#MSCOVID19 when the theorectical becomes a reality…CD20 and vaccine readiness

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ProfG caused a stir when he suggested that people taking anti-CD20 may be at a small increased risk of developing COVID-19. However, would we expect this?. If it makes a small increased risk of other infections. why not this one?

However, the other reality that we could predict ,was that if you have no B cells it is going to be more difficult to make antibody responses to SARS-CoV-2.

In this case report 7 people get infected, 3 get hospitalised some made an antibody response, but others did not despite being tested positive with the viral DNA . So will CD20 depletion inhibit capacity to make a a full vaccine response? I suspect the answer is yes. It’s biology 101.

COVID-19 IN 7 MULTIPLE SCLEROSIS PATIENTS IN TREATMENT WITH ANTI-CD20 THERAPIES Dra. Virginia Meca-Lallana, Dra. Clara Aguirre, Beatrizdel Río, Dra. Laura Cardeñoso, … Dr. José Vivancos Mult Scler Rel Disord In Press, Journal Pre-proof, Available online 15 June 2020.

Now one of the people was asyptomatic and did not make an antibody response but even people who don’t have DMT treatment do not make an antibody response. But there was one person who was symptonmatic but didn’t make an antibody response. There are others

So the question is….Is the antibody response enough to give protection against SARS-CoV-2?

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MouseDoctor

18 comments

  • My favourite thing about this is that it is possible to have mild or even asymptomatic COVID-19 whilst on anti CD20. Very encouraging!
    Also it adds to the general thought that age etc is a predictor for worse disease.

    Theoretically do we know how long we should leave between an infusion and a vaccine to have the most hope of a response?

    And am I going to be the first to ask – which DMT shall we move to if we decide anti CD20 isn’t for us in the current climate?

    • 50% of people have asymptomatic COVID-19.
      How long…..See my paper out this week…
      If I was switching….I’m not allowed to say

  • “Test positive for viral DNA”…..Its a positive sense strand RNA virus. Yeah, the test is a RT-PCR so the amplified product would be DNA. Just nitpicking:-)

      • I thought that Polymerase Chain Reactions could made to detect DNA or RNA and in the case of CoVID-19 it was an RNA virus? In my naïvety I had always thought that this was really a NAAT like we use to detect Chlamydia. The question that really interests me is given that the half life of ocrelizumab is 672 hours, how long after an infusion will levels fall to a level sufficiently low to permit vaccines to work. Obviously, every individual will be different and there will probably be a normal distribution around around a point estimate, so you probably want to use the upper limit of the 95% CI range so that most people (97.5%) will benefit from the vaccine.

        • It can, but the PCR amplifies DNA, and you are right COVID is an RNA virus and you reveerse transcribe the RNA to DNA and then amplify it.

          How long. Good question The clinical dose is 600mg and a 20mg dose depletes peripeheral blood B cells so there is about 5 half lives. My guess is as long as you are continually taking ocrelizumab you will never be in an optimum space for vaccine. However we dont know what we are aiming to achieve and it may be a low bar or a high bar. Rituximab studies indicate it will e sometime. If you stop and wait for the B cells to come back, after 3 cycles the median time taken to get to get CD19 to lower limit of normal is about 62 weeks after 4 cycles it is 72 weeks (range 27-175 weeks). As soon as the paper is on pre-print server, I will address this further should be soon

  • Given that Ocrelizumab has lowered my IgM, does this mean that the lateral flow immunoassay’s results would be unreliable as a marker of previous exposure and isn’t IgM more important in the acute response than IgG anyway?

    • In terms of assay, if it is negative there is a chance you have had the virus. It depends when you think you were infected to help determine the chance of IgM still being present. You are probably right that IgM and IgA responses are more important than IgG. But for neutralization against re-infection I am guessing IgG would be more relevant

      • I’m confident I have not had the virus because the small team I work with all tested negative and only 2 people with CoVID symptoms visited my workplace saying that they had no flulike symptoms (it later transpired they didn’t realise that fever, cough, shortness of breath, sore throat and myalgia were ‘flulike‘ symptoms – all of which they had). The background seroconversion rate is 4% locally and we’re down to <5:100,000 active infections. I suspect the slightly worse outcomes for pwMS, treated with Ocrelizumab, that Gavin highlights are due to failure to mount an adequate IgM response.

        • You could be correct delayed IgM and IgA responses are associated with worse outcome, this all in the new paper

          • “COVID-19 vaccine-readiness for ocrelizumab and other anti-CD20-depleting therapies in multiple sclerosis and other autoimmune diseases”
            The preprint will be visible very soon

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