The deluge appearing #MSCOVID19 More evidence for CD8 T cell response in people treated with anti-CD20

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Drip Drip Drip its coming as the rain arrives so are those B cell papers

I recently saw a colleague who was concerned about whether it was OK to cite a pre-print because it was not peer-reviewed….However this is the new norm and in reality you can review it yourself. Also some reviewed papers are not without issues.

You have to determine whether you want to live under a “knowledge rock” for 6-9 months whilst the publication process unfolded or do you want to learn. Now the other important thing that COVID-19 has meant is that any paper that is published soon gets replicated or refuted.

So this paper says “the question remains as whether B-cell depleted patients could still mount a functional T cell response to COVID-19 vaccines, which may provide some level of protection against severe disease”

Natacha et al. medRxiv 2021.07.21.21260928; doi: https://doi.org/10.1101/2021.07.21.21260928

All we have to say to the referees of this one is read the paper already saying the same thing…Yes you do make a T cell reponse and it appears to the case that there is a stronger CD8 response in people who have a weak B cell response

Likewise you can ask do you need to do massive studies….I think alot of small studies saying the same thing add to likihood of a real.

Again we hear “antibody levels in patients correlated with level of circulating CD19+ B cells (measured at day 30 after
vaccination

Correlation of B cell levels and antibody response

So as you can see every one with a 1% CD19+ count made an antibody response of some level, suggesting that if you have this level at the time of vaccination and perhaps boosts then you make an antibody response.

You can see most people made an antibody response but some of there were very low

Sadly they did not give the time window of infusion to vaccine, maybe we have to assume it was 6 monthly)

Madelon N et al. Patients treated with anti-CD20 therapy can mount robust T cell responses
2 to mRNA-based COVID-19 vaccines. medRxiv preprint doi: https://doi.org/10.1101/2021.07.21.21260928

Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. This study assesses humoral and T-cell responses to mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8+ T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). Vaccine-specific CD4+ and CD8+ T cells were polyfunctional but expressed more IL-2 in patients than in controls. In summary, our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the prevention of severe COVID-19.

This view of the B cell levels being a biomarker of antibody response is evident in rheumatoid arthritis

Stefanski et al. B cell numbers predict humoral and cellular response upon SARS-CoV-2 vaccination among patients treated with rituximab. MedRxiv doi: https://doi.org/10.1101/2021.07.19.21260803

Objectives Patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) therapy show substantially impaired anti-SARS-CoV-2 vaccine humoral but partly inducible cellular immune responses. However, the complex relationship between antigen-specific B and T cells and the level of B cell repopulation necessary to achieve anti-vaccine responses remain largely unknown.

Methods Antibody responses to SARS-CoV-2 vaccines and induction of antigen-specific B and CD4/CD8 T cell subsets were studied in 19 rheumatoid arthritis (RA) and ANCA-associated vasculitis (AAV) patients receiving RTX, 12 RA patients on other therapies and 30 healthy controls after SARS-CoV-2 vaccination with either mRNA or vector based vaccines.

Results A minimum of 10 B cells/µL in the peripheral circulation was necessary in RTX patients to mount seroconversion to anti-S1 IgG upon SARS-CoV-2 vaccination. RTX patients lacking IgG seroconversion showed reduced antigen-specific B cells, lower frequency of TfH-like cells as well as less activated CD4 and CD8 T cells compared to IgG seroconverted RTX patients. Functionally relevant B cell depletion resulted in impaired IFNγ secretion by spike-specific CD4 T cells. In contrast, antigen-specific CD8 T cells were reduced in patients independently of IgG formation.

Conclusions Patients receiving rituximab with B cell numbers above 10 B cells/µl were able to mount humoral and more robust cellular responses after SARS-CoV-2 vaccination that may permit optimization of vaccination in these patients. Mechanistically, the data emphasize the crucial role of co-stimulatory B cell functions for the proper induction of CD4 responses propagating vaccine-specific B and plasma cell differentiation.

B cells seem to give a biomarker of antibody responses

It seems to me that the manufacturers/government should investigate this pretty soon…..because it they don’t someone else will. The data is mounting. Measure CD19 B cell levels check there are 2% CD19 B cells (>10cells/microlitre), boost with vaccine and measure antibody response 1-2 weeks later. You may need to delay the ocrelizumab dose to achieve this level in more people. Is it worth the effort. However remember many people with not get this B cell level. Do this before mass boosters occurs

COI Multiple but not relevant.

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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MouseDoctor

12 comments

  • Hi MD! I’m struggling to interpret what it means to have a T cell response even if there is little or no B cell / antibody response. Does that mean that these patients are just as likely to catch Covid as someone who is unvaxxed (because they have no antibodies), but if they catch Covid the likelihood of it being severe is more similar to the vaxxed population (because their T cells are already primed to fight it)?

    • It is difficult to be sure but it.points to the fact that you have immunity that can get rid of the virus so you are.less likely to have problems compared to unvaccinated people whether you. Catch covid may depend on the level of antibodies we have to see if people with ms are any different than general.population

      • Got it, makes sense. I basically have no antibodies after vaccination, so sounds like I’m just as likely to catch Covid as an unvaxxed person. But hopefully able to fight it off more like a vaxxed person.

        In case you are collecting data points, I had a whopping 0.07 units of antibodies in the test for vaccination immunity (igg spike protein) 6 weeks after my second Pfizer shot after 5 years on Ocrevus. Anything under 0.7 was considered “negative”, and a friend who got the same test the exact same number of weeks as me after her second Pfizer shot had 38+ units.

        • We are collecting but the problem is what does 0.07 mean? They are all assay specific. send you bloods to use and we may give you a 3,000 it means just as much as a 0.7 essentially nul points but if you get 250,000 you’re happy

  • Hey MD
    Any idea when data on covid outcomes in vaccinated anti-cd20 patients might appear? Think we’ll know by the end of 2021?
    Thanks a lot for keeping us up to date.

    • Hopefully never as all vaccinated people wont get COVID:-) However in UK we are on a crest of wave an infective wave and when it happens we will know about it. I guess however the information will be limited if only 3000 people were captures in global initiative then it will be yes in vaccinated people

  • Good evening. In case it helps, I report here my story and case.
    I am 37yo, male, MS diagnosed in 2005, on Ocrevus since July 2018 (after almost 10years on Natalizumab, and before Avonex for about 2years).
    I very likely had Covid on March 2020 (very first wave), although at that time I did not do any PCR (it was impossible those weeks): fever at 37,5degree for two days, cough, loss of smell and taste, the group of people I had been with the weekend before those symptom developed the same symptoms (some even worse and lasting longer). While all of these friends tested positive for antibodies, I instead tested negative (did my first serological 8 weeks after the onset of those symptoms).
    I took my vaccine shots (Pfizer) on April 28 and May 18, respectively 11 and 13 weeks after the last Ocrevus infusion (that occurred on Feb. 12, 2021). Today I got the results of my serological test (ECLIA method, performed on July 24) and the result is: <0,4 (U/ml), the reference to determine positivity being 0,8. Bad news, right? I used to be a very social and proactive person, and the fear of getting infected and infecting others is preventing me from regaining my social life, as I don't feel safe.
    Just in case this info is useful: I had done a serological test in a different lab about two weeks before the first vaccine shot (April 9), and the IGG result was 1,55 (AU/ml), with reference to determine positivity being 10,0 (CLIA method). Any comments would be welcome.
    Thanks for all your work and God bless the T-cells!

    • Obviously you have not made an antibody responses I think with a 3 month delay, there are few people who made a response.

      As for the antibody assay it is hard to know what the values mean and with regard to positivitiy we dont know protective levels

      • Thank you for your answer. Yes, no antibody responses. Fingers crossed for the T-cells protection, then… Probably due to that protection I was able to overcome covid last year (apparently I had a mild form, as described above). Hopefully the vaccine at least strengthened that protection… Thanks again for your answer.

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