Whilst CD20 antibody will probably blunt your anti-COVID19 antibody response. Probably fear not as remember T cells are the important ones. #MSCOVID19

W

In a rush go to the bottom to read

T cells are the important ones. What? Am I having a bit of psychosis?

I have been on a B cell crusade and have been saying that B cells are important for MS. ut now its T cells are important.

Well yes and Yes.

Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis.Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K.EBioMedicine. 2017 Feb;16:41-50. doi: 10.1016/j.ebiom.2017.01.042. 

These this suggests that B cells are important target in MS and this is why ocrelizumab is active.

However for COVID-19 we changed our tune and said it is the macrophages that are the important ones and that you can get rid of the virus before you make an antibody response.

The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.Baker D, Amor S, Kang AS, Schmierer K, Giovannoni G.Mult Scler Relat Disord. 2020 Aug;43:102174

The prediction was that most people on DMT would recovery from SARS-COV-2 infection and that ocrelizumab may have issues when it comes to making a COVID-19 response. We asked are you vaccine ready and predicted that their could be problems for ocrelizumab and rituximab and other anti-CD20 antibodies.

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases.Baker D, Roberts CAK, Pryce G, Kang AS, Marta M, Reyes S, Schmierer K, Giovannoni G, Amor S.Clin Exp Immunol. 2020 ;202(2):149-161.

We suggested that if you were going to stop taking anti-CD20 in response to suggestions from Neurologists, that because the memory B cells are depleted in most people for well over a year that a few months delay may not be a worry. We also suggested if that you were going to stop taking ant-CD20 to allow the B cells to return then you would have to wait a very long time as it takes a median of 60-70 weeks for the CD19 B cells to reach the lwer limit of normal. Ofatumumab repopulates quicker but it still takes 40 weeks to repopulate the CD19 B cells. Therefore it does make sense to stop taking it for that long. Now it is more likely that if you wait towards the end of the cycle that you will maximise you chance of making and antibody to the vaccine, the advice was to take the vaccine if offered.

We also predited that ocrelizumab would blunt the vaccine response to COVID-19 virus. and this was susbsequently seen with ocrelizumb and rituximab.

This was further shown recently

Wallach AI, Picone MA. The presence of SARS-CoV2 antibodies in MS patients. Mult Scler Relat Disord. 2021;50:102793. doi: 10.1016/j.msard.2021.102793. 

Background: The COVID-19 pandemic has raised novel concerns for people living with MS regarding their safety.

Methods: Observational study of patients at a single comprehensive community MS center.

Results: 48 patients with MS were suspected of developing COVID-19 March to May 2020;. Of the remainder, 17 were tested for COVID-19 antibodies as part of routine care. Average age of this subgroup was 49.8y ± 11.3 (age range 32-67), 76% female. 65% were treated with an anti-CD20 drug, 12% untreated, and 6% each received glatiramer acetate, interferon, natalizumab, or teriflunomide. 59% of patients were antibody negative.

Conclusions: The low incidence of SARS CoV2 antibodies following infection suggests that certain DMTs may alter SARS CoV2-Ab response or persistence.

This one slipped under my radar. But looks at the occurrence of COVID-19 and the production of anti-COD-19 virus. In ths study 48 people were followed .

65% of patients (n=11) were treated with an anti-CD20 monoclonal Ab (10 ocrelizumab (OCR); 1 rituximab (RTX)), 12% (n=2) were untreated, and 6% each were on treatment with: glatiramer acetate, interferon, natalizumab, or teriflunomide. Only 41% of patients (n=7) were antibody positive.

So the antibody response is blunted, maybe you make one but is doesn’t last long.

However, the resason why it is not worth delaying you COVID vaccination for a year whilst your B cells go back to normals, because based on our early studies we suggested that T cells were important.

CD8 T cells are generated by all current vaccines that are approved in UK/EMA/USA

We will have to wait and see and hopefully vaccination of people treated with ocrelizumab will not devlop COVID-19 and if they do it should be a mild disease course.

In support of this we can turn to cancer for some insight.

CD8 T cells compensate for impaired humoral immunity in COVID19 patients with hematologic cancer.Huang A et al. J.Res Sq. 2021 Feb 2:rs.3.rs-162289. doi: 10.21203/rs.3.rs-162289/v1.

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19). In a cohort of 100 cancer patients hospitalized (remember most people with MS will not be hospitalised) for COVID-19 at the University of Pennsylvania Health System, we found that patients with haematologic cancers (white blood cell cancers like leukemia and lmphoma) had a significantly higher mortality relative to patients with solid cancers (tumours) after accounting for confounders. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19, whereas patients with haematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. (We feared that cancer is a risk factor for more severe COVID-19 and is a reason people with cancer have been asked to shield ). An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients (MS relevance: HSCT and alemtuzumab are the two agents depleting CD8 T cells the most. HSCT use has been limited because of this percieved risk. Ocrelizumab has minimal impact on them. Dimethyl fumarate can deplete CD8 Tells also) In contrast, despite impaired B cell responses, patients with haematologic cancers and preserved CD8 T cells had a lower viral load and mortality (MS relevant this is most like ocrelizumab, rituximab and cladribine that has a modest impact on CD8 Tcells) . These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity.

Now the important Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other haematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with haematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.

Therefore suggesting that despite a limited vaccine B cell response a vaccine induced T cell response (aided by your macrophages are going to be key in protecting you when you have vaccination.

About the author

MouseDoctor

17 comments

  • Very interesting thank you.

    Am I right in thinking these studies are related to antibody production (or not) following covid infection, and not following vaccination?

    Am I naive to think the results following vaccination may be better?

    • The antibody levels following vaccination are probably going to be higher than with the natural infection. We will see an avalanche of paper of ocrelizumba inhibiting the vaccine antibody response. However we will not know what it means as we dont know how much antibody is needed to give protection

      • Yes I wondered if this was a warning shot that there are going to be a lot of papers and results showing a blunted response.

        Sigh!

      • Are you sure about antibodies being higher after vaccination compared to natural infection? This could be the case for patients with mild symptoms, but for severely ill patients the titers that we find are incredibly high, far beyond what we see with any common vaccine. Btw we are testing this as we speak for the Pfizer vaccine, so we’ll be able to give you an update on this soon.

        • Most people with natural infection produce no or low titre antibody response if they are asymptomatic or had mild infection there are hundreds of papers on this. As for severely ill people
          you are are part correct. However we already know the answer. Look at the phase I studies as they compare to convalenscent i.e. severely ill people serum. With the Astrazeneca vaccines they are about the same, but with the RNA vaccines (Moderna and Pfizer) they appear to be higher than convalescent sera, obviously there will be over lap. If you want to see vaccine responses in general use this has already been reported on MedRXiv about 2-3 weeks ago, so get cracking as there will e ten groups doing the same thing.

  • Personal experience: I’m on ocrelizumab, and had a dose recently, so my fear was CoVID-19 vaccine wouldn’t do much. I had the Pfizer vaccine and initially no reaction and I hardly felt it go in. The next day, achy arm at the injection site. Day 3-7 aching all over. Brilliant – something happened. I’ve never been so pleased to experience pain. Must have been the T cells.

    • Thanks for sharing @Mark. Ditto here! Only difference is I am a bit ahead of where you are – I had my second jab a week ago (Pfizer). I felt perfectly fine first day, then days 2-6, achey all over & didn’t feel up to much exercise. Today is day 7 & I feel so much better.
      Go T cells Go!

    • Also on ocrelizumab, was due for next round this month but that has been postponed pending vaccination. I had the first dose a couple of weeks ago – Astra-Zeneca in my case. Initially felt fine, but woke up aching all over and unable to move any limbs at 4am the night after. Migraine and arm/leg/back aches for the following 24 hrs, but subsided into a mild arm ache for the next few days. Dreading the 2nd dose now, if it’s likely to be worse…

  • Same here. I’m on Rituxan, have low IgG and low enough to need to receive monthly IVIG infusions. Got the first Pfizer dose and I had a headache the rest of that day. 3 weeks later I received the second dose, had headache again. About 10 hours later I had the chills and the feeling of a fever and went to bed. The next day just felt generally unwell, plus muscle aches and all of those symptoms from the day before continued. The day after that, back to 100%. I was so happy to have had a reaction.

  • Oh and also my last Rituxan round was only a month before that first dose (early December). I really didn’t expect to be able to get the vaccine for months but luckily had the opportunity and took it. I would have postponed Rituxan if I knew! Maybe a new booster for the new variants will come in time before the next Rituxan dose..

    • Yes we know about antibodies worsening disease you can read obout this in our reviews published long before these papers ever appeared, it is all part of immunology 101 and as we know convalescent sera has had mixed results and have generally failed…all you have to do is read the literature and the history. (e.g RSV and dengue vaccinations) If you want an anti-viral you want the high titres to stop infection, this is what vaccination aims to do) because once the cells are infected if you use your immune system to get rid of the infection you get damage…massive infection massive damage…Simples. We have not learned this and that is why we have so few effective treatments…they should have been used when first infected not 10-20 days later when people are hospitalised it is too late.

      The monoclonal antibodies being made against covid are not approved for hosptialised use for the reason that they can cause problems, they are licenced for infection prior to hospitalization, they should have been used as a prophylactivc e.g. Docotrs on the front line to stop them getting infected or perhaps people on ocrelizumab who make not make a high level of antibody response. Roche makes both antibodies and could have done this, but they wouldn’t because to do so who suggest there was a problem…Rule nuber one of Pharma club…don’t find problems with your drugs

      • Haha, rule number one of the Pharma club :-).
        Yet, i don’t think the previous ideas about how antibodies worsen the pathology in e.g. Dengue (ADI, i.e. enhanced infection) are applicable to SARS-CoV-2, very little evidence for that. In severe COVID-19, antibodies amplify inflammation, not infection (very different mechanism).
        Btw it’s pretty easy to make antibodies that only neutralize but do not have any effector function (“Fc dead”), they shouldn’t cause any damage (but on the other hand, you probably won’t get rid of your infected cells either…).

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives