58 Comments

Hello Professor Giovannoni, regarding your comment about being on the shielding list, should people on Ocrelizimab be on the shielding list?

I ask because I have never been asked to shield. I contacted my GP surgery when the government announced that more people were being added to the list and letters were being sent, and was told they don't add people to the list. I then contacted my MS nurse and was told that I should avoid going to the shops and follow social distancing and hand washing, but no need to sheild. My neurologist also listed obesity on my record so was surprised that I wasn't on the list, I am 49 too, so perhaps considered less of a risk.

I had my 3rd vaccine on the 1st October, which I only got as I challenged the advice I was given not to delay my infusion for the covid vaccine , my next infusion was due that month too. The Royal London then booked me in for my last infusion on the 7th December. I understand that I should now have a 4th vaccine (booster) 3 months after my last which would be the 1st January, but that would be 3 weeks after my infusion. I'm not sure on the time delay between infusion and the booster. Do I need to leave a bigger window or is it advisable to get this done as soon as possible around the 1st?

Having read a previous article of yours I have bought an oximeter, so thank you for that.

Kind regards

Rachel

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Rachel, regarding the timing of the booster there is no right or wrong answer. To be honest this is one situation were knowing if you have seroconverted would help. The reason is booster response when you have B-cell memory are relatively intact on ocrelizumab. However, if you don't have anti-SARS-CoV-2 spike antibodies then to maximize your chances of getting an antibody response you have to wait for some B-cell reconstitution which takes on average 9 months. However, when you are in the eye of the storm it is probably worth getting your booster done ASAP to boost your T-cell responses.

I want to reassure you that it is the same predictors for poor outcome from COVID-19 in ocrelizumab treated patients as in the general population, i.e. age and comorbidity and in the case of MS physical disability.

Please note that if you ask another HCP you may get different advice to this. As with most things COVID-related there is rarely a consensus among HCPs

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I think the term shielding is a misnomer and should now be referred to as the vulnerable list. Yes, pwMS on anti-CD20 (ocrelizumab, ofatumumab, rituximab) and the S1P modulators (fingolimod, siponimod, ozanimod, ponesimod) should be on the vulnerable list. This should also include people recently treated with alemtuzumab or recently had HSCT.

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Thank you so much for your response.

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I just recovered from covid. Inevitable. Everyone in London I know has it right now! Luckily it wasnt as bad as I thought it would be considering no vaccine response and I think I got away pretty unscathed. Apart from my neck glands are bloody sore still, 2 weeks on.. Now I’m wondering, I guess I’ll have some antibodies. How long will these last for? I read on gov website something like 90 days? Booster due in Feb due to timing with next Ocrevus infusion (to be delayed..) . Am I likely to get reinfected like, before 90 days? Is that possible?!

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I don't think anyone really knows. I *suspect* reinfection to likely be possible given that without B-cells there are unlikely any antibodies preventing it. T-cells should be better at fighting the infection, though.

But I am no doctor and certainly no immunologist.

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I had a Hot MS clinic appointment yesterday re a suspected relapse. The neurologist I saw told me that the data for Ocrevus and covid is being monitored for quite a while now and it’s looking very good. She encouraged me to go back on to Ocrevus. I’m really confused about this.

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Yes, people on ocrelizumab or other anti-CD20 therapies have a 2.0-2.5x greater risk of getting COVID-19, severe COVID-19, needing intensive care admission and are likely to have a higher risk of dying from COVID-19 (5-6% mortality, published mortality). The mortality however is driven by age, comorbidities and disability.

People on ocrelizumab don't make very good antibody responses to the COVID-19 vaccines and therefore are likely to be at high risk of Omicron.

In the UK ocrelizumab-treated patients are considered vulnerable and are hence eligible for anti-SARS-CoV-2 antivirals. We are also advising increased vigilance, strict social distancing, prehabilitation, pulse oximetry, etc. and #GettingVaccinatedASAP or #GettingBoostedNow.

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Hi Dr G,

Hope you are safe and well. Thank you for an excellent update. I was hoping you could clarify for me: are *all* pwMS eligible for these new community based treatments should we contract covid? I am not on a DMT at present, as my Neurologist took the decision to hold off on starting Rituximab until things improved with the pandemic. The MS Society website seems to suggest we are all eligible based on our diagnosis of MS but I wasn't sure if that alone classified us as vulnerable. I wasn't added to the shielding list before, so I am not sure. I live in Scotland.

Many thanks,

Jen

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The Government's list says people with MS, and that is all people with MS, are vulnerable and should be on the shielding list. However, this is really not the case. In people with low levels of disability on DMTs it is only those on anti-CD20 therapies, S1P modulators and those recently treated with alemtuzumab and HSCT that need to be on the list. The other DMTs are not associated with a higher risk of COVID-19, severe COVID-19 or potentially death.

In older more advanced pwMS what drives vulnerability are other factors and the call here depends on individual factors. This is why Oxford's Q-COVID COVID-19 risk calculator is useful to assess your risk.

https://qcovid.org/

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Thank you so much for clarifying. Take care and have a wonderful, safe Christmas. 🎅🎄☃️

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What I am totally confused about is why all countries are not treating and vaccinating people the same way. Here in the USA, if you had the first 2 jabs of Phizer or Moderna vaccine you were considered "fully vaccinated and had to fight to get a 3rd "booster" shot. The 3rd shot of Moderna here is a half dose. I had the Phizer so I got a full dose on the 3rd shot. Now in a few months if i went to get a 4th shot, they would turn me away. At least as it stand now because that's how its set up up here right now. There is no 4th shot as a booster thing.. They are saying the 3rd shot is the booster. If "they" decide we will need an annual shot to keep the immunity levels up then that will be "their" choice, not ours.. I don't understand.

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The reason is that every country has their own experts interpreting data in different ways. In addition, when the evidence base or data is incomplete you get expert opinion and we know experts rarely agree with each other :-(

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Hi, I would be very grateful for your advice. I last had an Ocrevus infusion in March, and had my first 2 Covid vaccines in January and February, with a 3rd in September, and am due to have a booster at the end of December.

However, I am 11 weeks pregnant and know that I am at risk of more severe Covid as a result…and that I probably don’t have any antibodies from the vaccine doses so far. If I were to get Covid am I right in thinking that the anti viral sotrovimab would be option as it has been used for pregnant women in other countries it looks like? How would I be able to access this medicine if I needed to…would I have to make sure I had highlighted the potential of this scenario to my GP prior, or is it something my neurologist at the Royal London would be able to arrange?

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Clare, I assume the same criteria would apply for sotrovimab as those currently in place for Ronapreve. You have to have swab positive COVID-19, be antibody negative, be vulnerable (you are because of ocrelizumab and being pregnant) and need hospitalisation.

Please note when a new product is launched into the NHS there are supply and distribution issues and hence sotrovimab may not be available across the NHS simultaneously. The same happened for Ronapreve.

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Thank you very much for responding to me, and so promptly!

I have had a look at the criteria for Ronapreve as listed in your post from a few weeks ago (https://gavingiovannoni.substack.com/p/case-study-pulse-oximetry?justPublished=true)

In regards to the antibody test, is this the NHS one you can request on the NHS website and return by post, or is it a specific one that would be done at a hospital?

Also, from what I understand from

reading around (the internet) about Sotrovimab, it seems that it is most effective if administered within the first 5 days of COVID infection, so not for someone who has been hospitalised. Considering this, I’m guessing I need to take your advice regarding the protocol for Molnupiravir, and make sure that I am correctly listed as being clinically extremely vulnerable with my GP and any subsequent government lists.

Your Twitter and blog page are absolutely invaluable, particularly during this time! I just feel like the government should be making this information much more readily available for immunosuppressed patients. It worries me that there are many immunosuppressed patients out there who are going to struggle to find out this information, and to put any necessary precautions into action. Again thank you so much for taking the time to inform the MS community!

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Re: "..reading around (the internet) about Sotrovimab, it seems that it is most effective if administered within the first 5 days of COVID infection.."

Yes, all these treatments work best the earlier they are given. I suspect the hurdles that have been put in place is to ration a short supply of the treatments and to target them to the most vulnerable.

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Thanks for coming back to me to again!

Just to let you know, and other MSers in the UK, I have received a government email this afternoon saying that I will most likely be eligible for the anti viral drugs, and that NHS track and trace will be sending me a PCR test to keep at home in case I develop any COVID symptoms and need a test to be sent off ASAP. It looks like I have been sent this email because I was on the original shielding list.

Furthermore, looking at the eligibility for the anti viral drugs, it appears that all people with MS could potentially be considered, not just those on anti cd20 therapies and s1p modulators? Let me know if I am interpreting this wrongly:

(2nd bullet point - a rare condition affecting the brain and nerves inc. multiple sclerosis.)

https://www.nhs.uk/conditions/coronavirus-covid-19/treatments-for-coronavirus/

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Please today's update on the NHS COVID-19 treatment website:

https://www.nhs.uk/conditions/coronavirus-covid-19/treatments-for-coronavirus/

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Re: "In regards to the antibody test, is this the NHS one you can request on the NHS website and return by post, or is it a specific one that would be done at a hospital?"

I think any assay that is done in an NHS lab would be acceptable. Saying that I would be surprised if any responsible clinician would ignore an test result that has not be done via their own labs. This is why we have accredited laboratory system so we can trust their results without having to repeat them

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I have SPMS,have had two jabs ( feb and may ) feel that I have gone downhill after each jab and late October have had a relapse and not got better ( my first in many years). Ten days ago I got COVID ( moderate) am anxious about having the booster as I can’t imagine being worse than I am now.( balance issues,weakness brain fog, fatigue weakness etc ) will the fact that I’ve just had COVID, ( sure it was delta due to lack of taste and smell )protect me from omicron ?

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it's my understanding that becuase these are 2 different strains of the virus, that its possible to get back to back infections, however, it;s also possible that your immune system has now built antibodies and will recognize the virus regardless of which strain it is and be able to fight it off. On the other hand, I am unsure of anywhere you could even go to get a vaccine within 90 of having COVID of either strain.. I think one of the questions on the form they have you fill out is whether or not you have had COVID or COVID like symptoms in the last 90 days

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Carol, when does a variant become a strain? What is important is that immunity to SARS-CoV-2 induced by the vaccine or earlier strains (Wuhan, alpha, beta and delta) is cross-reactive, but entirely. So you can get infected again with the Omicron variant and if you do the infection is likely to be mild. It is evident that the higher your antibody levels are the better protected you are. This is why I would recommend having the booster.

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On ocrelizumab and i am afraid i can only get one booster as the vaccination program is terrible in the Netherlands. I timed my irst 2vjabs well and got some antibodies last august. So It made sense ti me to plan my booster for my infusion in February. Now I am in doubt even about taking ocrelizumab as this seems to do nothing for my non active ppms. Is there any stuff out there on declining antibodies after being vaccinated with AZ?

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Paul, I think I have addressed why you should have the booster above. The higher your antibody levels the better your protection against Omicron and severe disease. Delaying or missing your next ocrelizumab infusion is a moot point and should be discussed with your HCPs.

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Thank you for this. We are getting no advice regarding Covid-19 vaccines and anti-CD20 treatment from our local MS clinic--so much appreciated.

A question from my PwMS: he would like to know if getting his Ocrelizumab infusion itself lowers his immune system's ability to fight off Omicron or other variants and should one delay treatment for that reason if one has been receiving Ocrelizumab for more than 2 years?

My PwMS managed to get his third full Covid vaccine (Moderna) this month at 7 months after his last infusion and is currently scheduled to get his next infusion in January at 8 months since previous infusion. Would there be any protective value in delaying the infusion further? We are currently have an outbreak of Omicron in our area.

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Re: "My PwMS managed to get his third full Covid vaccine (Moderna) this month at 7 months after his last infusion and is currently scheduled to get his next infusion in January at 8 months since previous infusion. Would there be any protective value in delaying the infusion further? We are currently have an outbreak of Omicron in our area."

Based on the Norwegian study your pwMS has about a 50% chance of having seroconverted. I am not sure delaying the next dose of ocrelizumab is going to do anything in terms of his existing B-cell responses. It will blunt future responses. Please note the emergence of treatments for COVID-19 has changed the risk-benefit ratio provided he has access to these treatments if he should develop COVID-19.

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Re: "he would like to know if getting his Ocrelizumab infusion itself lowers his immune system's ability to fight off Omicron or other variants and should one delay treatment for that reason if one has been receiving Ocrelizumab for more than 2 years?"

Yes, being on an anti-CD20 such as ocrelizumab does lower your immune systems response to COVID-19. As a result people on ocrelizumab have double the risk of being admitted to hospital and needing intensive care as pwMS not on ocrelizumab. I suspect there is also a greater chance of dying from COVID-19 as well.

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Fantastic update as always however could you answer a few questions for me.

You mention Oral Molnupiravir (Lagevrio) as being still fairly effective and being dispensed by GPS in the community but they recently approved and more effective

sotrovimab (Xevudy is accessed how? You say it is very effective but is that only offered once in hospital or is it again set to be dispensed within the community by a GP?

As a wheelchair bound woman with progressive MS who relies heavily on their partner as an unpaid carer would a carer be eligible for all these treatments?

Finally regarding South Africa, while you say they are a younger population hence why they are dealing with omicron better, are there not a lot of people with HIV therefore immunosuppressed?.

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Re: "Finally regarding South Africa, while you say they are a younger population hence why they are dealing with omicron better, are there not a lot of people with HIV therefore immunosuppressed?"

Yes and no. People with HIV on anti-retrovirals have been shown not to be immunosuppressed and do as well as normal people when they get COVID-19. However, undiagnosed HIV patients with low T-cell counts will be immunosuppressed, but the numbers of these types of people will be low and may have already succumbed to the virus in the first three waves of COVID-19.

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Re: "As a wheelchair bound woman with progressive MS who relies heavily on their partner as an unpaid carer would a carer be eligible for all these treatments?"

Yes, you would be. MS is on the list of vulnerable people and hence you can argue you should get these treatments. To the best of my knowledge sotrovimab will only be available for hospitalized patients.

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Thank you for the reply but just to clarify are you saying that my carer should be eligible for the treatment as I rely so heavily on them or him as it is my partner

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Re: "... my carer should be eligible for the treatment as I rely so heavily on them or him as it is my partner.."

I am not sure about this I was referring to the person with MS. But I see no reason why carers, and healthcare workers in general, should not be considered vulnerable when they are looking after vulnerable people.

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Important information, thank you!

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It's been 8 months since Covid-19 infection (mild case), 5 months since Astra-Zeneca vaccination, and 6 weeks since rituximab infusion.

The Covid and the vaccination were over a year after the previous rituximab dose, so there was a vaccine response.

A Pfizer vaccine booster is available now: Will it be better then to take it right away? Rather than delaying till cd-20 reconstitution.

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I've now had 3 covid vaccines but still no sign of b-cell antibodies. I delayed my 4th ocrevus infusion in October and, on the advice of my neurologist, I am now set to have it on the 30th December. I'm really concerned - do you think I would be better delaying this?

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Julie, are you eligible for the booster? You need three months between your 3rd dose and the booster. In your case because of the eminent timing of the booster it would make sense waiting for the booster (4th dose) and having the next ocrelizumab infusion 3-4 weeks later. You are an example, why advice regarding the vaccine and treatment needs to be personalized.

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Thankyou for your reply Prof G - I truly appreciate it.

I had my 3rd vaccine on 5th October - so 3 calendar months will be 5th Jan (a week after I'm currently set to have the 4th ocrevus)

I'll send your advice to my GP/ neurologist/ MS Nurse and ask to have the covid booster early in January and postpone the 4th Ocrevus until 4 weeks later.

Hope the NHS can accommodate this!

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Julie, please note that not all HCPs will agree with my advice. So you need to be prepared to argue your case.

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Hello Prof - are there any studies yet regarding breakthrough covid of vaccinated CD20 patients?

do you think that a 3rd pfizer jab protects more than just two when we talk about t-cell shield? thought that t-cell last much longer - are they „higher“ primed by the 3rd shot?

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Re: "do you think that a 3rd pfizer jab protects more than just two when we talk about t-cell shield? thought that t-cell last much longer - are they „higher“ primed by the 3rd shot?"

Yes, I do. T-cell memory is similar to B-cell memory and can wane with time. So having a booster will increase your T-cell memory and offer you extra protection.

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Re: "are there any studies yet regarding breakthrough covid of vaccinated CD20 patients? "

Yes, the study below is the first evidence, albeit indirect, the in ocrelizumab treated pwMS the vaccines don't protect against getting COVID-19. What is not known is whether or not they protect against severe COVID-19 or death.

Garjani A, Patel S, Bharkhada D, Rashid W, Coles A, Law GR, Evangelou N. Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England. Mult Scler Relat Disord. 2021 Dec 5;57:103458. doi: 10.1016/j.msard.2021.103458. Epub ahead of print. PMID: 34896876; PMCID: PMC8645279.

Background: Contradicting assumptions have been made about the effectiveness of SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) receiving immunomodulatory disease-modifying therapies (DMTs) based on the quantification of humoral and cellular immune responses. This study aimed to understand changes in the risk of SARS-CoV-2 infection among the total population of patients receiving MS DMTs in England following mass vaccination.

Methods: This is a retrospective analysis of national data collected prospectively and longitudinally. National Health Service (NHS) England and NHS Improvement (NHSE/I) hold prescribing data on all commissioned MS DMTs in England. United Kingdom Health Security Agency (UKHSA) has been collecting data on all registered SARS-CoV-2 test results, including polymerase chain reaction and rapid antigen tests. All patients receiving MS DMTs were identified using NHSE/I datasets. All patients receiving MS DMTs with SARS-CoV-2 infection (i.e., positive test) from March 2020 to August 2021 were identified by merging NHSE/I and UKHSA datasets. Similar data for the general population were captured using publicly available datasets of the United Kingdom government. The incidence rate ratios (IRR) of SARS-CoV-2 infection among patients receiving MS DMTs compared to the general population during the pre-vaccination (November 2020 to January 2021) and post-vaccination (June to August 2021) periods were calculated.

Results: A mean (standard deviation) of 41,208 (4,301) patients received an MS DMT in England during each month from March 2020 to August 2021. The IRR (95% confidence interval) of infection in patients taking ocrelizumab versus the general population increased from 1.13 (0.97-1.31) during the pre-vaccination period to 1.79 (1.57-2.03) during the post-vaccination period. For patients on fingolimod, it increased from 0.87 (0.73-1.02) to 1.40 (1.20-1.63) during the same periods. There were no significant changes for patients on other MS DMTs.

Conclusion: SARS-CoV-2 vaccines offer less protection against infection to patients taking ocrelizumab or fingolimod, who have an impaired immune response to vaccines, than the general population. These findings will have implications for vaccination policies.

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What is your advice re a 4th dose - do people on anti-CD20 count for this?

My ‘booster’ (so my third dose) was on Sept 20th so I think I’m eligible for my 4th now

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In the UK if you are on an anti-CD20 your 3rd dose is just that a 3rd dose as part of your primary vaccination and you would be eligible for a booster 3 months later.

Please read my previous Newsletter on this issue:

https://gavingiovannoni.substack.com/p/ocrelizumab-and-the-3rd-dose-of-the

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Re incubation time omicron is 5 to 7 days, at what point will LFT likely detect? Or is that a 'how long is a piece of string' question as depends on initial viral load?

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Exactly. Not sure by how much Omicron evades the LFTs yet. I suspect they work less well with Omicron as they are based on the spike protein.

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I defo got it on a Saturday and tested positive on LTF on the Friday.

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But you could still have Delta. About 50% of cases are still Delta.

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