Immunity is for life, but you can get infected with COVID-19 if you are vaccinated but treated with anti-CD20 or fingolimod.

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Yesterday we heard that if you have not made an anti-vaccine response after two jabs, then there is a big chance that you wont after three. This work in MS confirms what we have seen in other conditions using anti-CD20. This has implications of people treated with anti-CD20 which depletes memory B cells and the cells that will make new vaccine responses, as it means that you will not have protection to prevent infection from occuring. You then have to hope your memory T cells possibly supplemented with an anti-viral will do the trip to protect you from severe infection

How long does immunity last for….You woud think a couple of months. The simple answer is it lasts for life, but the magnitude of responses will vary and this in part dependson how much you see the targets of the immune response. See it alot and the immunity may hang around and see it not alot and it will disappear but bring back the target and off it will go again but it may take a few days.

Gurevich M, Zilkha-Falb R, Sonis P, Magalashvili D, Menascu S, Flechter S, Dolev M, Mandel M, Achiron A. SARS-COV-2 Memory B and T Cells Profile in Mild COVID-19 Convalescents subjects. Int J Infect Dis. 2021:S1201-9712(21)01203-0.

Objectives: . Antiviral adaptive immunity involves memory B-(MBC) and T-cells (MTC), however their dynamics in SARS-CoV-2 convalescents warrant further investigation.

Methods: . In the cross-sectional and longitudinal study, we evaluated blood-derived MBC- and MTC-responses in 68 anti-spike IgG-positive mild-COVID-19 convalescents at visit 1 between 1-7 months (median 4.1 months) after disease onset. SARS-CoV-2 anti-spike IgG was performed by ELISA, MBC by SARS-COV-2 specific receptor binding domain (RBD) Elispot and Interferon gamma (IFNg), interleukin 2 (IL2) and IFNg+IL2 secreting MTC by IFNg and IL2 SARS-CoV-2 FluoroSpot. For 24 patients sampled at first visit, the IgG, MBC and MTC analysis were also performed 3 months later at second visit.

Results: . Seventy two percent were both MBC- and MTC-positive, 18 % – MBC-positive and MTC-negative, and 10% – MTC-positive and MBC-negative. The peak of MBC-response level was detected at 3 months after COVID-19 onset and persisted up to 7 months post infection. A significant MTC-levels were detected one month after onset in response to S1, S2_N and SNMO peptide pools. The frequency and magnitude of MTC response to SNMO (Spike, nucleocapsid, membrane and open reading frame)was higher than to S1 and S2_N. Longitudinal analysis demonstrated that even when specific humoral immunity declined, the cellular immunity persisted.

Conclusion: . Our findings demonstrate durability of adaptive cellular immunity at least for 7-months after SARS-CoV-2 infection that suggest long-lasting protection

However one imagines some of the memory may get affected by MS treatments, if that a mechanism of how they stop MS. There are two classess of drugs that inhibit antibody responses from generating. These are the anti-CD20s and the sphingosine-1-phosphate receptor modulators, notably fingolimod. When you look in the people in UK, this lack of antibody response seems to associated with an increased risk of COVID-19-related infection.

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.

Fig 2
As the blue and red lines go above the black lines it tells you when the change in risk occurs and this occurred in the time interval when people would have been vaccinated

Highlights

  • Risk of SARS-CoV-2 infection in pwMS on ocrelizumab compared to the general population is increased despite mass vaccination.
  • Risk of SARS-CoV-2 infection in pwMS on fingolimod compared to the general population is increased despite mass vaccination.
  • The risk remains the same as the general population for pwMS on other MS therapies after mass vaccination.

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.

If you can’t get the paper from the link above get the preprint here

https://assets.researchsquare.com/files/rs-1016584/v1/894a9f65-d9f3-4c7c-806a-59f5d2b9c877.pdf?c=1635290142

If you get COVID-19 and don’t make antibodies you should be eligible for one of the antibodies that neutralise infection. These work against the Wuhan and to some extent the delta strain but there are some that may not be that good for omicron

Cameroni et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. BioRXiv https://doi.org/10.1101/2021.12.12.472269

A flat line at the bottom suggests relative lack of effect.

Preprint. COI some of the authours work for VIR who work with Glaxo Smith Klein. So if you are based in UK and catch COVID sotrovimab may be useful

Importantly the effects of sotrovimab and relative lack of effect with the REGen_CoV cocktail is confirmed in this unreviewed preprint and many others.

SARS-CoV-2 Omicron variant escapes neutralization by vaccinated and convalescent sera and therapeutic monoclonal antibodiesIkemura, N., Hoshino, A., Higuchi, Y., Taminishi, S., Inaba, T., Matoba, S MEdRXiv 2021 .10.1101/2021.12.13.21267761

These preprints also show the effects of the different vaccines on their capacity to neutralise omicron. The adenoviral versions were less active than the RNA vaccines

Analysis: A meta-analysis of Early Results to predict Vaccine efficacy against OmicronKhoury, D. S., Steain, M., Triccas, J., Sigal, A., Davenport, M. P., Cromer, D. MEDRXIV 10.1101/2021.12.13.21267748 

In the studies to date, the estimated fold-drop in neutralisation titre against Omicron ranges from 2- to over 20-fold depending on the study and serum tested. Collating data results in a combined estimate of the fold drop in neutralisation titre against Omicron of 9.7 (95%CI 5.5-17.1). We use our previously established model to predict that six months after primary immunisation with an mRNA vaccine, efficacy for Omicron is estimated to have waned to around 40% against symptomatic and 80% against severe disease. A booster dose with an existing mRNA vaccine (even though it targets the ancestral spike) has the potential to raise efficacy to 86.2% (95% CI: 75.4-92.9) (symptomatic) and 98.2% (95% CI 90.9-99.7) (severe) against Omicron.

This suggests that a booster as it may help give protection as supported by numerous preprints surfacing recently

mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variantGruell, H., Vanshylla, K., Tober-Lau, P., Hillus, D., Schommers, P., Lehmann, C., Kurth, F., Sander, L. E., Klein, F.MedRXiv 10.1101/2021.12.14.21267769 

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variantGarcia-Beltran, W. F., St Denis, K. J., Hoelzemer, A., Lam, E. C., Nitido, A. D., Sheehan, M. L., Berrios, C., Ofoman, O., Chang, C. C., Hauser, B. M., Feldman, J., Gregory, D. J., Poznansky, M. C., Schmidt, A. G., Iafrate, A. J., Naranbhai, V., Balazs, A. B.10.1101/2021.12.14.21267755 

SARS-CoV-2 Omicron: reduction of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concernAggarwal, A., Ospina Stella, A., Walker, G., Akerman, A., Milogiannakis, V., Hoppe, A. C., Mathivanan, V., Fichter, C., McAllery, S., Amatayakul-Chantler, S., Roth, N., Coppola, G., Munier, M. L., Darley, D. R., Khoury, D. S., Foster, C. S. P., Lu, Y., Schofield, P., Jackson, J., Henry, J., Mazigi, O., Jaeck, H.-M., Langles, D., Cromer, D., Davenport, M. P., Christ, D., Matthews, G., Rawlinson, W., Kelleher, A. D., Turville, S. G.10.1101/2021.12.14.21267772 — Posted: 2021-12-15

And finally…A couple of weeks ago we suggested that omicron had so many unknown mutations that it could have come from animal where the virus was mutating and adapting to the animal before jumping back to humans. Whilst we pointed a finger at deer, it seems it could have been the meeces. Do you buy this idea?

Evidence for a mouse origin of the SARS-CoV-2 Omicron variantWei, C., Shan, K.-J., Wang, W., Zhang, S., Huan, Q., Qian, W.10.1101/2021.12.14.472632 — Posted: 2021-12-15

COI No relevant.

Disclaimer: This is not clinical advice and the views are those of the author and do not represent the views of any institution

About the author

MouseDoctor

27 comments

  • I have asked this before but how can you get tested as to how well you have responded to a vaccine and actually be given the results?

    Finally if you had alemtuzumab in 2013/2014 will your immune system now respond well?

    • If you had alemtuzumab in 2021 you immune system can respond well, if you had it in 2013/2014 you are no different to the rest of the general population. If you had AZ you will have made a poor response that gives minimal B cell protection against omicron if you had a recent boost you should be protected for a few months.

      As for getting tested you have to pay for a test. Unfortunately at Barts when the ethics were done there was not a provision to inform the participants which I think is a shame

  • Thank you very much for the post, MD.

    I feel like there is an undeserved lingering pessimism in the discourse surrounding anti-cd20s and covid-19. For instance, when you say we have to ”hope that our memory T cells possibly supplemented with an anti-viral will do the trip to protect us from severe infection”, I think it gives readers an idea that they are very likely going to get a severe disease course if they contract Covid-19, which – as far as I’ve come to understand – is far from true – especially in younger patients, lets say <35 years of age?
    And if in fact the vast majority of patients who are completely B-cell depleted at the time of infection recover just fine – is this most likely to be attributable to cellular immunity?
    Still waiting to see data on clinical relevance of T-cell responses on covid-19 disease courses in anti-cd20 PwMS. If i recall correctly there is approximately a 2-3x increased chance of hospitalization in anti-cd20 treated patients PRIOR to vaccination?
    It'll be interesting to see what the odds will be for hospitalization post-vaccination in the same group of PwMS that did in fact have robust T-cell responses and three/four jabs.
    Again thanks alot for the updates.

    • No I dont think you are in for a severe ride…especially if you have been vaccinated, but you may be hospitalized. It is happening, but people are recvoering and as I have said and written you can do OK without any B cells. I just don’t know what will happen and will find out by reading.
      However, this is why you need a pulse oximeter to check your O2 saturations and if it drops below 90% get on the blower to 111….tell them you are on immmunosuppression and may be eligble for antivirals

  • Thanks for the info.

    Bottom line, if you are on Fingolimod, for 2 years now you only hear bad news. And as time goes by, news become even worse. Firstly, we had been waiting for the vaccine, after the jab didn’t work, we crossed-fingers about T-cell antibodies existence. Then, the booster dose was offered and again we tried to survive every day hoping that we ‘ll gain some protection. After that, neutralizing antibodies infection showed up like a “life-saver” solution for those that do not seroconvert, but now with Omicron variant, even this hope disappears. And time goes by and pwMS on fingolimod try to live in a protected bubble, trapped between the monster of covid and the fear of rebound effect.

    So, maybe it’s time for the MS specialists to consider on how fingolimod patients can be released from their nightmare and manage to live again like normal people. How we can go to our work, see our families and our friends or even go to a restaurant just for fun. For 2 years’ time, my only thought is how to survive and not how to live normally. Novartis does not even bother to make a statement or something about their prison-like medication and what I only hear and read from MS professionals is “continue on your treatment, there is nothing to do” and “take the jab”. Nice suggestions, but is there anything more useful?

    • Even this hope disappears no one of the two UK anti-viral antibodies is unaffected so keep the hope alive. I agree the companies have done little to inform I think fingolimod treated individuals are most in the dark.

      • Thanks MD.
        I’m on Fingolimod & tested positive for COVID a few weeks back. My symptoms were very mild & thankfully I had no major issues. My question is, have I developed some level of immunity / protection having had the virus ?

  • Not a medical immune MS scientist here, but I’ve been watching this here and on the Facebook Ocrevus sites, and TV, since onset. TV ads by Roche say nothing and imply, using actors without masks, that everything can get back to almost normal with O. The Facebook sites are posted in part by newbies to O, getting their 1st infusion and describing their hopes for normalcy. If you talk about covid there, you are warned and then your posts are removed. I was on O and stopped early on as the pandemic hit Italy. I did it on my own accord as MS Doc was on sabbatical. I live in “Ground Zero” for the “proud unvaxxed”. Perhaps 5% of people here in PA USA are masked, including food workers and everyone else. I am 64 with a number of “maybe, not quite, you’re OK” premorbidities, and don’t you think I am happy as hell to not be on Ocrevus any more? There are alternatives if I need them but at 64 I’m doing well enough, certainly not in denial or walking around afraid, hoping for a T cell response or hospital treatment if I need it.

    The whole thing is fascinating. I’ll keep speaking out until Roche and others address the subject specifically so newbies know the mystery and uncertainty of what they are getting into. If you told them of cancer risks with the same odds as covid, would they have gone on O? And what will covid do next? I’m still waiting for herd immunity but I got my life back, to keep me company while I’m still waiting.

    • now there’s a thought, in the interests of transparency perhaps Roche et al could inform neurologists who have prescribed their drugs what may be of some interest to their patients?

      • Yes, after 2 years I am acutely aware of my self imposed anticd20 prison. How about the US CDC gets balls and gives real guidelines for management of immune compromised other than immune compromised should stay home if community spread is high? And CDC should untie the hands of US drs to permit antibody testing of the vaccinated immune compromised.

        • They should have just finished a trial looking at mycofenylate, rituximab methotrexate but sadly they did nothing about modifying the any CD20 compared to the others with delayed dosing. What will they learn by the study…for anti-CD20 very little I suspect and the booster dosing oportunity has been wasted

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