MS COVID19 infection and third boosters


Symptomatic infection in CD20/Fingolimod vaccinated individuals

More info on MSers gettig COVID-19 and in this study those vaccinate and getting MS were teated with anti-CD20 (ocrelizumab) and fingolimod. This is biology. These two agents are notable because they block antibody responsiveness and it is antibody levels that protect you from infection. To date people have faired reasonably well. If you didnt get a boost and you encounter omicron there is not enough antibody to stop it infecting is didnt get an RNA vaccine and if you did, in most people there is not enough antibody and ad in most people it wanes with time and so there is not enough antibody. Getting an RNA boost will give you protection for a while, but if you have anti-CD20 or finolimod you are going to be at risk from infection.

Rose DR, Mahadeen AZ, Carlson AK, Planchon SM, Sedlak J, Husak S, Bermel RA, Cohen JA, Moss BP. Clinical features and outcomes of COVID-19 despite SARS-CoV-2 vaccination in people with multiple sclerosis. Mult Scler J Exp Transl Clin. 2021 Nov 26;7(4):20552173211057110.

Background: Several studies have demonstrated reduced serological response to vaccines in patients treated with anti-CD20 agents. However, limited data exist surrounding the clinical effect of disease modifying therapy (DMT) use on vaccine efficacy. Objectives: To investigate breakthrough coronavirus disease 2019 (COVID-19) in vaccinated people with multiple sclerosis (PwMS) on DMT.

Methods: PwMS on DMT diagnosed with COVID-19 after full vaccination were identified from an existing Cleveland Clinic COVID-19 registry, supplemented by provider-identified cases. Demographics, disease history, DMTs, comorbidities, exposures, vaccination status, and COVID-19 outcomes were confirmed by review of the electronic medical record.

Results: Thirteen (3.8%) of 344 fully vaccinated people with multiple sclerosis on disease modifying therapy were diagnosed with COVID-19 after vaccination. Ten patients (76.9%) were on an anti-CD20 therapy, the remaining 3 (23.1%) on fingolimod. Only 2 patients (15.4%), both on anti-CD20 therapy, required hospitalization and steroid treatment. Neither required Intensive Care Unit admission.

Conclusion: Patients treated with anti-CD20 agents and sphingosine 1-phosphate receptor modulators may still be at risk for COVID-19 despite vaccination. While still at risk for hospitalization, intubation and death from COVID-19 appear rare. Larger studies analyzing how this may differ in the setting of emerging variants are needed.

Another CD20-depletion story but you make more T cell responses with a Booster

The people in the first study delayed rituximab. The ones that didnt make a response ranged from a 5-24 months delay and those that did had a 6-24 mo.nth delay but the middle figure was 7 for the non-responders and 21 for the responders. However ocrelizumab is a better depleter than rituximab. I guess this further supports our idea that at 6 monthly dosing there is more than is needed and so a study needs to be done. It also further indicates that being vaccinated within 6 months of infusion runs a risk of no antibody response. But what to do in the time of omicron, It is not my job to comment but ProfG has said what he has consistently said in a period of high infection risk.

In the paper below it offers some good news.

Determining the best window for BNT162b2 mRNA vaccination for SARS-CoV-2 in patients with multiple sclerosis receiving anti-CD20 therapy. Rico A, Ninove L, Maarouf A, Boutiere C, Durozard P, Demortiere S, Saba Villarroel PM, Amroun A, Fourié T, de Lamballerie X, Pelletier J, Audoin B.Mult Scler J Exp Transl Clin. 2021 Nov 29;7(4):20552173211062142. doi: 10.1177/20552173211062142

We studied the serologic response to the BNT162b2 mRNA vaccine at four weeks after the second dose in patients with RRMS treated with rituximab with extended-interval dosing (n = 26). At four weeks, 73% of patients were seropositive. No patient without B cells at the first dose (n = 4) was seropositive. Four of seven (57%) patients with B-cell proportion >0% and ≤5% were seropositive. All patients with B-cell proportion >5% (n = 15) were seropositive. In all patients, quantitative ELISA measures after vaccination were correlated with B-cell counts measured before vaccination. In patients receiving rituximab, seropositivity after BNT162b2 mRNA vaccination emerged only after B-cell repopulation.

The mean time to surpass 1% B-cell proportion after anti-CD20 infusion is 250 days (eight months),

However, there is some good news

Omicron-specific cytotoxic T-cell responses are boosted following a third dose of mRNA COVID-19 vaccine in anti-CD20-treated multiple sclerosis patientsMadelon, N., Heikkila, N., Sabater Royo, I., Fontannaz, P., Breville, G., Lauper, K., Goldstein, R., Grifoni, A., Sette, A., Siegrist, C.-A., Finckh, A., Lalive, P. H., Didierlaurent, A. M., Eberhardt, C. S.10.1101/2021.12.20.21268128 

Importance: The SARS-CoV-2 variant Omicron escapes neutralizing antibody responses elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third dose of vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. Objective: To determine T-cell responses to the Spike (S)-protein of Omicron in anti-CD20 treated patients before and after their third mRNA COVID-19 vaccination

Design: Prospective observational monocentric study

Setting: Conducted since March 2021 at the University Hospital Geneva Participants: Twenty adults with multiple sclerosis on anti-CD20 treatment (ocrelizumab) who received their third dose of mRNA COVID-19 vaccine 6 to 7 months after their second vaccination.

Intervention: Blood sampling before and one month after the third vaccine dose Main outcomes and measures: Quantification of CD4 and CD8 (cytotoxic) T cells specific for SARS-CoV-2 S-protein of vaccine strain, Delta and Omicron variants , using activation marker induced assay (AIM) and comparing frequencies before and after the third vaccine dose.

Results: S-specific CD4 and CD8 T-cell memory against all variants was maintained in around half of the patients six months after their second vaccination, albeit at lower frequencies against Delta and Omicron variants. A third dose enhanced the number of responders to all variants and significantly increased CD8 T-cell responses. The frequencies of T cells specific to Omicron and Delta remained lower than those specific to the vaccine strain after the boost.

Conclusion and relevance: Vaccinated MS patients on anti-CD20 treatment show robust T-cell responses that recognize S from the circulating Delta and Omicron variants. Response rates increased after the third dose, demonstrating that a booster dose might improve cytotoxic T-cell mediated protection against severe disease in patients with low humoral response. The clinical relevance of the reduced frequencies of T cells specific to Omicron will need to be monitored in the future.

So what is going to happen when you encounter the SARS CoV2 virus. T cells wont stop you getting infected unlike antibody but they may limit symptomatic disease. We don’t know what will happen in the UK, in South Africa news has been promising but there the population is younger and many people have been naturally infected. Although it has been said that “Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron
infection, suggesting at most limited changes in severity compared with Delta”. (ferguson et al Imperial Colege report 49) says “ This does not say that delta and omicron are the same.

Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South AfricaWolter, N., Jassat, W., Walaza, S., Welch, R., Moultrie, H., Groome, M., Amoako, D. G., Everatt, J., Bhiman, J. N., Scheepers, C., Tebeila, N., Chiwandire, N., du Plessis, M., Govender, N., Ismail, A., Glass, A., Mlisana, K., Stevens, W., Treurnicht, F. K., Makatini, Z., Hsiao, N.-y., Parboosing, R., Wadula, J., Hussey, H., Davies, M.-A., Boulle, A., von Gottberg, A., Cohen, C.10.1101/2021.12.21.21268116

Background The SARS-CoV-2 Omicron variant of concern (VOC) almost completely replaced other variants in South Africa during November 2021, and was associated with a rapid increase in COVID-19 cases.

Results From 1 October through 6 December 2021, 161,328 COVID-19 cases were reported nationally; 38,282 were tested and 29,721 SGTF infections were identified. The proportion of SGTF infections increased from 3% in early October (week 39) to 98% in early December (week 48). After controlling for factors associated with hospitalisation, individuals with SGTF infection had lower odds of being admitted to hospital compared to non-SGTF infections (adjusted odds ratio (aOR) 0.2, 95% confidence interval (CI) 0.1-0.3). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ between SGTF-infected individuals compared to non-SGTF individuals diagnosed during the same time period (aOR 0.7, 95% CI 0.3-1.4). Compared to earlier Delta infections, after controlling for factors associated with severe disease, SGTF-infected individuals had a lower odds of severe disease (aOR 0.3, 95% CI 0.2-0.6).

Conclusion Early analyses suggest a reduced risk of hospitalisation among SGTF-infected individuals when compared to non-SGTF infected individuals in the same time period, and a reduced risk of severe disease when compared to earlier Delta-infected individuals. Some of this reducton is likely a result of high population immunity.

Increased risk of infection with SARS-CoV-2 Omicron compared to Delta in vaccinated and previously infected individuals, the Netherlands, 22 November to 19 December 2021Eggink, D., Andeweg, S. P., Vennema, H., van Maarseveen, N., Vermaas, K., Vlaemynck, B., Schepers, R., van Gageldonk-Lafeber, A. B., van den Hof, S., Reusken, C. B. E. M., Knol, M. J.10.1101/2021.12.20.21268121

CoI Non relevant

Disclaimer: These are the views of the author and not advice or represent the view of any institution

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    December 22, 2021 at 12:20
    Not sure any conclusion can be drawn from a sample size of 13.

    There have been 276m cases worldwide that we know of.
    Even in the sunniest countries, MS prevalence is about 1/1000 so that means at the very least 276,000 MSers have had Covid in some form – by probably closer to 500,000.
    Even if only 10% of MS patients are on CD20 therapy – and it’s probably way more – that’s at least 27,600 worldwide and likely more than double that. It would be nice if even a small proportion of their case histories were being collated so researchers could try to understand the interplay between Covid, MS and DMTs…

    December 22, 2021 at 12:55
    Granted this is a tiny group but if my math is right 20% of those on anti cd 20 who got covid needed hospitalization. That doesn’t seem low or insignificant?

    • Dear Dan
      No it isn’t…but perhaps I thought wrong that this information may be releventto some people.
      As for unsubscribing “I’ve no idea how you unsubscribe….” perhaps when there is a re-skin I can ask computer bod about this, but I guess you can direct to Junk, but fear not the COVID posts will diminish soon as will my other posts, when ProfG left I agreed to keep posts going at the current rate but not for much longer.

      • MD1 – “but fear not the COVID posts will diminish soon as will my other posts”………I hope this means the rate you post to the blog (in the future) will diminish. Please do not tell me you intend to pull a G and just delete all your old/previous posts…007 style. If so, I need to buy some more printer ink!

        P.S. The majority of individuals greatly appreciate all of the hard work and dedication you put into this blog. I cannot stress how important and lifesaving this blog has been for me, even if not every post is relevant to my situation. So, screw the haters, you just keep doing you MD1.

        • No do this and couldn’t even if I wanted to….we do not have the passwords to be able to do this. There is a plan to remove the control the control from ProfG and the administrator who programmed the blog we know where everything is. However, I think the frequency needs to be reduced

  • i put this on Prof G ms selfie…maybe doc M can comment? fits in the geneva findings?

    says that boosters give very good cd8+ t-cell protection in mouse model.

    another research tells us that cd20 treated persons anyway seem to have a higher cd8+ reaction on vaccines than non treated.

    so if we combine that and see that b-cell antibodies cant win against omicron is it wrong to say that cd20 treated might even have a somehow „better“ protection against omicron after the booster?

  • Dear MD,
    I just caught Covid at the end of november. I am also a patient on anti-CD-20 (Rituximab).I have been three times vaccinated since october. I had really mild symptoms and wouldn’t have even noticed my infection, if i had not tested myself just to be sure. After 7 days of slight symptoms like a running nose and sore throat I was symptom-free.

    Am I at great risk catching covid and having a severe outcome? Is there some data on second infections in CD-20 depleted individuals?

    • This may be what we want with omicron if that is what you had the symptoms may be mild and therefore you could say the boostered did the trick and this will be the case for many people and this is perhaps where you have to think what are your risks how many comorbidities do you have. I suspect if you have had a mild infection iy will be mild next time, but as you age this may change as you take on age related comorbidities. There are cases not in MS of a worse second infection but that was rare.

  • Hi MD and thank you for your post. Do you or your colleagues know if there’s a way of managing vaccines and CD20 therapy – possible switch to ? – a DMT that you the vaccine will work better and give you protection. Or wait between treatments & this would need to be properly managed, as bloods help know when & if okay to vaccinate (has the patient developed high levels of antibody). What is the optimal infusion time-line, there should be a rough guideline. This could be sent out to all Neuros to speak to their patients and discuss a plan. This shouldn’t be left to pwMS who are usually unwell & in particular feeling a bit stressed at the moment, with how prevalent this Omicron is. If this info is then digested & the pwMS can make a decision (along with support from their MS team/Neuro) as to how to go forward with their treatment and vaccines. We can’t just expect everyone to be onboard with reading the dreadful difficulties with being immune suppressed & to stay in our homes for the foreseeable future. This needs to be properly managed & conversations about the this should be happening now – not when you’ve had an infusion (& you’re so grateful for this also, I might add). TIME – is not our sides and it is too late to shut the door, when the horse has bolted!

    Sorry, to be a bit stressy about this – as you can imagine, each day that goes by is a potential threat to anyone on treatment or with progressive MS, if they catch this blinking virus!

    On a happier note, Merry Christmas everyone and try and enjoy some of the festivities, whatever you get up to!

    • I am not a neuro and so cant make any recomendations…but one could ask if you are starting today would you go down the S1P1 anti-CD20 route and which one would you choose. As I said when you start a treatment you neeed to think what next if drugs fail…For both ocrelizumab and fingolimod even if you stop and switch to something else they are both going to maintain an influence for some time and for ocrelizumab this is months to over a year. I heard that when COVID arrived some neuros switched fingolimod to other S1P1 modulators as some may be more quickly reversible. I have opinions of what I would do but I cant say what this would be.

  • My st experts predicted that SARS COV-2 would evolve to be more transmissible yet less virulent. For killing your host is an evolutionary dead-end. Data indicates vaccines prevent severe disease and hospitalization by not only humoral but cellular immunity. Those on anti CD 20 therapies will need boosters to maintain their cellular immunity.

    • The info is there but after two the T cell response is perhaps better if you dont have B cell response, is it loss of B regs. If the people look at the severity of the vaccinated then you have your answer, but what disappoints me is that this isse has not been resolved, it could and should have been done already but playing catch-up all the time has moved us nowhere maybe lucky we have anti-virals coming, although they will select resistant bugs.

  • I decided to stop Ocrevus and b cells are recovered so far. So I’m ready for the booster jab. Does anybody know when the protection kicks in after boostering? And, secondly, what happens to the antibodies if I go back to Ocrevus in, let’s say, a month or two?

  • Merry Christmas and All the best in 2022 ! Thanks for all the fantastic information that you provided this year.
    We need this information, and it’s much appreciated.

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