CD20 and COVID-19

C

The CD20 onslaught continues at a pace and there is no refuting it, anti-CD20 depletion blocks the formation of vaccine response. I have seen this occur irrespective of the vaccine that was used. I am sorry to say if you are on anti-CD20 you are going to see this over and over again…it will be like-water torture, drip, drip, drip.

Yep and I control the tap (faucet for our American readers:-)….The water will continue to flow until our work surfaces and is done

CD20-depletion is used all over the place because it is good at stopping many disease responses…but in this context it is also good at stopping the formation of new antibody responses. We can see this in arthritis and MS and lupus etc etc etc.

There are about 200,000 people taking ocrelizumab (Ker Ching) and they should be vaccinated. We have only seen case reports from about 150 people so far and these are all for the Pfizer vaccinees, so stay turned for a lot of papers, and be prepared for the Astrazeneca vaccine data.

I predict it will be worse news antibody-wise. Why?

Because it is becoming very clear that the AZ vaccine induces a much lower antibody response than the RNA vaccines. You could always see this signal based on trial data but now that head to head studies have arrived it is obvious in my mind. Maybe this is because you spend your effort also making adenoviral antibodies or maybe because the vaccine makes a floppy Spike as the others are engineered to have a more rigid Spike (Furin cleavage sites removed). Moderna probably induces the strongest antibody response based on the trial and some real-life data.

The Americans have dodged this AZ bullet as this vaccine was never made available, and it is now being avoided in MS-endemic areas (Norther Europe) because of the blood clot issues. As booster season arrives in my mind, immunosuppressed people should be offered something else and the JCVI need a bit of a shake.

Fear-not if you had the AZ vaccine before, it is perfectly safe to get an RNA-vaccine as a booster and if may work better. There are plenty of papers surfacing on that one.

Can you say how much antibody you need to be protected? and I say “I don’t know”, but if you start with a very high level you will be protected for longer.

So what does this mean?

At the moment we have made the case that macrophages and T cells are pretty good at getting rid of the virus and you don’t need antibodies for this to occur because you can get rid of the virus before you make an antibody response and most B cell depleted individuals recover. However high levels of antibodies are probably going to stop infection,

However as the antibody levels drop you may get infected and show some signs of COVID-19 and then the T and antibody immune response will kick in. It means you may get disease but deal with it. Antibody levels often wane over time and this is why boosters are being considered. This will give your antibody levels a kick in the tush. It seems in immunosuppressed people with low antibody responses after two rounds, a third dose can make the difference. I think however that CD20-depletion is a different beast and the immunosuppressed people making a response are not taking anti-CD20 depletion. This is a special case and I hope the JVCI understand this.

If you are on immunomodulating treatment even if you make an antibody response it is probably at a lower level. This will wane quicker and if you are on an adenoviral vaccine the starting point for the waning response is lower, it will be quicker still….so I can see the Astrazeneca vaccine becoming a thing of the past for people taking immunosuppressive agents.

The next problem with a low antibody response are variants. We can see that antibodies against the Wuhan-variants work against alpha (UK variant) or delta (Indian variant) but to work effectively you need more antibody maybe three to ten times more antibody and so as the level of antibody drops you become more susceptible to the variants of interest e.g. delta. Given that BoJo and his chronies are inviting us in the England to a COVID-19 fest….free-for-all…with cases still massively increasing remember to be cautious, as you have been, if you are taking anti-CD20, you are likely to have a weak or non-existent antibody response.

However, what is becoming increasingly clear is that you make a T cell response after vaccination and so this should give protection. Will it stop you showing an infection maybe yes but for some I think not because you will not have the sufficient immunity. Will it inhibit hospitalization let’s hope so and if you end up in hospital let’s hope it stops you going to ICU. I have heard of double-vaccinated dosed ocrelizumabers getting infected. However, the only way to understand if the vaccine is making a difference is to look at big numbers and the only people to be able to do this in my mind, will be people with big registries like the Scandies have. The Aussies have MSbase but as they have been locking- themselves-in the infection rate is going to be so low, I will have retired by the time they get the data:-).

So the one big hope is …yes you’ve guess it…….Pharma.

The manufacturers have their pharmacovigilance process and so they can collect the data. They also have thousands of people in trials…..I know the makers of ocrelizumab are doing this and are best place to get the big picture. Sure some academics will do it, to ensure it is reported properly.

Can we optimize an antibody response for people on ocrelizumab, I think to some extent yes, but it will not be straight forward given the variability between people in their response to CD20 depletion. Remeber keeping MS at bay is a good protection against COVID as disability is an enemy. The manufactures will probably not investigate optimization if it strays away from the label recommendations. At the moment we do not have the information how best to do this and do not know if it is worthwhile and so the more CD20-antibody response data that we get, the better we can assess this. Also remember vaccination may be a regular occurence

So the new challenge for the global initiative and the MS Societies..Collect CD data

Note this is arthritis but it doesnt matter

Simon D, Tascilar K, Schmidt K, Manger B, Weckwerth L, Sokolova M, Bucci L, Fagni F, Manger K, Schuch F, Ronneberger M, Hueber A, Steffen U, Mielenz D, Herrmann M, Harrer T, Kleyer A, Krönke G, Schett G. Brief Report: Humoral and cellular immune responses to SARS-CoV-2 infection and vaccination in B cell depleted autoimmune patients.Arthritis Rheumatol. 2021 Jul 1. doi: 10.1002/art.41914. Online ahead of print.

Objective: B cell depletion is an established therapeutic principle in a wide range of autoimmune disease. However, B cells are also critical for inducing protective immunity after infection and vaccination. We therefore assessed humoral and cellular immune responses after infection with or vaccination against severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) in B cell depleted patients and B cell competent healthy controls.

Methods: Antibody (ELISA) and T cell (IFNγ ELISPOT) responses against the SARS-CoV-2 spike S1 and nucleocapsid proteins were assessed in a limited number of infected (N=6) and vaccinated (N=8) B cell depleted autoimmune patients as well as infected (N=30) and vaccinated (N=30) healthy controls.

Results: As expected, B and T cell responses to the nucleocapsid were observed only after infection, while respective responses to spike S1 were found both after infection and vaccination. A SARS-CoV-2 antibody response was observed in all vaccinated controls (30/30, 100%) but in none (0/8) of the vaccinated B-cell-depleted patients. In contrast, after SARS-CoV-2 infection, both B-cell-depleted patients (spike S: 5/6, 83%; nucleocapsid 3/6, 50%) and healthy controls (spike S: 28/30, 94%; nucleocapsid 28/30, 93%) developed antibodies. T cell responses against the spike S1 and nucleocapsid proteins were found in both infected and vaccinated B cell depleted subjects and in the controls.

Conclusion: These data show that B cell depletion completely blocks humoral but not T cell SARS-CoV-2 vaccination response. Furthermore, limited humoral immune responses are found in B cell depleted patients after SARS-CoV-2 infection.

However rememebr to stay safe, being vaccinated does not mean you are bullet-proof man and if you have been taking CD20-depleting antibodies and other treatment you have a more limited protection.

You can be vaccinated and get COVID-19.

Nissimov et al. BNT162b2 vaccine breakthrough: clinical characteristics of 152 fully-vaccinated hospitalized COVID-19 patients in Israel Clin DOI:https://doi.org/10.1016/j.cmi.2021.06.036. Microbiol infecthttps://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(21)00367-0/fulltext

A total of 152 patients who received the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine and developed COVID-19, requiring hospitalisation, more than 7 days after receiving the second vaccine dose. The median time elapsed from the second-dose vaccination to admission was 39.5 days (range 8-97), and the majority (82%) of patients were admitted 21 days or more after vaccination, which, noted the researchers, supported the assumption that the patients were not infected before vaccination. The median age was 71.1 (range 22-98) and most (70%) were males. The cohort was characterised by a high prevalence of comorbidities including hypertension (71%), diabetes (48%), congestive heart failure (CHF; 27%), chronic kidney diseases (24%) and chronic lung diseases (24%), dementia (19%), and cancer (24%), with only 6 (4%) patients having no comorbidities. Additionally, immunosuppression was present in 60 (40%) patients. Common causes of immunosuppression were chronic corticosteroid treatment, chemotherapy or anti-metabolite treatment and anti-CD20 treatment.

Good news from India

Clinical outcomes in vaccinated individuals hospitalized with Delta variant of SARS-CoV-2V, J. K., Sowpati, D. T., Munigela, A., Banu, S., Siva, A. B., Sasikala, M., Nutalapati, C., Kulkarni, A., Mukherjee, P., Zaveri, L., CCMB COVID-19 Team, , AIG Hospitals COVID-19 Vaccine study Team, , Tallapaka, K. B., D, N. R.10.1101/2021.07.13.21260417 

Emerging variants of SARS-CoV-2 with increased transmissibility or immune escape have been causing large outbreaks of COVID-19 infections across the world. As most of the vaccines currently in use have been derived from viral strains circulating in the early part of the pandemic, it becomes imperative to constantly assess the efficacy of these vaccines against emerging variants. In this hospital-based cohort study, we analysed clinical profiles and outcomes of 1161 COVID-19 hospitalized patients (vaccinated with COVISHIELD (ChAdOx1) or COVAXIN (BBV-152), n = 495 and unvaccinated n = 666) in Hyderabad, India between April 24th and May 31st 2021. Viral genome sequencing revealed that >90% of patients in both groups were harbouring the Delta variant (Pango lineage B.1.617.2) of SARS-CoV-2. Vaccinated individuals showed higher neutralizing antibodies (545+-1256 AU/ml Vs 51.1+-296 AU/ml; p<0.001) when compared to the unvaccinated group. Severity of the disease (3.2% Vs 7.2%; p=0.0039) and requirement of ventilatory support (2.8% Vs 5.9%; p=0.0154) were significantly low in the vaccinated group despite the fact that these individuals had significantly higher age and risk factors. The rate of mortality was about 50% lower (2/132=1.51%) in the completely vaccinated breakthrough infections although mortality in individuals who had received a single dose was similar to the unvaccinated group (9/269=3.35% vs 23/666= 3.45%). Our results demonstrate that both COVISHIELD and COVAXIN are effective in preventing disease severity and mortality against the Delta variant in completely vaccinated hospitalized patients.

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MouseDoctor

34 comments

  • Thank you very much for all the information re anti CD20 and vaccine response. Is there any information on alemtuzumab yet?

    • I have seen some and it is not all good, but it certainly is not bad, but I believe that there should be news arriving in a preprint very soon (next week or two)

  • EBV reactivation is being associated with long covid,

    Do you think this may have any implications for people with MS e.g more progression or attacks?

    And/or could there be benefits on the horizon regarding EBV treatments as more money maybe put into long covid research and treatments. If it does turn out to be EBV reactivation causing long covid.

    • Remember most people have EBV and so if it is important then it will affect us all the same no extra
      worry

      • I know most have it. But long covid is becoming a bigger issue and EBV is possibly causing it.

        Treatments for long covid could help people with MS if EBV is the target of the treatments.

        (That’s if anyone develops a treatment for long covid obviously)

  • Good Morning Mouse Doctor,

    In your last post, you mentioned that if we wanted to we could make a donation to your team. I would be interested in helping fund a trial just like the famciclovir one from the Crowdacure platform. In this case, I would be interested in donating for a trial of zidovudine from which we can see if it suppresses EBV in the not too distant future. It could potentially be posted on Kickstarter or Gofundme. I would love to help out with what I can to help move this treatment strategy forward. If this is something you are hesitating on you can always ask your audience ( on the MS Blog ) through a survey to see how many of us are interesting in financially supporting such a trial. I look forward to hearing from you.

    Kind regards

    • I have checked up with profK to see where we are on that , but to fund a trial you have to have deep pockets or had thousands of friends with shallower pockets..
      ProfG is crowd funding expert and has the interest in the anti-virals maybe he can have a think

      • Good evening Mouse Doctor,

        Before I begin, thank you for taking the time to respond. In the event that Prof G is interested in starting such a crowdfunding project, I would be delighted in helping out to fund this trial. What are Professor Gavin Giovannoni’s thoughts on starting a round 2 of a Crowdacure project ? I think we can achieve this just like the first time your team managed to get funding on Crowdacure. No need to give an answer right now but if this idea resonates with him let me know I will be the first to help financially support your teams idea with what I have.

        Kind Regards

  • Thanks for this update MD…..it always baffled me why cd20 patients were not offered the mRNA vaccine based on efficacy alone….I have just caught covid despite being double jabbed. I was gutter having being careful for 18 months, battled through the lockdowns with 2 young kids etc but given the case numbers this was probably inevitable anyway given my poor level of immunity. So, to my question…..will havinn and hopefully recovering from the virus now boost my protection against reinfection to a reasonable level? And what happens after my next infusion in August? Does that protection then suddenly wain

    • I would say when we started jabbing the UK it was known on the antibody hierarchy Moderna>Pfizer>>Astrazeneca….However there was no supply of pfizer until April started Jabbing.

      If you have had the virus it will bost your immune responses e.g. infection + 1 Jab = 2 jabs.

      The protection you have should wane

      • Thanks MD…wain over time or due to the next infusion? I’m seeing this as 2 jabs + infection = 2 + booster. Trying to be positive. Damn those euros

    • It was evident to me that moderna>pfizer>>Asrazeneca in terms of vaccine capacity to induce antibody response but there were no head to head studies allowing the pea counters to say we dont know. Vaccinations started in January and there was no supply of Pfizer until April and so we used what we had and lastly we di not know how bad the response was going to be remember the vaccine data indicated that most people made some response and lastly the trials sponsored by the Government in immunosuppressed people was loaded with people who were going to respond…Indeed I saw data yesterday claiming that 75% immunosuppressed people make a response. It is clear that anti-CD20 and mycophenylate, are in a differnt class the data I have seen so far ranges from 15-40% make a response.

      Now the other thisngthat is relevant to you is that if you have been infected and recovered you have a good enough immune response to get rid of it and in health previous infection + 1 Jab = 2 jabs there are about 50 papers on this.

      What happens after my next infusion: I suspect very little what immunity you have you should keep.

      Protection will wane with time, but when you get infected you deal with the infection and it goes quickly, this is the common cold type response, a sniffle and a sniffle for a few days followed by recovery unless of course it is a manflu:-)

  • Hi Mousedoctor,

    Thanks for the post. I really appreciate this blog and all its informations.
    As a patient myself (CRION) and being treated with RTX I just did my antibody testing after my second moderna dose. As expected negative. I am now planning to do an ELIspot-test on my t-cells.

    My question is now:
    Have you heard of the Covac-1 studies in Germany.
    That is a vaccine which is especally produced for people with lack of antibodies and are now in the clinical phase 3. The aim is to induce a strong T-cell response. Studies are made by the University of Thübingen.
    I just wondered what you think about it and I personally thought to participate in this study.

    Hopefully things will change for us..
    Stay strong anti CD-20😅

    • At the moment the data seems to show that people treated with anti-CD20 on the whole make a T cell response.
      I believe COVAC which was the Imperial College Approach was terminated a long time ago maybe I am wrong.

      Maybe the way to go would to give people an antibody response

      • I see the glas half full, therefore I am happy about this T-cell response.

        The study is ongoing, the papers are are mainly in german. Just found this link https://covid19.trackvaccines.org/vaccines/41/
        Currently in phase two. Estimated to be finished in october 2022.
        Furthermore the option with just a T-cell response wont be enough?
        Because delay of treatment and vaccination is not my favorite option.
        However, will it be the only one?

  • Excellent post thank you very much it says very much what I have picked up in the media although it is more condensed and clear in your post
    As someone with advanced MS I was totally relieved when I got the Pfizer because most people were getting the AstraZeneca so let’s hope everyone with MS whether on DMT or not get a booster of Pfizer or Moderna
    Is it right that there have been reported cases of guillain-barre following the Johnson and Johnson vaccination?

    • Covid-19: Regulators warn that rare Guillain-Barre cases may link to J&J and AstraZeneca vaccines.
      Dyer O. BMJ. 2021 Jul 14;374:n1786. doi: 10.1136/bmj.n1786.

  • Sometimes I really marvel at my ‘luck’ in not only developing MS, but then choosing a DMT just pre a major worldwide pandemic that not only immunosuppresses me, but also is the ONE treatment that makes the vaccine almost useless.

    Sigh!!

    Oh and I work in healthcare too….doh!

    Although, despite all of this I do feel a glass half full attitude as I am thrilled that the T cell response has been proven. And also I had antibodies after my vaccine and am <40 female with no co-morbidities. I have to grasp at these straws!

    I must say the UK is a scary place to live and work in right now though

    • ONe treatment….fingolimod is abit worse according to Israeli data:-(, but better news from south America.

      Also I had antibodies”…so there you go….in MS responders Pfizer + anti-CD20 = Astrazeneca healthy control. Fill your glass abit more
      Less than 40, female, no co-morbidities ….catch covid….No sweat. + vaccination = sweat less or is it gently go (Horses sweat, men perspire and women gently glow)

  • Hey MD. I have a rookie question.

    In short, do T-cell responses also provide immune system ”memory”?
    For instance: will an otherwise healthy individual treated with anti-cd20 who had a T-cell response but no B-cell/antibody response to the vaccine still be likely to have a more efficient immunereponse in the event of covid exposure?

    • Yes, you get T memory cells too. You’ll get a response but it won’t be as complete as if you had a full complement of B cells but a T cell response is certainly better than nothing and should be protective to some degree.

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