#MSCOVID19 MDs Saturday COVID Lunch

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Politicians need to do more for Vaccine Confidence….when they open their mouth, some times they need to put a sock in it.

This study was done in January nearly 80% in UK would vaccinate but in France it is 40% and Germany Spain and Italy about 50%…I bet when the next survey is done we may see a dip and this has not been helped by stupidity by some politicians who are not doing their bit to promote vaccine confidence, and seem to be more interested in vaccine nationalism and point scoring.

International attitudes on COVID-19 vaccination: repeat national cross-sectional surveys across 15 countries Roberto Fernandez Crespo, Manar Shafat, Natalie Melas-Kyriazi, Lisa J Gould, Sarah Jones, Ana Luisa Neves, Melanie S Leis, Hendramoorthy Maheswaran, Ara Darzidoi: MedRXiv https://doi.org/10.1101/2021.03.08.21252449

Objective: To examine the general publics views around willingness to receive COVID-19 vaccines and concerns regarding their safety. Design: Repeat cross-sectional surveys. Setting: Online surveys in Australia, Canada, Denmark, Finland, France, Germany, Italy, Japan, Netherlands, Norway, Singapore, South Korea, Spain, Sweden and the United Kingdom Participants: National samples of adults aged 18 years and above in November 2020 and January 2021. Main outcomes measures: The proportion of adults reporting: willingness to receive a COVID-19 vaccination; concern regarding side-effects from vaccinations; concerns over contraction COVID-19, and beliefs around vaccine provision in their country. Changes between the November and January surveys are also reported. Results: Across the 15 countries, the proportion of respondents reporting they would have the COVID-19 vaccine increased from 40.7% (range: 25.0-55.1) to 55.2% (range: 34.8-77.5), proportion reporting worried about the side-effects of vaccine decreased from 53.3% (range: 42.1-66.7) to 47.9% (range: 28.0-66.1). On the second survey, willingness to receive vaccine remained low in females (49.4%, range: 30.2-79.1), aged 18-39 years (42.1%, range: 25.9-71.7), those not working or unemployed (48.9, range: 18.8-67.0), students (45.9%, range: 22.8-70.0), and those with children at home (46.5%, range: 32.4-68.9). Concerns regarding safety of vaccine remained high in females (53.7%, range: 31.8-70.4), aged 18-39 years (50.8%, range: 28.2-60.7), aged 40-64 years (51.3%, range: 30.7-68.5), those working (50.5%, range: 26.7-65.0), those not working or unemployed (53.3, range: 35.4-73.8) and those with children at home (55.8%, range: 36.5-64.7). Conclusion: COVID-19 vaccine hesitancy decreased considerably over a relatively short time coinciding with the discovery of effective vaccines. The public remain concerned about their safety, and public health messaging will need to emphasis their safety especially amongst females, parents and younger adults.

Anti-CD20 (rituximab) use is associated with an increased hospitalization risk

Multiple sclerosis, rituximab, and COVID-19.Langer-Gould A, Smith JB, Li BH; KPSC MS Specialist Group.Ann Clin Transl Neurol. 2021 Mar 30. doi: 10.1002/acn3.51342. We conducted a retrospective cohort study in Kaiser Permanente Southern California from 1 January 2020 to 30 September 2020. We found that rituximab-treated persons with multiple sclerosis (pwMS, n = 1895) were more likely be hospitalized (n = 8, 33.3%), but not die (n = 0) from COVID-19, compared to the 4.81 million non-MS population (5.8% and 1.4%, respectively). Time in months (adjusted OR = 0.32, 95% CI = 0.15-0.69, p = 0.0033) and receiving 1000 mg compared to lower doses at last infusion (adjusted OR = 6.28, 95% CI = 1.38-28.5, p = 0.0173) were independent predictors of COVID-19 severity. Rituximab-treated pwMS should be counseled to take extra precautions in the 5 months following each infusion. Using extended dosing intervals and lower doses could be considered.

So another study implicating CD20 treatment as a risk of hospitalisation. Therefore, studies with rituximab question that reported with ocrelizumab that duration of treatment contributes to risk of COVID-19. Will it be repeated .click your fingers and the answer is yes. See below Higher doses were associated with increase risks also. They make suggestions for longer dosing intervals. I suspect many places will be auditing their service to determine whether ther was any impact of delaying dosing. Im sure the answer will be, it is feasile. We need more trials to document that this can be done safely.

orange indicates when COVID-19 developed

I keep repeating myself. I say again anti-CD20 (rituximab) use is associated with an increased hospitalization risk

The most damming data on the COVID-19 risks associated with rituximab use comes from Rituxiland or Sweden as some of you know it. They use large amounts of rituximab and did not lock down. thereofre they have a large data set. When first presented in June 2020 it looked like there was an potential increase risk of covid-19 infection. But this is difficult to show but yet more data that use of rituximab is associated with an increase risk of hosptilization. Maybe I don’t need to labour this point anymore. The data indicates the risks with ocrelizumab is lower, but biologically this does not make sense and is probably just part of variation. It also further suggests that long term- CD20 depletion is an infection ticking time bomb. The community needs to look in to reduced interval dosing. The COVID-19 pandemic has served to wake people up to this.

Increased rate of hospitalisation for COVID-19 amongst rituximab treated multiple sclerosis
patients: a study of the Swedish MS registry. Spelman T, Forsberg L, McKay K, Glaser A, Hillert J. SSRN 2021; DOI: 10.2139/ssrn.3801769 

Background: The primary objective of this study was to analyse the association between multiple sclerosis (MS) disease modifying therapy (DMT) exposure and subsequent hospitalisation in patients infected with COVID-19.

Methods: Data were extracted on the 18th January 2021 from the Swedish MS Registry, which collates nationwide, prospectively-collected clinical, demographic and, from March 2020 onwards, Covid-19-related information; (including diagnostics and need of health care including needs of hospitalization, intensive care and ventilation) among persons with MS. Associations between MS DMT exposure and COVID-19 hospitalisation were analysed using univariable and multivariable clustered logistic regression, where the models were clustered on the individual patients to control for patients contributing multiple COVID-19 episodes. Propensity score based inverse probability of treatment weighting (IPTW) approach was used to adjust for confounders. Findings: As of 18th January 2021, a total of 476 reported COVID-19 cases had been recorded in MS patients in the Swedish MS registry. Of these, 292 (61.3%) had confirmed COVID-19. The mean (SD) age at infection was 44.0 years (11.6). Of the 292 confirmed infections 68 (23.2%) required hospitalisation. A total of 49 of the 164 confirmed COVID-19 patients on rituximab at baseline (29.9%) required hospitalisation, compared to a rate of 12.7% for all other DMTs combined. Rituximab in confirmed COVID-19 patients was associated with 2.95 times the weighted odds of hospitalisation relative to treatment with any other alternate DMT combined (Odds Ratio 2.95; 95% CI 1.48-5.87). The risk of severe COVID-19 increased with duration of rituximab treatment with a yearly Odds Ratio of 1.24 (95% CI 1.04-1.48).

Interpretation: Rituximab treatment, known to increase the risk of severe infections in general, also confers such a risk for MS patients with COVID-19, in comparison with other MS DMTs.

You need your seccond dose to optimally protect yourself.

Kennedy et al. medRxiv preprint doi: https://doi.org/10.1101/2021.03.25.21254335

This study is not based on data in MS, but this will be coming soon. Infliximab is a potent anti arthritis drugs and its used is associated with a blunted vaccine response. TNF is a survival factor for some subsets of B cells and its inhibition is associated with loss of B cell follicles for where antibody forming plasma cells are generated. Vedolizumab is a migration inhibition drug abit like natalizumab (anti-alpha 4, beta 1)

We need to see the effect of the Oxford/Astrazeneca vaccine

This the same in cancer treatment too

It also says lack of seroconversion is associated with B cell depletion, which is not good news fo ocrelizumab users and is also says that T cells can be generated in B cell depleted individuals. However, from a glass half-empty perspective 50% of people did not develop a T cell response. This is probably going to happen with vaccination of MSers with COVID-19 vaccines.

T cells are important in getting rid of COVID-19 virus

Chandran et al. Non-severe SARS-CoV-2 infection is characterised by very early T cell proliferation independent of type
1 interferon responses and distinct from other acute respiratory viruses. medRxiv preprint doi: https://doi.org/10.1101/2021.03.30.21254540

The correlates of natural protective immunity to SARS-CoV-2 in the majority who experience
asymptomatic infection or non-severe disease are not fully characterised, and remain important as new
variants emerge. We addressed this question using blood transcriptomics, multiparameter flow
cytometry and T cell receptor (TCR) sequencing spanning the time of incident infection. We identified a
type 1 interferon (IFN) response common to other acute respiratory viruses, and a cell proliferation
response that discriminated SARS-CoV-2 from other viruses. These responses peaked by the time the
virus was first detected, and in some preceded virus detection. Cell proliferation was most evident in
CD8 T cells and associated with rapid expansion of SARS-CoV-2 reactive TCRs. We found an equally
rapid increase in immunoglobulin transcripts, but circulating virus-specific antibodies lagged by 1-2
weeks. Our data support a protective role for rapid induction of type 1 IFN and CD8 T cell responses to
SARS-CoV-2.

T cell response
B cell response

Dried Blood Spots Work

BNT162b2 Vaccination in People Over 80 Years of Age Induces Strong Humoral Immune Responses with Cross Neutralisation of P.1 Brazilian Variant. SSRN 2021: https://ssrn.com/abstract=3816840

In this study in old people it shows that the blood spot technology works. They examined people that had COVID-19 (blue) and compared this to vaccinated people (red) [Top left]. If you have hospitalised people they make high levels of antibody. You can distinguish infected from vaccinated people. [Top right], as the infected people have both a Spike and nucleocapsid response, but if you are vaccinated you only make Spike antibodies (cut off for positive = 1 = 1 x 10*0. Importantly the dried blood spot (DBS) levels correlate with the blood levels [bottom left] and that antibodies against Spike increase between the first and the second dose of the Pfizer vaccine [Bottom right].

With Dr Angry’s GloBodies tests we can do the same only we dont have to pay hundreds of Squids to do this and the test is properly quantiative as the test used in the study above will miss two thirds of the IgG antibody. Why because the test uses one arm of the anti-body to bind to the detect reagent whilst the other binds to the capture agent, but means you can get both arms bind to capture and so are not detected or both bind detect and so are not captured. Also for one molecule of IgA (it has 4 antibody arms) one molecule can give one detect signal (the other arms are filled with 3 captures) or 2 or 3 detects (the other arms are filled with a capture). There should be too much IgM but one molecule can give from one to 9 detection signals has it has 10 arms. Importantly the test above detects antibodies to all of Spike, but Dr Angry has made a reagent to the receptor Binding domain which is the bit of Spike used for infection.

Blood clotting

Blood clotting is in my opinion the central problem in COVID-19, fill your blood vessels up withblood clots and it is hard to breathe, but blood clots in your brain and it is hard to think and may cause stroke. There has been some concern about COVID-19 vaccine-associated blood clotting, which is very rare, and this is recognised and risk mitigation processes have been put in place…let’s call it the flight sock vaccine approach. Why? Well you know that flying can be associated with blood clotting if you sit too long, so you wear elastic stockings/socks to assist in blood flow. Here it is

The UK is not Herding yet (info source. Office National statistics)

To get herd imunity n

In England, an estimated 1 in 2 people, or 54.7% of the population (95% credible interval: 49.3% to 60.5%)
would have tested positive for antibodies against the coronavirus – SARS-CoV-2 – on a blood test in the
week ending 14 March 2021, suggesting they had the infection in the past or have been vaccinated.

In Wales, an estimated 1 in 2 people, or 50.5% of the population (95% credible interval: 44.2% to 57.2%)
would have tested positive for antibodies against SARS-CoV-2 on a blood test in the week ending 14
March 2021, suggesting they had the infection in the past or have been vaccinated.

In Northern Ireland, an estimated 1 in 2 people, or 49.3% of the population (95% credible interval: 41.8% to
59.7%) would have tested positive for antibodies against SARS-CoV-2 on a blood test in the week ending
14 March 2021, suggesting they had the infection in the past or have been vaccinated.

In Scotland, an estimated 2 in 5 people, or 42.6% of the population (95% credible interval: 37.1% to 48.6%)
would have tested positive for antibodies against SARS-CoV-2 on a blood test in the week ending 14
March 2021, suggesting they had the infection in the past or have been vaccinated.

In England in the week ending 14 March 2021, the percentage of people testing positive for antibodies:
for those aged 80 years and over was 86.0% (95% credible interval: 79.0% to 90.5%)
aged 75 to 79 years was 88.5% (95% credible interval: 83.9% to 92.1%)
aged 70 to 74 years was 91.3% (95% credible interval: 87.6% to 94.0%)
aged 65 to 69 years was 89.0% (95% credible interval: 84.8% to 92.5%)
The percentage of people testing positive for antibodies in those aged 16 to 64 years ranged from 40.9% to
57.6%

About the author

MouseDoctor

6 comments

  • You say politicians need to do their bit for vaccine confidence, but several Barts-ers have shared links to articles about the new MRHA blood clot deaths data this weekend, with no reassurance or commentary. As a young woman, I previously had no vaccine hesitancy but am beginning to think my personal risk from COVID-19 is lower than my risk from the vaccine, and yet all the reporting shares only figures from the population as a whole, not the group seemingly at increased risk of these rare clotting disorders.

  • Every time I come here I get the overwhelming feeling that I’m on the duff treatment, the one that brings with it all the risk. I know people say risk of MS is worse than covid, but what about those of us whose profession exposes us to covid more? I have some difficult decisions to make I think…

    Also, why is it that IBD and arthritis and other auto immune guys, plus cancer people have plenty of data on vaccine out but nothing yet for MS?

    • Every treatment and every compound has risks. If I pick up a pot of glucose, thats sugar to you and me, we should be wearing respirator masks….however they have all be taken by the COVID mayhem.

      Nothing for MS. That is not true, we have already provided data for anti-CD20, fingolimod and cladribine. The latter was a unknown and the former were predicted to have blunting. However that data has only been presented and not published.

      However to address yourself, arthritis is over twenty times more common than MS and as for Cancer over 200 times more, so the studies are easier and have been funded by central government. Then you ask how did the IBD patients get vaccinated do early, but fear not MS will surface in the next month I suspect. In the UK the question is what is the issue with the long interval dosing schedule.

  • When it comes to boosters of the vaccine, and vaccination into the future, will this start to be done in GP surgeries?

    • I don’t know, I believe Moderna started testing of their new variant last week..they have to shown to be of value

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