Barts-MS rose-tinted-odometer: ★★★
I have hypothesised that the reason pwMS on anti-CD20 therapy are at greater risk of getting COVID-19 and severe COVID-19 is not about the now, but the past. There is really no reason why a pwMS on anti-CD20 therapy is at increased risk of getting exposed to SARS-CoV-2 compared to pwMS on other DMTs, be it injectables, oral tablets or other infusion therapies. However, people on anti-CD20 therapies are likely to have blunted cross-reactive immune responses to community-acquired coronaviruses. This cross-reactive immunity is protective and reduces your chances of getting symptomatic or severe COVID-19, in other words in the figure below, cross-reactive immunity shifts the population to the left and being on an anti-CD20 therapy prevents this immunity from developing and shifts the curve to the right. I hope this makes sense.
In the study below on healthcare workers, SARS-CoV-2 cross-reactive antibodies elicited by past common community-acquired coronavirus infections were not associated with protection; however, the duration of symptoms following SARS-CoV-2 infections was significantly reduced in individuals with higher antibody titers, i.e. less severe infection.
As antibody titers decline over time after common coronavirus infections, individuals with higher anti-coronavirus antibody titers are more likely to be recently infected with community-acquired common coronaviruses compared to individuals with lower antibody titers. Therefore recent community-acquired coronavirus infections are likely to prevent or reduce the severity of COVID-19 in line with my hypothesis above. What is different is that this protection is unlikely to be purely antibody-mediated, but rather T-cell responses are likely to be responsible for this protection.
What is the relevance of these findings? I suspect that anti-CD20 therapies also blunt protective T-cell responses; possibly by reducing the efficiency of SARS-CoV-2 antigen presentation to T-cells. Based on this study and what happens to people on anti-CD20 who get COVID-19 I would not be surprised if T-cell COVID-19 vaccine responses on anti-CD20 therapies are blunted, similar to antibody responses. The good news is that we won’t have to wait too long for this data to emerge.
Please note, although interesting, this data does not change my current advice, i.e. #StayCalm and #GetVaccinatedASAP.
Gouma et al. Sero-monitoring of health care workers reveals complex relationships between common coronavirus antibodies and SARS-CoV-2 severity. MedRxIV 2021 https://doi.org/10.1101/2021.04.12.21255324
Recent common coronavirus (CCV) infections are associated with reduced COVID-19 severity upon SARS-CoV-2 infection, however the immunological mechanisms involved are unknown. We completed serological assays using samples collected from health care workers to identify antibody types associated with SARS-CoV-2 protection and COVID-19 severity. Rare SARS-CoV-2 cross-reactive antibodies elicited by past CCV infections were not associated with protection; however, the duration of symptoms following SARS-CoV-2 infections was significantly reduced in individuals with higher common betacoronavirus (βCoV) antibody titers. Since antibody titers decline over time after CCV infections, individuals in our cohort with higher βCoV antibody titers were more likely recently infected with common βCoVs compared to individuals with lower antibody titers. Therefore, our data suggest that recent βCoV infections potentially limit the severity of SARS-CoV-2 infections through mechanisms that do not involve cross-reactive antibodies. Our data are consistent with the emerging hypothesis that cellular immune responses elicited by recent common βCoV infections transiently reduce disease severity following SARS-CoV-2 infections.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.
so i thought OCR just influences B-cells but not T-cells and the mRNA vaccines have high t-cell response? what do i miss here? i gonna have an ELISPOT t-cell test next week as the antibody screen was negativ and will let you know what the outcome was.. (6th OCR cycle and vaccine shots 20 and 24 weeks after last dose)
Ocrelizumab hits T-cells numbers by about 15%-20% with a greater impact on CD8+ T-cells. The latter explains why there is a herpes zoster signal with ocrelizumab.
T-cells and B-cells are two sides of the adaptive immune coin. There is a lot of cross-talk between them; for example, B-cells are critically important antigen-presenting cells particularly for recall antigens and possibly onco- or tumour-associated antigens. T-cells are also critical to help B-cell class-switch and affinity mature. Immunology is never all or nothing. Let’s wait to see the T-cell data. If my hypothesis is correct then vaccine immunity, in general, will be poorer on anti-CD20 therapies compared to other DMTs, with the possible exception of the S1P modulators.
Is it therefore the case that lockdowns reduce the number of recent (other) coronavirus infections, and so is likely to result, on an individual level, in more serious Covid 19 infection?
Yes, I suspect you are correct.
If vaccine immunity is poorer on anti CD 20 treatments what do you think will be the solution for those on eg Ocrevus? I would really like to be offered tysabri. NICE guidelines would need altering though as I have no new spots on my scan so I’m stuck on Tecfidera at the moment and have had a relapse recently and tow relapses prior to Ocrevus while I was on Tecfidera (which is why I changed to Ocrevus). I just want a high efficacy drug that allows good vaccine immunity and this is proving so difficult to get right now. All because new spots on a scan are necessary to change. Help!
I’m not quite sure how to interpret this post and the data.
If (hypothetically) the T-cell responses are also blunted, could this mean that vaccination will be ineffective in patients treated with ocrelizumab? Or do you think it would still reduce the chances of severe covid-19? And what about rituximab treated patients?
Re: “T-cell responses are also blunted, could this mean that vaccination will be ineffective in patients treated with ocrelizumab?”
Yes, but this is a grey zone. Less effective in preventing SARS-CoV-2 infection, less effective in preventing SARS-CoV-2 shedding, less effective in preventing COVID-19, less effective in preventing severe COVID-19 and possible death, but more effective than not being vaccinated at all.
Re: “And what about rituximab treated patients?”
This applies to all anti-CD20 therapies, not just ocrelizumab.
so the only hope left for OCR is the “covid pill” – Pfizer’s new at-home pill to treat Covid could be available by end of the year, Pfizer CEO said (maybe too optimistic).
question Prof G: as fingolimod (with massive rebound after stopping it) and tecfidera did not really work i reached NEDA under OCR – would yo stop OCR because of Covid? age 37 with no other problems and still EDSS 0.
wouldn’t monoclonal antibody therapy, such as the combination regeneron product, be useful for recovery from covid19?
It has been shown over an over again that unless you treat early with anti-COVID-19 it doesnt do much…It is too late. Does this Sound famililar?
Le sigh….this is incredibly disheartening . Honestly teary here. So any hope for Covid vaccine response for a PwMS on ocrelizimab? “more effective than not being vaccinated at all”.
you write that data is coming….is it hiding?
Not hiding. T-cells studies are harder to do and more time-consuming. I am aware of several labs doing the work.
Re: T cell responses are harder and more expensive to do
Any chance that the COVID-19-specific Adapt-T T-cell test from Adaptive Biotechnologies will become a more accessible and affordable way to determine past COVID-19 exposure—either by natural infection or vaccination?
In the case registry of different countries, we can also observe some patients on anti-CD20 therapy, who have a practically asymptomatic covid infection. How can this be explained?
This is quite worrying. I’ve had both jabs. I knew response would be blunted but wanted to have them on paper if nothing else.
My son and family (who I haven’t seen for 18 mths) are coming to stay with me tomorrow, Welsh covid rules allow this. They haven’t been vaccinated as currently too young. I’ve been on Fingolimod for 4 years. I’m 59 and in relatively good nick. Am I putting myself in danger by having a family of 6 here?
It’s such a nightmare isn’t it? I hope neurologists work quickly to help patients on anti CD20 treatments to avail of alternatives just as they helped make changes to treatments available to patients during the pandemic – emergency changes were made for Cladribine and tysabri however neuros must be aware that further changes are now needed to allow eg a change to eg tysabri. Currently new spots are needed to be able change to tysabri. I’m battling this for a while now. Pls pls pls can you help effect this change ASAP? I have young children and do not feel safe on Ocrevus.
Yet there are patients in the studies on anti CD20 who have asymptomatic infection.
I am on anti CD20 and have a confirmed ‘strong positive’ antibody result to the spike protein following double vaccination.
If it is not B cells and now it seems it is also not T cells, how can either of the above be explained?
Excellent news what is the time between infusion and vaccination?
Did you have baseline cD19?
ProfG is usiually glass half full but today is half empty…50% of people made T cell response
T-cells blunted too? ? ? Rose tinted odometer 2 1/2 star max.
Please could you give the potted dummies version for me?
Is there any point getting the second dose? Will it do any good?
Wait for the data, stay calm and get vaccinated ASAP with both doses regardless of what DMT you are on. Is that simple enough?
indeed it is, thank you
after 6 OCR cycles and two jabs pfizer after 6 months from last dose there where no antibodies (value