46 Comments
Aug 23, 2021Liked by Gavin Giovannoni

I very much like the user friendly advice in the newsletter but in this instance that is somewhat tricky with school age children in the U.K. at this point in time! Particularly as my 11 year old is due to start secondary school and will be mixing with many more kids than before, and cannot access a vaccine on the current rules in the U.K.

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I assume you are prehabilitating? If not please read this Newsletter.

https://gavingiovannoni.substack.com/p/prehabilitation-the-ultimate-in-self

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I know it is difficult. Saying this if you have school-aged children you are relatively young so if you get COVID-19 you are likely to be okay. Also, T-cell immunity from the vaccine doses 1 and 2 may be sufficient to reduce your chances of getting the severe disease. I am assuming you are on either an anti-CD20 or an S1P-modulator.

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Thanks. Yes - I am on ocrelizumab. I do appreciate that it’s not all about antibodies.

My 8 year old took great delight in telling me I was old this morning so it’s good to hear I still count as relatively young for something!

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Aug 24, 2021Liked by Gavin Giovannoni

Love the newsletter.

Question - have you heard of anyone or is there anyone here on an anti-CD20, who has been fully vaccinated but confirmed to not have had an antibody response (negative spike and nucleocapsid) who has then been infected (via a positive nucleocapsid test) asymptomatically? I know that’s a lot of conditions but I’m really curious to see if people like this exist, or does everyone without B cells and no antibodies (despite vaccination) get infected symptomatically, yet the majority of those avoid severe disease.

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No, I am not aware.

Please note if you have had the vaccine you should be anti-spike antibody positive and anti-nucleocapsid antibody-negative unless you have the Chinese whole SARS-CoV-2 inactivated viral vaccine. All the currently licensed vaccines in the UK, Europe and USA are based on the spike protein only.

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Aug 23, 2021Liked by Gavin Giovannoni

So first time around I was able to get vaccinated about a month after I was due for my next infusion and then I got 2 pfizer doses waited another 3 weeks then got vaccinated. I tested my antibodies before and then 5 months after. I had no B cell antibodies before against covid at 5 months after vaccination I had about 50% of the antibody level required for it to be considered positive for the antibodies on the test. I had a robust T cell response though considered positive for covid response. My question is this now at about 6 months since I was vaccinated and about 5 months since my last infusion I am thinking of getting the booster. I could wait a couple months to potentially have more B cell repopulated but then that is waiting without the booster. I plan to wait about a month after the booster to get ocrevus again. What are your thoughts about getting booster now 5 months after my last infusion? Also do you think waiting one month post booster is sufficient before getting next infusion Thanks

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Seems reasonable. You are one of the lucky 1 in 5 that thas made an antibody response to the vaccine. You have T-cell responses as well so you should be protected from getting severe COVID-19. I am interested to know who tested you? T-cell responses and even anti-spike antibody responses are being done routinely.

To the best of my knowledge, T-cell response assays for COVID-19 have not been validated for clinical use; at least not in the UK.

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Aug 23, 2021Liked by Gavin Giovannoni

If you have MS and not on any dmt does having all of these Vaccines excite the immune system too much and therefore potentially cause a relapse?

Also when will people know if antibodies have depleted enough to have to need another booster and should we not be waiting for a tweaked vaccine?

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No, we have good data now that vaccinations, including COVID-19 vaccines, don't trigger relapses. However, it looks like COVID-19 itself trigger relapses.

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Sorry, but this is not true. I have been relapse-free since 2012, and, trusting the doctors, I went ahead and got the 1st pfizer vaccine at the very end of July. Within two weeks, I have 5 new enhancing lesions on my brainstem, a numb hand, extremely diminished sense of taste, numb face, lips & nose, and slurred speech. I was diagnosed with MS 16 years ago (the flu vaccine gave me bilateral optic neuritis!). I stopped taking dmts in 2016 because of horrible side effects. I've been getting regular MRIs and have had zero new lesions from 2012 until I got the vaccine. My neurologist (who I wish I had consulted, but so hard to get an appointment), said that they are in fact seeing people who are not taking dmts have relapses after vaccination. This has pretty much ruined my life. I felt healthy, and even questioned whether I had perhaps been misdiagnosed, until now. Please trust your instincts, and if you aren't on dmts, be very wary of getting vaccinated. My biggest joy in life was cooking and eating and sharing food with my family. Now I have no joy.

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All I am doing is quoting the published literature. As millions of people with MS get vaccinated there will be people who have relapses and reactivation of their MS disease activity post-vaccination. The question is this greater than the back ground rate? The following is the Israeli data.

Achiron et al. COVID-19 vaccination in patients with multiple sclerosis: What we have learnt by February 2021. Mult Scler. 2021 May;27(6):864-870. doi: 10.1177/13524585211003476. Epub 2021 Apr 15.

Background: Since vaccination against coronavirus disease 2019 (COVID-19) became available, risks related to vaccinating patients with multiple sclerosis (MS) need to be carefully assessed.

Objective: Characterize safety and occurrence of immediate relapses following COVID-19 vaccination in a large cohort of MS patients.

Methods: We assessed the safety of BNT162b2 COVID-19 vaccination in adult MS patients.

Results: Between 20 December 2020 and 25 January 2021, 555 MS patients received the first dose of BNT162b2 vaccine and 435 received the second dose. There were three cases of COVID-19 infection encountered after the first dose. Safety profile of COVID-19 vaccine was characterized by pain at the injection site, fatigue, and headache. No increased risk of relapse activity was noted over a median follow-up of 20 and 38 days after first and second vaccine doses, respectively. The rate of patients with acute relapse was 2.1% and 1.6% following the first and second doses, respectively, similar to the rate in non-vaccinating patients during the corresponding period. Mild increase in the rate of adverse events was noted in younger patients (18-55 years), among patients with lower disability (Expanded Disability Status Scale (EDSS) ⩽3.0), and in patients treated with immunomodulatory drugs.

Conclusion: COVID-19 BNT162b2 vaccine proved safe for MS patients. No increased risk of relapse activity was noted.

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Seems like “vigilance” for some is a constant “tweeking” of infusion timing, of work and child schedules, blood tests, and other once normal routines, all done with no particular end in site and no guaranteed result. Really, it’s a new life-style with vigilence being a daily routine for a long time. So a concern that comes up is “burn-out”. A far cry from what Roche was strongly implying in their TV ad during an ABC news special on Covid; that being that Ocrevus will bring your life back to normal. Shame on them. I’d like to rattle off a bunch or curse words and I’m sure others, especially those responding to the TV ad, would too.

I commend (not that he needs it), Dr. G’s admission that there are other DMTs. But here’s my evolution on that subject (trying to push the discussion forward to its next logical step)…. If I were at an earlier stage in my “MS career”, I definitely would be researching and considering the commitment and sacrifice of the total washing out of my immune system (reconstitution(?) and doing whatever was necessary to isolate and protect myself for the period afterwards, especially if I were on a B-cell depleting DMT now. It would surely be a huge project, but the payoff afterwards, would be an MS remission (hopefully complete), PLUS a normal immune system able to tackle whatever Covid threw my way. I’d no longer be pulling my hair out trying to keep myself or others safe, or, ignoring all that while having in the back of my mind a dread of what could happen, being so careless.

And just on a side note for any MS newbies stumbling across this newsletter- there are many avenues of MS information stemming from and around Dr. G., including many other experts like the Mouse Doctor (all associated with “Multiple Sclerosis Research Blog” [google it]), who post almost daily about ongoing real time MS issues for newbies and seniors alike. The information is priceless and probably not what you are going to see in filtered sources, which is just about everywhere else. I’ve been following MS stuff for 30 years, and there is nothing like this. Want information? Almost everything is there,…good information. And you might even get a decent accurate response to a question you have, from an expert in the trenches. It’s all priceless.

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Re: "A far cry from what Roche was strongly implying in their TV ad during an ABC news special on Covid; that being that Ocrevus will bring your life back to normal."

Did it really say this? This is why direct to consumer drug advertising is not allowed in the EU and the UK. Not sure how any MS DMT can claim to bring your life back to normal.

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Hello Doctor- In the winter/spring 2019 issue of The Motivator, O has an advertisement (on paper) “MS shouldn’t make you question your plans” (in large bold). The photo includes people (one black), sitting around a picnic table. Also stated is “have fewer maybes”. I mention race because the TV commercial had the same black guy, I believe. (That stuck in my mind too, maybe it shouldn’t have). The theme on TV was the same as in The Motivator, complete with playing ball and running happy children. Your plans are safe with Ocrevus, go to a party, bring the family. I don’t remember distancing or masks, either, but could be wrong.

But what really stood out to me, was that this was early 2020 (maybe April), and there were real concerns about B cell depletion back then, and there Roche is, advertising on a special ABOUT COVID, NO LESS! I think it took gull. People at Roche knew of the big questions and should have communicated with the advertising dept. to tone it down and advertise on a different program. That in itself implies to me, that “Ya, we thought about it and there’s no problem”. I remember shouting to my wife in the next room, holy “&#@”!. I don’t remember the words on TV, but it was probably similar, an advertising campaign. I was paraphrasing and to me it means about the same, if you don’t split hairs. Have an assistant look up both my references, the history is there somewhere. Careless and reckless, I thought, even back then.

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Thanks for your kind comments. The reason why I started the MS-Selfie Newsletter was to separate out content from the MS-Blog that is useful for pwMS to self-manage their MS and to curate it on a companion microsite, which will with time become a living self-help guide to manage your MS.

In comparison, the MS-Blog is mainly for interpreting research findings, which some people are not interested in. Also, my ClinicSpeak posts, with clinical management information, on the MS-Blog were never curated and are difficult to find amongst the research-related posts. I will gradually update these and transfer them onto MS-Selfie Newsletters and then onto the microsite.

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and yet HCP are saying all is well and we should be out and about with family and friends. I despair I really do.

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I think it is because of poor messaging from the governments. It is clear despite a high vaccination rate in Israel that there is a delta variant surge that is now affecting double-vaccinated elderly people who have waning immunity. The same applies to people on immunosuppressive treatments that blunt vaccine responses. This is why the FDA in the US and the UK Governments are recommending booster vaccines or 3rd doses in the vulnerable..

The message is clear we have an evolving virus that is gradually escaping vaccine immunity, we have a first-generation vaccine that is not that effective anymore, we have immunity that wanes particularly in the elderly (immunosenescence) and immunocompromised, we are seeing reinfection rates and infections in vaccinees rising. All this adds up to be careful if you are vulnerable.

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I am based in Germany and on Ocrevus. My consultant did a test to check how I responded to the Covid vaccine (not an antibody test - the test they did was a more detailed blood test that was able to check the T cell response - not sure of the more medical term for this). It came back that I did not have significant cover. This was despite me delaying my last Ocrevus infusion by 4 months in order to get the vaccine at a more optimal time that would give me the best chance of cover. I've to get a booster now at 3 months post infusion but if the vaccine didn't work at 9 months post infusion I can't see how the booster will make a difference. It seems the more the world returns to normal the more those of us in the vulnerable group have to cocoon at home.

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Yes, antibody vaccine responses post-ocrelizumab depend on having enough B-cells around. This is why for the boosters doses or 3-rd doses I am telling my patients if they want an antibody response to the vaccine they have to wait for some B-cell reconstitution.

However, if pwMS have not been vaccinated yet it is best to have the vaccine as soon as possible; some immunity is better than no immunity.

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would you describe this as „hope“ for the cd20/fing treated?

https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html

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Yes, this is one of many antibody treatments, but these will also be hampered by immune escape variants. I think the real game-changers will be the small molecular antivirals when they arrive.

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My blood results say for CD4+ T cell the result is negative for a Covid immune reaction but for CD4+ CD8+ T cell the result is positive and I have cover of 0.0145. I have no idea if that's a good level or not!? What concerns me is I delayed my last infusion until the 10-month mark thinking it would boost my chances of a good response to the vaccine but it hasn't really. So is there any point in me doing the same when getting my booster? Do I just take it as soon as I hit the 3-month post-infusion mark or is it likely to do nothing at all if the response was so poor 10-months post infusion. Thanks so much for your help on all this

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tx for reply…small molecular you mean this stuff - if it works…?

https://www.roche.com/investors/updates/inv-update-2021-06-30.htm

or something else i did not discover yet 😬 thank you!

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Thanks for the great post & newsletter. I can’t seem to find any info on people who have had both vaccination doses and then start on anti-cd20/ ocrelizumab. Would the vaccine response be blunted on starting treatment?

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I am not sure this has been studied. But once you have plasma cells that make antibody your immunity is there. Almost certainly once you have had an anti-CD20 your booster response will slightly blunted. The latter has been shown with other vaccines.

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This extremely helpful. Thank you. Curious what my wife with MS and family should fo with school.

We are in the US. My wife is on Ocrevus. She is 37. She has Pfizer and we will seek booster this fall.

My daughter is vaccinated (12 year old) we live in a > 90% vaccinated community. Cases are up but not like much of the country. She is going back to school next week. Seem reasonable or too risky?

My son is 10 so not vaccinated. We are opting for an online option for at least the first half of school. My son has adhd and autism and could use the social development skills that school offers… but he’s doing pretty well after last year all online from home honestly…. To protective of my wife to keep him at home?

I’m very worried about my wife she has terrible anxiety and I worry if we never brave returning to normal my entire family could suffer spiraling mental health challenges. Alternatively the covid risk is very real… seems like impossible choices.

I know specific advice is impossible but thought I’d ask anyways.

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This would be an ideal time for checking anti-spike antibody responses. If positive she will have the confidence to reengage with society knowing she has responded to the vaccine and has immunity.

Seroconverting post-vaccination indicates a B-cell response as well as an associated T-cell response. Not seroconverting simply looks at B-cells and does not tell you anything about T-cell responses, particularly CD8+ve responses, which may be intact.

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Thank you for the response, I didn’t realize we could test for T-cells, we will investigate that.

My wife did feel pretty sick the day after her 2nd dose. We were optimistic that was an immune response to the vaccine.

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32 years old and on Ocrevus - when you say 'to remain vigilant and to avoid crowded public spaces, to maintain social distancing if you can, to keep wearing masks and to wash your hands frequently' - I find it hard to know what this includes as everyone tries to go back to more in person activities, especially with work related things. For example what about travel abroad for work? It's one of those things that I could probably get out of, but I want to join the team etc is travelling abroad more risk than going to the pub or gym for example?! It's so hard to know!

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I agree very difficult. You have to assume you are still at risk of infection. Hopefully, once antibody tests become available you can test yourself and if you have antibodies you can be relatively confident you have some immunity.

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Are there any options that can be done privately? I keep seeing comments on the other blog of people having had them or saying they have anti bodies. There are so many options online it’s hard to know what’s the right test.🤷🏻‍♀️

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The NHS is starting to make it available nationally for UK citizens.

https://www.nhs.uk/conditions/coronavirus-covid-19/testing/antibody-testing-to-check-if-youve-had-coronavirus/

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Thank you, have registered :)

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I live in southern Australia and am a frontline worker (working in mixed population ED). I was fortunate enough to receive Pfizer (double vaccine) earlier in the year. Our health system, including my home town, is currently experiencing a growing number of Delta strain Covid presentations. I have been on Fingolimod since 2020 with no great issues. Wondering your thought on whether it is worth considering switching to another class of DMT?

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In general pwMS on fingolimod handle COVID-19 reasonably well. And the vaccine may give enough T-cell immunity to prevent severe infections. I am not telling any of my patients to switch unless they have other comorbidities or are old (> 55-60 years of age). Again the decision to switch is theirs, not mine I will however support them.

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Thank you so much Prof G - I look forward to growing my understanding of this MS business through your balanced and much appreciated posts. Keep well!

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School starts with students next week. As a school librarian, I am scheduling classes. My library is fairly large. I have table and chair seating for nearly 100 middle school students (age 11-14). Due to the nature of the work, I sometimes double and triple book classes - max students 75 in one class period.

I thought if the students were sitting and not moving around during class, we are all masked, many (at least in 8th grade) will be vaccinated, that I would be reducing my risk. For instance, I am only scheduling one class at a time to checkout books since students will be moving around. I also have a sink in my back office to wash my hands.

Am I mistaken? Should I only teach one class at a time (max 26 students) regardless of whether they are predominantly sitting or moving around?

I read everything I can from reputable sources and am struggling to determine what are reasonable precautions in my setting. Timing wise, I can get my 3rd dose in a couple of weeks.

But again, will the T-cells get the job done without the B-cells? Is there evidence for that or is that determination based on what should happen given scientific understanding? It seems like even after a 3rd dose, I will still need to be very cautious and make adjustments to how I schedule and teach my classes.

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I can't give you specific advice. But overall most pwMS on ocrelizumab do okay when they get COVID-19. You may have enough vaccine immunity in the T-cells to prevent you from getting severe COVID-19. I would delay the booster until you are at a stage that you are more likely to respond.

In terms of work etc. At some point, we have to learn to live and work with the virus. We can't paralyse society and the economy indefinitely. This is why the UK government has lifted all restrictions and allowing the spread of the delta variant; presumably to generate herd immunity. Sadly, there will be collateral damage and some people will get severe COVID-19 and some will die. This is the tradeoff the politicians have made. I suspect even countries like New Zealand and Australia, who have been trying to eliminate the virus, too will have to come around to living with the virus.

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Thanks for taking the time w/ this response. I am fortunate that I have a degree of autonomy and can make adjustments that won't impact instruction. It's disconcerting to go back to school with seemingly fewer protections while increasing the number of students during the rise of Delta. But, yes, I need to work - so will do the best I can. Take care.

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But you are at least in a better position than a year ago. We now have knowledge and treatments. We know the vast majority of pwMS on an anti-CD20 do okay if they get COVID-19, vaccine immunity is not zero, i.e. even if you have no antibodies you are likely to have T-cell responses that will offer some protection. The latter may be all that is required to protect you from getting severe COVID-19.

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Thank you for this thread. On Ocrevus here, 51 yo female, “preehabilitating” (!) and living in a US state w very high covid rates combined with low vaccine uptick….anxiety had gotten the best of me.

I do see glimmers of hope in all these words - very helpful as my teens head to school!

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It's not clear above - I am taking Ocrevus.

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Prof - what of the CD20 population that have already been infected? their t-cell army will be fully mobilised but any data on whether this will prevent reinfection on the basis that they will still be short of an antibody response?

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Yes, they will have reasonable T-cell immunity. But this does not necessarily prevent from being reinfected. The latter is happening in the general population.

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Yes, provided you use the anti-spike antibody results and not the anti-nucleoprotein, which is not in the majority of vaccines.

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