I was wondering if I had presented this one, but there is nothing you havent heard a few times,,,,so I think we can safely say that many people taking ocrelizumb don’t make an antibody response after SARS-CoV-2 but do make a T cell response. We can’t put this idea to bed yet as it will be repeated again a few more times I suspect and we have vaccine three and four to talk about. We have a new contribution on that one so more of that soon.

This current paper indicates that you need B cells to be present to increase the chance of making antibody. It also suggests that “clinical efficacy seems to outlast B cell depletion” and “Patients with delayed B cell-repopulation kinetics might be ‘overtreated’ by receiving OCR every 6 months”. 

Räuber S, Korsen M, Huntemann N, Rolfes L, Müntefering T, Dobelmann V, Hermann AM, Kölsche T, von Wnuck Lipinski K, Schroeter CB, Nelke C, Regner-Nelke L, Ingwersen J, Pawlitzki M, Teegen B, Barnett MH, Hartung HP, Aktas O, Albrecht P, Levkau B, Melzer N, Ruck T, Meuth SG, Kremer D. Immune response to SARS-CoV-2 vaccination in relation to peripheral immune cell profiles among patients with multiple sclerosis receiving ocrelizumab. J Neurol Neurosurg Psychiatry. 2022 Feb 22:jnnp-2021-328197. doi: 10.1136/jnnp-2021-328197.

Background: Vaccination has proven to be effective in preventing SARS-CoV-2 transmission and severe disease courses. However, immunocompromised patients have not been included in clinical trials and real-world clinical data point to an attenuated immune response to SARS-CoV-2 vaccines among patients with multiple sclerosis (MS) receiving immunomodulatory therapies.

Methods: We performed a retrospective study including 59 ocrelizumab (OCR)-treated patients with MS who received SARS-CoV-2 vaccination. Anti-SARS-CoV-2-antibody titres, routine blood parameters and peripheral immune cell profiles were measured prior to the first (baseline) and at a median of 4 weeks after the second vaccine dose (follow-up). Moreover, the SARS-CoV-2-specific T cell response and peripheral B cell subsets were analysed at follow-up. Finally, vaccination-related adverse events were assessed.

Results: After vaccination, we found anti-SARS-CoV-2(S) antibodies in 27.1% and a SARS-CoV-2-specific T cell response in 92.7% of MS cases. T cell-mediated interferon (IFN)-γ release was more pronounced in patients without anti-SARS-CoV-2(S) antibodies. Antibody titres positively correlated with peripheral B cell counts, time since last infusion and total IgM levels. They negatively correlated with the number of previous infusion cycles. Peripheral plasma cells were increased in antibody-positive patients. A positive correlation between T cell response and peripheral lymphocyte counts was observed. Moreover, IFN-γ release was negatively correlated with the time since the last infusion.

Conclusion: In OCR-treated patients with MS, the humoral immune response to SARS-CoV-2 vaccination is attenuated while the T cell response is preserved. However, it is still unclear whether T or B cell-mediated immunity is required for effective clinical protection. Nonetheless, given the long-lasting clinical effects of OCR, monitoring of peripheral B cell counts could facilitate individualised treatment regimens and might be used to identify the optimal time to vaccinate.

You can have a read of these if you are interested

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;16:41-50.

The ocrelizumab phase II extension trial suggests the potential to improve the risk: Benefit balance in multiple sclerosis.Baker D, Pryce G, James LK, Marta M, Schmierer K.Mult Scler Relat Disord. 2020; 44:102279.

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 Nov;202(2):149-161

However the implication that we dont know what will happen with infections is not really correct..we do know

Breakthrough SARS-CoV-2 infections in immune mediated disease patients undergoing B cell depleting therapy Calabrese, C. M., Husni, E. M., Moss, B. M., Fernandez, A. J., Jin, Y., Kirchner, E., Calabrese, L. H.10.1101/2022.02.21.22271289 — Posted: 2022-02-22

Abstract Objectives: Immunocompromised patients with immune mediated inflammatory diseases (IMIDs), undergoing therapy with B cell depleting agents are among the most vulnerable to experience severe COVID-19 disease as well as respond sub-optimally to SARS CoV-2 vaccines yet little is known about the frequency or severity of breakthrough infection in this population. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Methods: Utilizing specific ICD codes the pharmacy records and COVID-19 registry at the Cleveland clinic were used to identify all patients with IMIDS treated with B cell depleting monoclonal antibodies who were vaccinated against SARs CoV-2 and experienced breakthrough infections. Each EMR record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, other therapies, details of B cell depleting therapy, and outcomes. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results: Of 1696 IMIDS patients on B cell depleting therapies 74 developed breakthrough COVID-19. Outcomes were severe with 24 (35%) hospitalized, 11 (15%) patients requiring critical care and 6 (8 %) deaths. Monoclonal antibodies were used on an outpatient basis to treat 21 with only a single patient requiring hospitalization without oxygen support and no deaths. Conclusions: In IMIDS patients on B cell depleting therapies breakthrough infections are frequent and associated with severe outcomes. Outpatient use of monoclonal antibody therapy was associated with enhanced clinical outcomes.

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  • I am on Ocrevus, had all 3 Pfizer shots, got COVID in January, have next infusion in March, will I be more immuncompromised again and lose natural immunity?

  • I found out recently some hospitals here in Germany are giving their Ocrevus patients with poor immune responses moniclonal antibody infusions every 2 months to give them protection. Whereas in other areas it’s only if you are immune suppressed and test positive for Covid. Other countries then, such as Ireland, where we’re from and where all safeguards and mask wearing have been dropped, don’t automatically give it to immune suppressed patients who test positive for Covid. I was told they would only give it if I was ill enough to be hospitalised. Surely with no antibodies and a poor T cell response that’s a given. Surely prevention is better than cure and is there not an argument for making Covid moniclonal antibody use as a preventative treatment the norm in patients so dangerously immune compromised? I understand it’s now less effective with new strains but prior to that it showed great efficacy.

      • Yes, not much point given the BA.2 variant now but Omicron has only really hit most of Europe since December. Prior to this it could have been used to protect vulnerable people and allow us to come out of hiding and have some mental respite from the isolation. I’m just curious as to whether there was a reason it was never used in this preventative way. Limited supplies?

        • yep I agree….the trials were not designed to show prevent, but the astrazeneca antibody was designed to be and was shown to be prophylactic

  • This current paper indicates that you need B cells to be present to increase the chance of making antibody

    Historricaly you never like this idea

    nice work

  • I must say I’m very sad to see what the final paper had to say. 35,1% hospitalization! That’s a lot. Hopefully the Omicron variant will turn out to be milder also in anti-cd20 treated pwms.
    It also saddens me greatly that Scandinavians have a very low supply of mAbs and no antivirals – except Remdesivir in severe cases. In Norway you might get sotrovimab if you’re hospitalized or have an abundance of extra risk-factors. It’ll be exciting to see the results for Sweden / Norway after the Omicron wave has passed.

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