards
    Clare

    • That’s encouraging that you’ve antibodies despite ocrelizumab 👍 and that you managed to fight COVID ☺️
      I’ve had an antibody test at work as NHS staff (had it with pre ocrelizumab bloods) Haven’t heard so assume negative but thought I would be as shielding since March and no obvious COVID symptoms.

      • I had my two half doses in October. It was my first full dose that was postponed. Was so pleased when the result came back as I really thought if I got Covid I would be seriously ill due to being on Ocrevus.

  • Hello, I would like to participate. Where can I find more information?
    Scrolled down for some updates 🙂
    I am in Austin TX but pls keep me on a list. Thanks!

  • This was from an earlier post on DMTs and vaccinations:
    “Surprisingly, antibody response to common vaccines occur on anti-CD20 therapies, but antibody response to glycoprotein vaccines, for example, the pneumococcal vaccine are blunted or inhibited the most. This may be particularly relevant to a SARS-CoV-2 vaccine that is likely to require antibodies to glycoprotein antigens to generate neutralizing antibodies”

    I was curious as to some of the science as to why anti-CD20 antibody response would be less with the glycoprotein vaccination

  • Maybe b cell and antibodies are not that important in clearing sars cov 2

    Abstract

    Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus

    Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion

    https://www.medrxiv.org/content/10.1101/2020.06.21.20132449v1

  • Hi I would happily take part in the trial I am having my 8th infusion on the 9th July …..I was part of the trial for ocrelizumab at Kings college hospital.

    Please do keep me informed when there is further information.

    Kind regards

    Stay safe 🙂

  • I would if I was on Ocrevus. I had Lemtrada (round 2 in Jan 2017) so I obviously would not qualify. But kinda wish I did because I think this is important!

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