#MSCOVID-What I we learnt…Yep I’ve had enough of this too.

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In the report below there is a view of what we have learnt about COVID-19 and MS. I guess anyone could have written this as you have probably heard about all this stuff and more. But here is a summary.

Two years of COVID-19 in the MS community: What have we learnt so far? Zabalza A, Thompson AJ, Montalban X.Mult Scler. 2022 :13524585221099844. doi: 10.1177/13524585221099844.

Two years have elapsed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic.

At the beginning of the pandemic, research focused on defining the risk of MS patients, untreated and treated, of being infected with COVID-19 or of having a more severe course.

With the introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the centre of attention turned to the immunological response to both SARS-CoV-2 infection and vaccines and the way in which disease-modifying treatments (DMTs) affected these responses.

In addition, the publication of many case reports about demyelinating diseases starting short after COVID-19 or SARS-CoV-2 vaccine raised the question of whether this immune response may trigger MS or other central nervous system autoimmune diseases.

  • Higher disability or a progressive form seem to increase the risk of a severe COVID-19 in pwMS. 
  • Anti-CD20 therapies were the only DMTs that increased the severity risk in some studies.

In view of these facts, some MS centres tried to modify their DMT prescription strategies

  • Some favoured other high-efficacy treatments such as natalizumab instead of anti-CD20 therapies
  • Others successfully implemented extended-interval dosing of anti-CD20 therapies.
  • SARS-CoV-2 vaccine willingness is increased in pwMS compared with the general population

Overall, most pwMS present an immunological response after SARS-CoV-2 infection (humoral response: 76.8%–83.4%; cellular response: 59.5%) or vaccination (humoral response: 74.4%–86.8%; cellular response: 62%–84.4%) regardless of their treatment.

However, it is clear by now that anti-CD20 therapies and sphingosine-1-phosphate receptor modulator (SP1RM) therapies decrease these responses.

SP1RM therapies prevent lymphocytes from leaving the lymph nodes. These treatments present an underwhelming vaccination response in relation to both humoral and cellular responses (11.0%–14.0%).

However, immune responses after infection seem to be relatively preserved (66.7–80.0). Thus, it is possible that the complexity of the immunological responses after natural infection allows the development of an effective response to the virus and a humoral response even in the presence of SP1RM treatment, while post-vaccine immunological responses are much narrower and weaker, blocking the creation of immunological memory.

Probably the most relevant question is whether vaccination prevents severe COVID-19 even in those with blunted vaccine response….A recent pre-print publication detected 137 breakthrough infections out of 19,641 vaccinated pwMS, with significantly higher infection rates in fingolimod- and ocrelizumab-treated patients. In this case, the hospitalization rate was higher in ocrelizumab patients compared with fingolimod or the rest of pwMS (16.7%, 3.6% and 3.9% respectively).

SARS-CoV-2 vaccines have demonstrated to be safe in pwMS however, some rare cases of neurological adverse events, including new diagnoses of MS, transverse myelitis, acute disseminated encephalomyelitis (ADEM) or MS relapses, are being described after all types of SARS-CoV-2 vaccines. At the current state of knowledge, SARS-CoV-2 vaccination is recommended as COVID-19 risk outweighs the risk of rare vaccine adverse events.

I think it has become a game of diminishing returns to look at the daily COVID literature to try and give you an early heads-up of what may happen, but I have a talk to do on this next month so after that it is probably time to say good bye to COVID until something interesting appears as you don’t need to know for the hundredth time that some past work is repeated…That is unless it is our work:-). We know vaccine dose 1-4 is rather rubbish at making antibody response in people treated with anti-CD20 and that BA.3/BA.4 is more likely to escape the vaccination immune response, so it may not be if ,but when you get COVID-19 for the first or repeated time. Hopefully the virus won’t mutate into a more lethal variant.

This report belows suggests additional benefit from boosters

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian Multiple Sclerosis patients, a follow-up studyIdda, ML et al. . MedRXiv .10.1101/2022.05.19.22275317 

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs)……Humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients...but there was an increase …one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. And although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.

Schwarz T, Otto C, Jones TC, Pache F, Schindler P, Niederschweiberer M, Schmidt FA, Drosten C, Corman VM, Ruprecht K. Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis. Mult Scler. 2022 Jun;28(7):1041-1050. doi: 10.1177/13524585221094478.

Yep you guessed it there is a T cell but poor antibody response. after two vaccine doses………………ZZZZZZZZZZZZZZZZZZzzzzzzzzzzzzz

Tolf A, Wiberg A, Müller M, Nazir FH, Pavlovic I, Laurén I, Mangsbo S, Burman J. Factors Associated With Serological Response to SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Treated With Rituximab. JAMA Netw Open. 2022;5(5):e2211497.

Objective: To identify factors associated with a favorable vaccine response to tozinameran.

Exposures: Sex, age, number of previous rituximab infusions, accumulated dose of rituximab, previous COVID-19 infection, time since last rituximab treatment, CD19+ B-cell count before vaccination, CD4+ T-cell count, and CD8+ T-cell count were considered potential factors associated with the main outcome.

Results: Vaccine responses were determined before vaccination with tozinameran (Pfizer) and 6 weeks after vaccination. The proportion of patients with a positive response increased with the number of B cells, which was the only factor associated with these outcomes. A cutoff for the B-cell count of at least 40/μL was associated with an optimal serological response. At this cutoff, 26 of 29 patients (90%) had positive test results for anti-spike IgG and 21 of 29 patients (72%) for anti-RBD IgG, and 27 of 29 patients (93%) developed antibodies with greater than 90% inhibition of angiotensin-converting enzyme 2. No factor associated with the cellular response was identified. Depending on the peptide pool, 21 of 25 patients (84%) to 22 of 25 patients (88%) developed a T-cell response with interferon gamma production at the B-cell count cutoff of at least 40/μL.

Conclusions and relevance: This cohort study found that for an optimal vaccine response from tozinameran, rituximab-treated patients with multiple sclerosis may be vaccinated as soon as possible, with rituximab treatment delayed until B-cell counts have reached at least 40/μL. An additional vaccination with tozinameran should be considered at that point.

Yep you guessed it there B cell numbers are important in antobody responses………………ZZZZZZZZZZZZZZZZZZzzzzzzzzzzzzz

So don’t forget this

Baker D, MacDougall A, Kang AS, Schmierer K, Giovannoni G, Dobson R. CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis. Mult Scler Relat Disord. 2022 Jan;57:103448

No wonder there is a poor response with anti-CD20

And finally….

Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals? Baker D, MacDougall A, Kang AS, Schmierer K, Giovannoni G, Dobson R. Clin Exp Immunol. 2022;207(3):263-271. doi: 10.1093/cei/uxab015.

I think we could have optimized the chance of a protective response but without company guidance, many people (Neuros) are not going to go outside the label and now with anti-virals and less lethal variants, the moment has gone…..so we have to give thanks to preprint publishing because if we have to wait for this info to surface it is too late.

Disclaimer These are the views of the authors

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MouseDoctor

25 comments

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  • Sorry we’ve moved on to Monkey Pox.

    You are behind the times. Did you know that Leeds Utd stayed up?

  • In those people with high disability and progressive MS will having 4 Vaccines ie 2 vaccines and 2 boosters be enough to prevent severe disease?

    I know these people are eligible for antivirals but there are many stories about antivirals not being available and if you are unable to get antivirals because you are away on holiday for example should your covid be manageable with the 4 Vaccines?

  • “The findings suggest [Covid] viral components can contribute to central nervous system immune responses without direct viral invasion” “…the effects we see in biomarker studies are likely a consequence of a general response to the infection throughout the body.” Sooo….relevance to EBV and MS then? I mean, finding EBV in lesions/CSF is elusive, no?

    https://www.medpagetoday.com/neurology/generalneurology/98897?xid=nl_mpt_DHE_2022-05-24&eun=g1536794d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Evening%202022-05-24&utm_term=NL_Daily_DHE_dual-gmail-definition

    • Thanks for this

      Median CSF concentrations of neurofilament light (NfL), a marker of axonal injury, were higher in COVID patients compared with controls (960 vs 618 ng/L, P=0.002), after adjusting for age

  • There is one thing you said I don’t fully understand: are you saying getting a booster after infection is the most successful at preventing disease or are you saying getting COVID will protect you more than any shot will?
    Have just had COVID after one booster and Evusheld and it was not mild by any definition. Trying to figure out if my risk level is now the same as before or better than before with some protection -so would love if you could clarify!
    Could be misunderstanding entirely!

    • Obviously getting COVID will provide better protection as the range of antigens your immune system will be exposed to is far greater than just the spike protein. In addition, remember that all the vacccines are still based on the original Wuhan strain, COVID has mutated extensively since then. In fact, I am greatly surprised the vaccines don’t appear to have been updated to reflect this in the same way flu vaccines are. It’s not as if the likes of (the egregiously profiteering) Pfizer can’t afford to do this.

    • The vaccine gives you a response to Spike (Wuhan) a natural infection gives you protection to Spike, Nucleocapsid, Envelope, Membrane and the other 26 viral proteins and whilst antibodies against receptor binding domain limits infection but remember T cells and they recognise nucleocapsid well.

      • This is a fabulous explanation, thank you.

        In terms of real world implications for pwMS is it then correct to conclude that IN THEORY this would mean that should someone get reinfected after original infection it would be less severe?

        • You would hope so with the caveat that we don’t know how much the virus will mutate in the future, it’s made mugs of many in the prediction business before but so far, nothing too untoward seems to have emerged recently so fingers crossed!

  • My wife was with her consultant yesterday and they are both at a loss for what’s going on and what has happened. Here is a bit of background, she is heavily immunosuppressed(B-Cell depleted with rituxamab and also takes mycophenolate, Azathioprine and prednisone on top of that which reduce T-Cell concentrations) she struggles to even walk up the stairs without pain after 6 steps, but her condition is controlled.

    And then came the Covid infection and Paxlovid(not sure which caused it) the day after the Covid infection she got paxlovid and 2 days after that she said to me “I feel like I have been given 1g of steroids, I honestly feel like I could run a marathon” yes she tested positive again after the Paxlovid finished and the cough and congestion came, but she said she still felt amazing considering(it was me panicking more than anything). Ever since (touch wood) she has had energy she’s never had for decades, no longer in pain going up and down stairs( her muscles are still weak and probably won’t get any better) but this is unbelievable, yesterday with her consultant her CK levels were almost in the normal range, a level that she hasn’t had for almost 23 years.

    We’re still very weary of Covid because we know the next time could be very different, I just though I would share whats happened to her.

      • No, all she was given was the paxlovid(she said she felt like she had been given a gram of steroid, she had that much energy), so also had a Covid/Paxlovid rebound and tested positive again 2 days after the Paxlovid finished.

    • Most interesting.

      I wonder if we will find that one of the antivirals in paxlovid is anti EBV? Isn’t ritonavir originally a HIV HAART some of which are already thought to work against EBV?

      • You could be onto something there TBH, as it’s certainly had an effect on my wife, hopefully it lasts.

      • If only the ProfGs had tested HAART, as hoped, rather than raltegravir you may have had more insight

        • I am still wondering if I should try to get on some variation of PrEP… Considering people use it as a lifestyle medication (more or less) , I presume side effects can’t be too horrible.

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