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  • COVID-19 vaccine response in people with multiple sclerosis

    NOTE: THIS IS A PREPRINT AND HAS NOT BEEN PEER REVIEWED. BUT THERE ARE MANY RESPECTED AUTHORS. -D

    COVID-19 vaccine response in people with multiple sclerosis


    Emma C Tallantyre, Nicola Vickaryous, Valerie Anderson, Aliye Nazli Asardag, David Baker, Jonathan Bestwick, Kat h Bramhall, Randy Chance, Nikos Evangelou, Katila George, Gavin Giovannoni, Leanne Grant, Katharine E Harding, Aimee Hibbert, Gillian Ingram, Meleri J ones, Angray S Kang, Samantha Loveless, Stuart J Moat, Neil P Robertson, Klaus Schmierer, Sita Navin Shah, Jessica Simmons, Matthew Upcott, Mark Willis, Stephen Jolles, Ruth Dobson

    doi: https://doi.org/10.1101/2021.07.31.21261326

    This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.Abstract

    Objective To investigate the effect of disease modifying therapies on serological response to SARS-CoV2 vaccines in people with multiple sclerosis

    Methods 473 people with multiple sclerosis from 5 centres provided one or more dried blood spot samples and questionnaires about COVID-19. Information about disease and drug history was extracted from their medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV2 receptor binding domain. Seropositivity was expressed according to validated cut-off indices. Antibody titers were partitioned into tertiles using data from people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (Univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following SARS-CoV2 vaccine according to disease modifying therapy. We used regression modelling to explore the effect of factors including vaccine timing, treatment duration, age, vaccine type and lymphocyte count on vaccine response.

    Results Compared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio 0.03; 95% confidence interval 0.01-0.06, p<0.001) and fingolimod (odds ratio 0.41; 95% confidence interval 0.01-0.12) were associated with lower seroconversion following SARS-CoV2 vaccine. All other drug groups did not differ significantly from the untreated cohort. Time since last anti-CD20 treatment and total time on treatment were significantly related with response to vaccination. Vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications.

    Interpretation Some disease modifying therapies carry a risk of attenuated response to SARS-CoV2 vaccination in people with MS. We provide recommendations for the practical management of this patient group.
    Dave Bexfield
    ActiveMSers

  • #2
    This is going to be an evolving topic that we need to watch closely. Right now, the anti-CD20 therapies (Ocrevus, Rituxan, Kesimpta) appear to be the biggest problem child. The research is still fuzzy on S1P modulators. They appear to respond well to boosters. Here are some posts by neuros that you'll want to read if you are on any of these medications if you want to make better sense of everything.

    More on fingolimod (Gilenya). It is unclear how other similar drugs (Mayzent, Zeposia, Ponvory) work with the vaccines.

    https://multiple-sclerosis-research....lures-perhaps/

    https://multiple-sclerosis-research....ion-responses/
    Dave Bexfield
    ActiveMSers

    Comment


    • #3
      5 things a neuroimmunologist wants you to know about COVID-19 vaccines and MS DMTs

      https://www.mssociety.org.uk/researc...es-and-ms-dmts
      Dave Bexfield
      ActiveMSers

      Comment


      • #4
        Here is a summary of neuro Gavin Giovannoni's thoughts on the subject.

        https://gavingiovannoni.substack.com...nd-ms/comments
        Dave Bexfield
        ActiveMSers

        Comment


        • #5
          And the story of S1P modulators (Gilenya, et al) is still unfolding. Maybe it's the type of vaccine that inhibits response?

          https://multiple-sclerosis-research....-virus-vaccine
          Dave Bexfield
          ActiveMSers

          Comment


          • #6
            Ann Rheum Dis
            . 2021 Aug 6;annrheumdis-2021-220626.
            doi: 10.1136/annrheumdis-2021-220626. Online ahead of print.Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression

            Maria Prendecki # 1 2, Candice Clarke # 3 2, Helena Edwards 3 2, Stacey McIntyre 3, Paige Mortimer 3, Sarah Gleeson 3 2, Paul Martin 3 2, Tina Thomson 2, Paul Randell 4, Anand Shah 5 6, Aran Singanayagam 7 8, Liz Lightstone 3 2, Alison Cox 4, Peter Kelleher 4 7, Michelle Willicombe 3 2, Stephen P McAdoo 3 2
            Affiliations expandFree PMC article

            Abstract

            Objective: There is an urgent need to assess the impact of immunosuppressive therapies on the immunogenicity and efficacy of SARS-CoV-2 vaccination.

            Methods: Serological and T-cell ELISpot assays were used to assess the response to first-dose and second-dose SARS-CoV-2 vaccine (with either BNT162b2 mRNA or ChAdOx1 nCoV-19 vaccines) in 140 participants receiving immunosuppression for autoimmune rheumatic and glomerular diseases.

            Results: Following first-dose vaccine, 28.6% (34/119) of infection-naïve participants seroconverted and 26.0% (13/50) had detectable T-cell responses to SARS-CoV-2. Immune responses were augmented by second-dose vaccine, increasing seroconversion and T-cell response rates to 59.3% (54/91) and 82.6% (38/46), respectively. B-cell depletion at the time of vaccination was associated with failure to seroconvert, and tacrolimus therapy was associated with diminished T-cell responses. Reassuringly, only 8.7% of infection-naïve patients had neither antibody nor T-cell responses detected following second-dose vaccine. In patients with evidence of prior SARS-CoV-2 infection (19/140), all mounted high-titre antibody responses after first-dose vaccine, regardless of immunosuppressive therapy.

            Conclusion: SARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppression, when assessed by a combination of serology and cell-based assays, although the response is impaired compared with healthy individuals. B-cell depletion following rituximab impairs serological responses, but T-cell responses are preserved in this group. We suggest that repeat vaccine doses for serological non-responders should be investigated as means to induce more robust immunological response.
            Dave Bexfield
            ActiveMSers

            Comment


            • #7
              Timing matters when you last got your Ocrevus or Rituxan. A LOT. -D

              Development of humoral and cellular immunological memory against SARS-CoV-2 despite B-cell depleting treatment in multiple sclerosis.

              Klara Asplund Högelin1,5 , Nicolas Ruffin1,5, Elisa Pin2 , Anna Månberg2 , Sophia Hober3 , Guro Gafvelin4 , Hans Grönlund4 , Peter Nilsson2 , Mohsen Khademi1 , Tomas Olsson1 , Fredrik Piehl1 , Faiez Al Nimer1,6,* 1 Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:04, 171 76, Stockholm, Sweden 2 Division of Affinity Proteomics, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 17165, Stockholm, Sweden. 3 Division of Protein Technology, Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, 17165, Stockholm, Sweden. 4 Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine L8:02, 171 76, Stockholm, Sweden

              Summary

              B-cell depleting therapies (BCDTs) are widely used as immunomodulating agents for autoimmune diseases such as multiple sclerosis. Their possible impact on development of immunity to SARS-CoV-2 has raised concerns with the COVID-19 pandemic. We here evaluated the frequency of COVID-19-like symptoms and determined immunological responses in participants of an observational trial comprising several multiple sclerosis disease modulatory drugs, (COMBAT-MS; NCT03193866) and in eleven patients after vaccination, with a focus on BCDT. Almost all seropositive and 17.9% of seronegative patients on BCDT, enriched for a history of COVID-19-like symptoms, developed anti-SARS-CoV-2 T-cell memory and T-cells displayed functional similarity to controls producing IFN-γ and TNF. Following vaccination, vaccine-specific humoral memory was impaired, while all patients developed a specific T-cell response. These results indicate that BCDTs do not abrogate SARSCoV-2 cellular memory and provide a possible explanation as to why the majority of patients on BCDTs recover from COVID-19

              FULL PAPER: https://www.cell.com/iscience/pdf/S2...showall%3Dtrue
              Interestingly, for the patients who had received an infusion within four months before their first dose, only two out of five (40%) had detectable SARS-CoV-2 specific antibodies four weeks after vaccination. The remaining patients with more than 4 months since last infusion, all five out of five (100%) had detectable antibodies four weeks after vaccination. However, regardless of time since last infusion or serology status, all pwMS developed a robust and specific T-cell response (Figure 6C).

              FROM BARTS:

              This first surfaced many moons ago on SSRN as a preprint when only people taking anti-CD20 who were naturally infected were included. It suggested that most people made an anybody response when infected with SARS-CoV-2 (Only about 25% seroconverted on anti-CD20 (which has been shonw by many others) and not on anti-CD20) and that vaccines were not going to be a problem….How wrong that turned out to be, but the paper now surfaces with vaccine data. Guess what.?…Yep the antibody responses after vaccination is blunted and there is a T cell response so it supports a number of studies by the tortoises…so this is yet another paper saying the same thing. So we can be increasingly confident that this story is correct. What it means is the question I can’t answer.

              They show you can make antibodies when there are no B cells in the blood

              They also say “When analyzing the percentages of B-cells, all seronegative samples displayed less than 0.2% B-cells of live lymphocytes. Interestingly, among the seropositive pwMS, there were also two samples with less than 0.2% B-cells (Figure 6D), indicating that a virtual absence of B-cells in peripheral blood is not a good predictor of not producing detectable antibodies after vaccination”. However you can see that if you have 1% B cells you are more likely to seroconvert. Those over 6 months delay are more likely to seroconvert 5/5 verse 2/5 less than 6 months

              https://multiple-sclerosis-research....-hare-arrives/
              Dave Bexfield
              ActiveMSers

              Comment


              • #8
                Here's the latest opinion from Bart's out of the UK on the issue of anti-CD20 therapy. Still a bit of limbo, I'm afraid, but the answers appear to be getting clearer. -D

                I have moved my position from getting vaccinated ASAP to let’s time your vaccine to give you the best chance of seroconverting. This means waiting for B-cell reconstitution post-anti-CD20 before vaccinating.

                An adaptive vaccination/vaccine-booster strategy is logistically challenging for the simple reason that B-cell reconstitution post anti-CD20 therapy is quite variable. This means that after a certain period of time, say 9 months after your last dose of ocrelizumab, 6 months after your last dose of rituximab and 4 months after your last dose of ofatumumab you will have to have monthly B-cell counts to make sure your peripheral B-cell count is above 10 B-cells/mm3 before you can get vaccinated. I also suspect we will then have to check if you seroconvert and if not re-vaccinate you before redosing with the relevant anti-CD20.

                https://multiple-sclerosis-research....dosing-or-not/
                Dave Bexfield
                ActiveMSers

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