The data is surfacing and it tells us that people taking ocrelizumab: (a) Make an anti-viral T cell response and (b) make a blunted antibody response.
Apostolidis et al 2021,https://www.medrxiv.org/content/10.1101/2021.06.23.21259389v1.full
Coppola N et al. Preliminary evidence of blunted humoral response to SARS-CoV-2 mRNA vaccine in multiple sclerosis patients treated with ocrelizumab. Neurol Sci. 2021 Jun 15:1–4. doi: 10.1007/s10072-021-05397-7.
Is there a guarentee that you will make an antibody response when you get the jab……….Answer = No
If you want a postive response COVID19 antibody test get yourself an anti-Spike test, An anti-receptor binding domain of spike test is less likely to be as positive. If you want an irrelevant test… get a nucleocapsid test…Yep quite a few people have done this and is no use for many vaccines as they are all based on Spike.
Why do this?
Look at the data below if you do anti-Spike the majority of people are positive using 1ug/ml cut off and the 10microcgramme/ml cutoffs (line). Receptor binding domain is only a small fraction of Spike so it makes sense you have more to whole Spike. However the antibodies to receptor binding domain stop the virus attaching to your cells to prevent infection. The higher the level, the better chance you have to block the virus from infecting and this is important with the Greek letter named variants of concern, as they need more antibody to stop them infecting.
Do people make an antibody response it they seemingly have no B cells in the Blood?: YES sometimes. Therefore lack of B cells in your blood before vaccination does not say you won’t make a vaccine response, but on the flip side if you have B cells in your blood you are probably more likely will make a vaccine response. You could measure this and if you have B cells…green light…vaccinate you will probably make an antibody response.
Do you make an antibody response if you have more than 2% B cells: Possibly Yes?
Do you make an antibody response if you have more than 0.1% B cells: Possibly Yes? However this level is at the bottom of the pile, therefore, if you have a blood test before you are vaccinated and you have say above 0.2% B cells (need more data) or 1% B cells then you are likely going to make a B cell response to the COVID vaccine. https://www.medrxiv.org/content/10.1101/2021.06.23.21259389v1.full
However already I have to say be warned!!. There will be exceptions and we saw this (doi: 10.1007/s00415-021-10663-x.) last week. Lymphocyte level 1.22 x 10*9/L and 1% CD19 B cells and no antibody response detected with an interval of 5 months.
How do you guarentee you will have B cells…you can’t because people repopulate their B cells at very different rates. Some get back to lower limit of normal quickly (around 6 months) some take (three or more) years. So in this example essentailly no one had 1% B cells less than 6 months after infusion….This is why they do it every 6 months. Therefore to increase the chance of B cells above 0.2% you would probably have to delay your next dose of ocrelizumab. However what is the risk that disease reactivates?
What is 1% of lymphocyte level? This is where it is not good science because it should be based on absolute numbers not percentages. In healthly individuals the lymphocyte range is about 1000-4000cells/microlitre at 1% this is 10 to 40 cells/microlitre. So point 0.1% is 1 cell/ul so perhaps if you are 2 cells/ul that could be enough.
However, be warned again
Based on the phase II extension data at 6 months after dosing there are still people with 0 CD19 cells/uL counts and at 9 months there are still people at 0, but at 12 months there people at 2 cells and therefore the question is what are the risks of disease reactivation if you do this. Exactly how many I will have a look at the data. It may not be worth the effort
During the pandemic ProfG has suggested some immunity is better than no immunity, but as fears ease and boosters arrive or you live in a area with little virus, Do you try and optimise your chances of an antibody response or plough on regardless? The answer is based on Opinion Only..We don’t have the data
Are you convinced the level of antibody is enough? I will say that of the antibody reponses in CD20-treated individuals that are positive, they are generally lower than occurs in people who have not had anti-CD20.
There has already been data on the influence of rituximab and the influence of relapse.
Maarouf A, Rico A, Boutiere C, Perriguey M, Demortiere S, Pelletier J, Audoin B; Under the aegis of OFSEP. Extending rituximab dosing intervals in patients with MS during the COVID-19 pandemic and beyond? Neurol Neuroimmunol Neuroinflamm. 2020 Jun 25;7(5):e825.
We can look at rituximab data where dosing was stopped because of the COVID-19 pandemic. 33 people were stopped and not one relapse developed despite stopping for 8-31 months and there are at least 7 people without B cells at 9 months but with only 5 with B cells definately above B cells at 1%.
Barun B, Gabelić T, Adamec I, Babić A, Lalić H, Batinić D, Krbot Skorić M, Habek M. Influence of delaying ocrelizumab dosing in multiple sclerosis due to COVID-19 pandemics on clinical and laboratory effectiveness. Mult Scler Relat Disord. 2021 Feb;48:102704.
The mean time between two ocrelizumab infusion during the lockdown was 7.72±0.64 (range 6.07 to 8.92) months. The mean time between last ocrelizumab infusion and the lymphocyte sampling prior to post COVID infusion was 6.59±0.95 (range 5.18 to 8.49) months. In this period, none of the studied patients had a relapse.
Tazza F, Lapucci C, Cellerino M, Boffa G, Novi G, Poire I, Mancuso E, Bruschi N, Sbragia E, Laroni A, Capello E, Inglese M. Personalizing ocrelizumab treatment in Multiple Sclerosis: What can we learn from Sars-Cov2 pandemic? J Neurol Sci. 2021 May 20;427:117501. doi: 10.1016/j.jns.2021.117501. During SARS-CoV-2 pandemic, we adopted a personalized delayed protocol for ocrelizumab infusions in Relapsing Remitting Multiple Sclerosis (RRMS) patients according to the national recommendations. Out of the 83 RRMS patients whose infusion was scheduled between March and December 2020, 56 patients experienced a delay in treatment based on MS severity and SARS-CoV2 infection risk profile. In most cases, the immunophenotype was performed monthly to guide re-infusions. Specifically, B CD19 + cells repopulation rate was monitored. Mean infusion delay was 103.1 [SD 40.6] days, and none of the patients presented relapses or active disease at MRI at the end of the observation period. Treatment naïve status and the interval between immunophenotyping and the last ocrelizumab infusion were predictors of earlier B CD19 + cells repopulation……Our findings suggest that a personalized treatment with a delayed infusion schedule does not compromise ocrelizumab short-term efficacy and may help to lengthen the therapeutic window for an effective response to SARS-CoV2 vaccine.
There are UK studies in the pipeline when people stopped dosing ocrelizumab last March, which address this. There will be more anti-CD20 data following vaccination. As these surface it will start to answer the risks of a delay and help determine whether it is deemed necessary. It may not be and maybe unwise
However, you will not know this until vaccinated individuals get infected. Lets hope it doesnt happen
The rate of re-infection is about 1:1000% so it will happen but this information will be a trickle. I am sure most, if not all people will do OK as the T cell response and your, weight (BMI), sex and age, if you have this demographic, will protect you.
SARS-CoV-2 vaccine breakthrough infections are asymptomatic or mildly symptomatic and are infrequently transmitted.Rovida, F., Cassaniti, I., Paolucci, S., Percivalle, E., Sarasini, A., Piralla, A., Giardina, F., Sammartino, J. C., Ferrari, A., Bergami, F., Muzzi, A., Novelli, V., Meloni, A., Grugnetti, A. M., Grugnetti, G., Rona, C., Daglio, M., Marena, C., Triarico, A., Lilleri, D., Baldanti, F.10.1101/2021.06.29.21259500 — Posted: 2021-07-03
Vaccine breakthrough SARS-CoV-2 infection was monitored in 3694 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV2 infection was detected in 33 subjects, with a 3-months cumulative incidence of 0.90% and 0.42% in SARS-CoV-2-naïve and experienced subjects, respectively. Vaccine protection was 87% in naïve and 94% in experienced subjects when compared with a pre-vaccination control group. The infection was mildly symptomatic in 16 (48%) and asymptomatic in 17 (52%) subjects. Virus isolation was positive in 7/13 (54%) symptomatic and 4/8 (50%) asymptomatic subjects tested, and B.1.1.7 lineage was detected in all subjects. Antibody and T-cell responses were not reduced in subjects with breakthrough infection. Evidence of virus transmission, determined by contact tracing, was observed in two (6.1%) cases.This real-world data confirm the protective effect of BNT162b2 vaccine. A triple antigenic exposure, as occurring in experienced subjects, may confer a higher protection. Virus transmission from vaccinated subjects is infrequent. As a possible recipient of a death sentence if I caught covid, I have been cautious. But I would also want to know the safety of any decision made.
Should a pilot be done? Maybe there will soon be enough data to make a call. I expect the argument will be “T cells are enough” and they will test antibodies against Spike. However, this is not just about ocrelizumab and MS, but rituximab and other conditions and ofatumumab too. I sure there there will always people who do not give a good vaccine response. Can you optimise this?
Interferon-gamma release assay testing to assess COVID-19 vaccination response in a SARS-CoV-2 seronegative patient on rituximab: a case report. Int J Infect Dis. 2021 Jun 30:S1201-9712(21)00542-7. doi: 10.1016/j.ijid.2021.06.054
I am not making any recomendations …..More data will surface
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