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
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 COVID–19 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.