If you have MS and live in the UK read this

Here are options if you get infected, but you have to get tested (PCR) and act within 5 days of symptom onset…Don’t be the person who spends Christmas and New Year in Hosptial

Humoral and cellular immune responses to SARS CoV-2 vaccination in Persons with Multiple Sclerosis and NMOSD patients receiving immunomodulatory treatments Bock, H., Juretzek, T., Handreka, R., Ruhnau, J., Reuner, K., Peltroche, H., Dressel, A. MedRXiv 10.1101/2021.12.22.21268127 Background: Vaccination against SARS CoV-2 results in excellent personal protection against a severe course of COVID19. In persons with Multiple Sclerosis (PwMS) vaccination efficacy may be reduced by immunomodulatory medications.

Objective: To assess the vaccination induced cellular and humoral immune response in PwMS receiving disease modifiying therapies.

Methods: In a monocentric observational study on PwMS and patients with Neuromyelitis optica we quantified the cellular and humoral immune responses to SARS CoV-2.

Results: PwMS receiving Glatiramer acetate, Interferon-beta, Dimethylfumarate, Cladribine or Natalalizumab had intact humoral and cellular immune responses following vaccination against SARS CoV-2. B-cell depleting therapies reduced B-cell responses but did not affect T cell responses. S1P inhibitors strongly reduced humoral and cellular immune responses. There was a good agreement between the Interferon gamma release assay and the T-SPOT assay used to measure viral antigen induced T-cell responses.

Antibody response is inhibited by use of anti-CD20 depleters and sphingosine-1-phophosphate modulators
T cell response is inhibited by use of sphingosine-1-phophosphate modulators

Conclusion: This study demonstrates that S1P inhibitors impair the cellular and humoral immune response in SARS CoV-2 vaccination, whereas patients receiving B-cell depleting therapies mount an intact cellular immune response. These data can support clinicians in counselling their PwMS and NMOSD patients during the COVID 19 pandemic.

The CD20 pwMS were mainly taking ocrelizumab but rituximab and ofatumumab were in the mix and most S1P1 modulators were fingolimod (4/5 responders), but there were others including ozanimod (n=1) and siponimod (n=1). This says what we have already heard about the impact of MS on vaccine responses, in that S1P modulators and ant-cD20 responses are inhibited but what are the consequences? We know that antibody levels limit infection

Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapiesSormani, M. P., Schiavetti, I., Inglese, M., Carmisciano, L., Laroni, A., Lapucci, C., Visconti, V., Serrati, C., Gandoglia, I., Tassinari, T., Perego, G., Brichetto, G., Gazzola, P., Mannironi, A., Stromillo, M. L., Cordioli, C., Landi, D., Clerico, M., Signoriello, E., Frau, J., Ferro, M. T., Di Sapio, A., Pasquali, L., Ulivelli, M., Marinelli, F., Manzino, M., Callari, G., Iodice, R., Liberatore, G., Caleri, F., Repice, A. M., Cordera, S., Battaglia, M. A., Salvetti, M., Franciotta, D., Uccelli, A. MedRXiv 10.1101/2021.12.23.21268177 

Background. Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to mRNA-based SARS-CoV-2 vaccines, while the degree of such responses is unimpaired and similar in pwMS treated with other disease modifying therapies (DMTs), or untreated. However, the nature of the SARS-CoV-2 vaccine-induced immune response is based also on cellular immunity and there is emerging evidence that anti-SARS-CoV-2 specific CD4 and CD8 T cell responses can be detected after vaccination also in patients with low antibody levels. In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection and to identify correlates of reduced protection in frail vaccinated pwMS on different DMTs.

Methods. We designed a long term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) , a prospective multicenter cohort study enrolling pwMS scheduled for SARS-CoV-2 vaccination with mRNA vaccines and tested for SARS-CoV-2 antibodies before and after the second vaccine dose. These patients were followed with periodic phone calls up to a mean time of 6 months, and all the SARS-CoV-2 breakthrough infections were registered. The impact of DMTs on cumulative incidence of breakthrough Covid-19 cases was presented.

Findings. 1705 pwMS (81.6% BNT162b2 and 18.4% mRNA-1273) had a full vaccination cycle (2 vaccine doses, 21/28 days apart). Of them, 1509 (88.5%) had blood assessment 4 weeks after the second vaccine dose. During follow-up, 23 breakthrough Covid-19 infections (cumulative incidence: 1.5%, SE=0.3%) were detected after a mean of 108 days after the second dose (range, 18-230). Of them, 9 were on ocrelizumab, one on rituximab, 4 on fingolimod, 6 on dimethyl-fumarate, one on teriflunomide, and 2 were untreated. Just two cases (a woman on ocrelizumab and a man on teriflunomide) required hospitalization. The probability to be infected was associated only with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.63, p=0.007); an antibody level of 660 U/mL was calculated as the cut-off for higher risk of infection. Interpretation. Our data show that the risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response.

Disease breakthrough is more common in people with low antibody responses. Therefore people vaccinated with adenoviral vector have a greater infection risk than the RNA vaccies because they induce lower levels. However, with an RNA booster you get a high antibody response. This also indicates the longer you are from your vaccination., the greater the risk of infection as your antibody responses wane with time. So ensure you get your boosters. If you do get infected then you may need an antiviral. We known that many neutralizing antiviral antibodies do not react well with omicron, but most ant-viral chemicals work against the variants of concern.

Vangeel et al. Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. MedRXiv doi:

The in vitro effect of GS-441524 (metabollite of remdesivir), remdesivir (a prodrug of GS-441524), EIDD-1931 (a metabolite of molnupiravir), molnupiravir and nirmatrelvir (one of the anti-virals in paxlovid) against the various SARS-CoV-2 Variants of Concern, including Omicron, was determined. A SARS-CoV-2 strain grown from the first Belgian patient sample was used as ancestral strain. All the other isolates were obtained from patients in Belgium as well. Our results indicate that GS-441524, remdesivir, EIDD-1931, molnupiravir and nirmatrelvir retain their activity against the Alpha, Beta, Gamma, Delta and Omicron. This is in accordance with the observation that the target proteins of these anti-virals are highly conserved.

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