MS COVID19 Sunday lunch.

M

During COVID the standard publication process has been thrown out of the windown. Whereas it may take 6-12 months for a standard paper to arrive, with preprint sites, stuff arrives online within 2-3days. In the COVID era these views are either supported or refuted 9-10 times in a few moments more. So sadly by the time the experts have got together to make a consensus, life has moved on and the experts are so far behind the curve….Do we believe the experts?

I once met Prof Coyle doing a debate with ProfK or is that Prof.Santaclaus….and I would’nt want to meet her in and Ally on a dark night….Only Joking. Im sure the Barks is more scary than the bite:-

Coyle PK, Gocke A, Vignos M, Newsome SD. Vaccine Considerations for Multiple Sclerosis in the COVID-19 Era. Adv Ther. 2021 Jun 1:1–39. doi: 10.1007/s12325-021-01761-3.

People with multiple sclerosis (MS) are at risk for infections that can result in amplification of baseline symptoms and possibly trigger clinical relapses. Vaccination can prevent infection through the activation of humoral and cellular immune responses (NSS). This is particularly pertinent in the era of emerging novel vaccines against severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019 (COVID-19). MS disease-modifying therapies (DMTs), which affect the immune system, may impact immune responses to COVID-19 vaccines in people with MS. The objective of this article is to provide information on immune system responses to vaccinations and review previous studies of vaccine responses in people with MS to support the safety and importance of receiving currently available and emerging COVID-19 vaccines. Immunological studies have shown that coordinated interactions between T and B lymphocytes of the adaptive immune system are key to successful generation of immunological memory and production of neutralizing antibodies following recognition of vaccine antigens by innate immune cells. CD4+ T cells are essential to facilitate CD8+ T cell and B cell activation, while B cells drive and sustain T cell memory. Data suggest that some classes of DMT, including type 1 interferons and glatiramer acetate, may not significantly impair the response to vaccination. DMTs-such as sphingosine-1-phosphate receptor modulators, which sequester lymphocytes from circulation; alemtuzumab; and anti-CD20 therapies, which rely on depleting populations of immune cells-have been shown to attenuate responses to conventional vaccines. Currently, three COVID-19 vaccines have been granted emergency use authorization in the USA on the basis of promising interim findings of ongoing trials. Because analyses of these vaccines in people with MS are not available (yes they are in part), decisions regarding COVID-19 vaccination and DMT choice should be informed by data and expert consensus, and personalized with considerations for disease burden, risk of infection, and other factors.

So our predictions came to fruition

Negative SARS-CoV2-antibodies after positive COVID19-PCR nasopharyngeal swab in patients treated with anti-CD20 therapies.Friedli C, Diem L, Hammer H, Kamber N, Suter-Riniker F, Leib S, Chan A, Hirzel C, Hoepner R, Salmen A.Ther Adv Neurol Disord. 2021 May 18;14:17562864211016641.

Therefore, the finding of a lacking antibody response after a symptomatic COVID-19 in patients treated with anti-CD20-therapies may imply an increased risk for re-infection. In addition, anti-CD20-therapies may lead to an absent antibody response to SARS-CoV2-vaccines, as has been predicted by Baker et al. (Yep you heard it here forst folks) In our opinion, this should prompt closer surveillance including monitoring of the immune response in patients treated with anti-CD20-therapies after both infection and vaccination, in order to clarify whether these individuals remain at risk for SARS-CoV-2 infection. If vaccination or infection fails to protect a high proportion of patients on anti-CD20 therapy, the safekeeping of these vulnerable individuals will depend on herd immunity and individual protective measures such as physical distancing and following hygiene rules.

We have suggested that we all may be offered a third vaccine. This has already been done and it improves the serconversion rates in some people with cancer getting the third vaccine. However, I will say they have answered the question because the people with cancer that do not respond well to and the people with blood cancers and not solid tissue cancers

Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series, William A. Werbel, MDBrian J. Boyarsky, MD, PhDMichael T. Ou, BS… View all authors Author, Article and Disclosure Informationhttps://doi.org/10.7326/L21-0282

It is encouraging that antibody titers increased after the third dose in one third of patients who had negative antibody titers and in all patients who had low-positive antibody titers.

In the study above the third dose seemed to be an adenoviral (J&J) after a RNA vaccine start. It seems there is one advantage of the AZ vaccine…It allows Canadians the opportunity to not go to a Bruce Springteen concert in New York…….Only Joking…before the Boss fans start to Revolt. However if you ask which Vaccine induced the highest levels of antibodies, I would say the RNA vaccines are the best and notably the Moderna vaccine (orange below) and give a higher level than Pfizer (blue below)

Iles et al Differences in IgG antibody responses following BNT162b2 and mRNA-1273 Vaccines. MedRxiv https://doi.org/10.1101/2021.06.17.21259077

This isn’t surprsing as you get 3 times more RNA with Moderna (RNA 1273)

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MouseDoctor

8 comments

  • A question about anti CD20 MD. If these patients are relying on their t-cell response and subsequently go on to Alemtuzumab – are they making themselves sitting ducks in that tcells will be depleted as well

      • Sorry, not sure I understand the response. A patient gets 2 jabs in between ocreluzumab infusions so antibody response is likely to be non existing. Said patient may generate a t-cell response. However, subsequently shifts to t-cell depleter (alem) – are they more at risk than before alem or just the same?

        • The study’s major findings, include:

          Antiviral T cells that reside in most organs of the body persist over time and in the face of extensive infectious exposures;
          Unlike other organ systems, the immune system becomes increasingly immune throughout life, which is a natural response to accumulated microbial exposures over time;
          Up to 25% of the cells in organs were immune cells, indicating that the immune system significantly contributes to the cellular makeup of the body;
          And, along with antiviral T cells, most other immune cells are durably tissue-resident in organs as well.

          New findings suggest organ tissues become increasingly immune throughout life

          https://medicalxpress.com/news/2021-04-tissues-increasingly-immune-life.html

  • Yes encouraging that a third dose might be of huge assist to those of us on B cell depleting DMTs (Ocrevus here). Question: any thoughts on timing for that third round?

    • From what I understand, and this could be wrong, so please consult your HCP, the *assumption* is to wait (length of time varies on average many months to 3+ years per MD) for your B cells to repopulate to a certain level (of which amount is unclear to me) that would be useful for vaccination. Upon reaching these thresholds, one can presumably revaccinate, perhaps with Moderna since it promotes the highest antibody response I think. The question I have is what does one use to control MS disease in the interim provided one chooses to walk away from anti CD20 meds? I have heard Tysabri is an option as it does not largely impair covid vaccination efficacy but would appreciate thoughts on that proposition. Moreover, I still would like more discussion as to why the notion of antibody cocktail is not gaining more traction as a method to protect so many immune compromised people with poor (if any) vaccine response.

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