#MSCOVID19: antibody testing post-vaccine

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Barts-MS rose-tinted-odometer: ★★★

Should I get an antibody test to prove that I have responded to the COVID-19 vaccine? No, you shouldn’t. Most diagnostic COVID-19/SARS-CoV-2 antibody tests are based on detecting antibodies to the so-called nucleocapsid protein and not the spike protein, which is the protein or immunogen used in the current vaccines. There are, however, a few private laboratories that are providing anti-spike protein antibody tests. However, antibody levels both from wild-type SARS-CoV-2 infection and the vaccine are not long-lasting and will wane with time. They also don’t tell us about T-cell responses. So even if you don’t seroconvert and are found to have no anti-spike protein antibodies post-vaccine you may still have immunity to the virus, which is likely to protect you from getting severe COVID-19. 

At the moment we don’t know what to do with the seroconversion information, i.e. in patients who don’t seroconvert do we revaccinate them? At the moment vaccinologists are saying no. I am a firm proponent of only doing tests as part of routine clinical practice if you are going to act upon them. As I won’t act on the information that somebody has or has not seroconverted post-vaccination I don’t want to know the result.

Yes, this information also applies to pwMS on anti-CD20 therapies (rituximab, ocrelizumab, ofatumumab) or S1P modulators (fingolimod, siponimod, ozanimod, ponesimod). I suspect when we see the data in pwMS on these two classes of therapy, those who don’t seroconvert will still have effector T-cell responses to the spike protein. Clearly, if the data shows I am wrong we will have to adapt our vaccination practice(s). This will then be evidence-based. However, until then #GetVaccinatedASAP

One can ask what have we learnt from the COVID-19 saga? As they say, hindsight is 20/20 or perfect vision. However, at the time the pandemic hit us I think we the MS community overreacted to the potential risks associated with SARS-CoV-2 and COVID-19 in relation to MS and DMTs and now we are overreacting to the vaccine readiness issue. 

It is quite clear from the study below that COVID-19 seronegative care home residents make a reasonably good anti-spike antibody response from the vaccine. This is telling me that they have immunological memory and that the immune system responds robustly to the vaccine. I see no reason why this won’t happen to pwMS on DMTs. Not having an antibody response or losing an antibody response to the SARS-CoV-2 be it from wild-type infection and/or a vaccine doesn’t mean you have lost your immunity to the virus; in all likelihood, it will be there to protect you from getting severe COVID-19. 

from JAMA

Blain et al. Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose. JAMA. Published online April 15, 2021. doi:10.1001/jama.2021.6042

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Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

40 comments

  • Thank‘s for that Prof G. As I (49, on Fingolimod since 2015) am getting my first Biontech Pfizer shot in 30 minutes, it is reassuring to read.

  • Thanks, much appreciated.

    Guess we will wait for someone to figure out the T-cell story. In the meantime, lets hope the pro plaguers (what anti-vaxxers really are) don’t get too much influence.

  • “I am a firm proponent of only doing tests as part of routine clinical practice if you are going to act upon them.”…..while I can understand your point of view, please note, some tests give the pwms comfort and control, despite not being actionable. For example, testing lymphocyte subsets are not part of routine clinical practice, yet several doctors including you, have advocated for routine monitoring of lymphocytes for certain DMTs. What about spinal MRIs? Some neurologist still do not perform these as routine care. Obviously, patient requests must be within reason and supportable.

    When I asked for a baseline of my cd19 before starting OCR, I was told it was not part of routine care. When I became allergic to OCR, I asked for ADA test, and was told no, even by the drug manufacturer. So without these tests, I do not know my normal level of cd19 (when it would be safe to start next DMT) and I do not know if I am allergic to OCR or all anti-cd20 drugs (so now I have to avoid all cd20 meds). So while some information might not be actionable today it might be very important later, under low probability high impact events. I just had this fight with my doctors about obtaining a detailed baseline of memory B cells before starting cladribine.

    • Re: “routine monitoring of lymphocytes”

      We monitor them as a very low lymphocyte level on certain DMTs may be needed to acted on.

      re: “spinal MRI”

      No, we don’t monitor MS disease activity with spinal MRI; it is too time and cost-intensive and rarely leads to a treatment change. The reason for this is that lesions come in clusters and if there is new MRI activity in the spinal cord there are usually new lesions in the brain. Lesions in the spinal cord are less likely to be asymptomatic. Saying this occasionally we do an MRI of the spine if there a specific question that needs to be answered.

      Please note a whole spine MRI is actually 3 regions or 3 MRIs. It takes the 20 minute scanning time, which is what happens for a brain MRI to over an hour. We simply can’t clog up the MRI system for information that is not going to change treatment decisions. Please note this is for monitoring and not the diagnosis.

      Re: “anti-CD19 and ADA”

      This is not routine, but if there is a concern around infusion reactions and non-response we would do these tests. But again we have to have a reason for doing them and we would then act on the result.

      • re:
        Re: “routine monitoring of lymphocytes”

        We monitor them as a very low lymphocyte level on certain DMTs may be needed to acted on.

        which ones? ty

    • Healthcare is also about value. We can’t be wasting NHS £ on tests that are not useful. We have a responsibility to the British taxpayer to run a cost-effective value-driven healthcare system.

      • Doctors might not act on cervical lesions; however, data shows individuals with spinal lesions are more likely to experience a more severe disease course. So when I am told I could be paralyzed from the neck down after an other severe attack in my cervical region, I want to monitor this region. This is actionable for me…..if I am more likely to become paralyzed in the future, then I need to do all I can now and not wait for later. Actionable to the patient.

        Glad your team tests for ADA, maybe you could share your tests with the greater MS community, since Barts is the only facility I know that does ADA testing. I tried to get my bloods to Dr. A, but none of my doctors wanted to go through all the red tape around mailing bloods across the pond.

        With respect to costs and time….I guess that is one of the few benefits of the private American healthcare system. We are not dictated by financial stewardship of public funds.

        As with all debates, there are two very reasonable arguments on both sides. Thanks for engaging 🧐

        • “Doctors might not act on cervical lesions; however, data shows individuals with spinal lesions are more likely to experience a more severe disease course. So when I am told I could be paralyzed from the neck down after an other severe attack in my cervical region, ”

          Yes..true the solution is action with hsct/alemtuzumab. Not more mri scans…by the time it shows on mri…it’s too late.

          • ANONS – Don’t forget to add cladribine to your list!

            HSCT/Alem are not the only DMTs that have a significant positive impact on disease progression. Arguably, Clad is the only drug currently approved that gets CNS penetration. So I will counter your HSCT/Alem suggestion with Clad, given the more favorable risk profile of Clad. Prof G. is even coining around to Clad (based on some of his recent posts).

            I agree, by the time I have cervical lesions it MIGHT be too late. However, even though I only had 3 full cycles of Ocr, it did stop and “heal” my exiting cervical lesions. Damage is done, but I feel starting with Ocr did significantly slow down my progession to a wheelchair.

            Plus HSTC is not approved in the US and I was denied access to the BEAT-MS clinical trial, due to safety concerns and my individual case. 50% get secondary autoimmunity with Alem, which is consideration that should not be overlooked.

      • Tell that the UK Government…aren’t you testing twice a week with the free lateral flow tests:-)…I still get £25 a PCR swab;-(

        • The lateral flow tests are not coming out of the NHS budget. I agree they are a total waste of money. Wasn’t this Dominic Cummings’ moonshot project?

          • Judging by the slew of revelations, I’d be surprised if someone in government or a close relative didn’t have a financial interest in the manufacturers of lateral flow tests.

  • Thank you for continuing to update us on this issue. I’m on Ocrevus and received the Pfizer vaccine here in the US. I was wanting to get the antibody test, not because there would be a clinical response, but so I could potentially re-enter society. If I were one of the few to produce antibodies and tested positive for said antibodies, I might be able to be around people again. What do you think about getting the test for those purposes?

    Second question – can I take any comfort in the fact that I had a reaction to the second dose? I had a fever for about 18 hours or so, peaking at 101.3f (38.5c).

    • I feel the same way. It might not be actionable in a healthcare kind of way but for me, personally, knowing that I made a response WOULD be actionable. Husband wants us to go visit his parents but I’m not about to get on an airplane without antibodies. Also not about to go back into the office without them either. I get my second shot next week and plan to ask for an antibody test. Furthermore, I plan to pay a few dollars out of pocket for this test: https://www.t-detect.com/. I’m also in the US so don’t quite have the same feelings about wasting healthcare dollars…

  • Thank you all so much for keeping patients up to date on this, this seems to be about the only resource online that is doing so. The US National MS Society will only share information like 6 months after it’s super super confirmed, and even engaged patients hit paywalls and knowledge ceilings. I’m optimistic for T-cell immunity (fingolimod here) but MAN would it be nice to see some evidence.

    • I hope there is central effector activity…based on B cell data with anti CD20 it is clear already that there are T cell responses when there is no seroconversion but I suspect that there are double T & B nonresponders

      • But when can we expect (at least preliminary) data on the T cell response in MSpeople on B-cell depleting treatment (e.g. Ocrevus)? Shouldn’t they already be out at least in countries such as Israel, UK and US? Is it that difficult to measure T cell response? Thanks you

        • Measuring T cell activity ismore difficult and it depends on whether you have the infrastructutre in place to do this. We did not have this in place when we started vaccinating so the opportunity was missed byus, but we know of other places doing T cells.

          In the UK dosing of immunosuppressed people started at the end of January…add 3months for the interval and that is end of April and two weeks to four weeks for antibody response and that puts you in May….In other countries you have one month between doses so I expect any time now.

          • Thanks for this very clear answer. Truly appreciated. Measuring and having information about the T cell response in people on b-cell depleting DMTs (such as Ocrevus) seems indeed the most important thing to do in this moment. Please keep us informed! By the way: since now, according to what you say, it is finally possible (at least in certain labs) to measure T-cell response, aren’t, in any part of the world, researchers measuring it also (or primary) in MSpeople on b-cell depleting DMTs who simply had got Covid during the past months? I understand it is not like measuring the T cell response to the vaccine, but assessing the T cell response in (for example) Ocrevus-treated people who had covid could have at least given us some ideas a on whether these individuals are able to mount a T cell response to Covid. In case of positive T cell response in such cases, indeed, we could have already speculated with a certain degree of confidence about the effectiveness of the Covid vaccines in such people too. Don’t you agree? Thansk!

  • I appreciate this is still new and evolving and say: ‘So even if you don’t seroconvert and are found to have no anti-spike protein antibodies post-vaccine you may still have immunity to the virus, which is likely to protect you from getting severe COVID-19.’

    Would it be an overreaction to take the ‘may’ and ‘likely’ as reasons why, for now, patients treated with ocrelizumab (other mabs?) need to continue behaving as though they are not vaccinated and have no protection?

    I appreciate the knowledge will firm up away from the ‘may’ and the ‘likely’ to something more definitive. As the expert do you have an insight into when it will be possible to make any more definitive statements?

    As a patient – reading between the lines of all this – I am interpreting this as I and others in the same boat will have to act as if we are still in lockdown. As a commonsense, not paranoid, measure.

    Do you agree or am I too concerned about a false issue?

    Thanks.

    • We do not know what a protective level of immunity is, but cancer studies have inpart already answered your questionand yes as long as you have T cells there is benefit. Maybe the challenge trials will address this.

      It is seems clear to me that either antibody responses are not generated or do not persist with some people, but the question is do such people get infected and if they do how quickly is the virus removed and what are the consequences. We will find this out in the next wave. There is already data from israel on post vaccine infection. I would maintain common sense and be cautious. If you are young you have a young immune system, its old farts like me that has cause for concern

  • I think this is a terrible dialectic on your part. Since we have no way to prove our T cell response, the only way to test response is spike protein. You say we MAY have T cell response. Those MS patients on anti CD 20 drugs should know if they are protected by the vaccine. There is a sense of protection and behaviors that differ once vaccinated. Despite your strong belief and vocal opinion of how low the risk to patients on anti CD20 therapies for severe COVID, it remains a risk nonetheless. There are many patients that do not seroconvert and the thought that there is a T cell response is just that, a thought. Until it can be proven, it is just more scientific supposition in a whirlwind of unknowns surrounding a new virus. “I am a firm proponent of only doing tests as part of routine clinical practice if you are going to act upon them. As I won’t act on the information that somebody has or has not seroconverted post-vaccination I don’t want to know the result.” The action of one of your patients not seroconverting is letting them know this information so they can protect themselves appropriately, since they MAY NOT be protected the same way you say they MAY be protected. So that they do not feel falsely protected. So they do not change their behaviors in an unsafe manner. Despite the lax way you discuss the risk to these patients, the risk remains, and they deserve to know their status!!

    • There are many patients that do not seroconvert and the thought that there is a T cell response is just that, a thought. Until it can be proven, it is just more scientific supposition in a whirlwind of unknowns surrounding a new virus.

      There are already a number of nonMS anti-CD20 studies that have surface, I think ProfG is partially correct

      • Do you have a sense of how time sensitive a T cell response to vaccination might be? Does it make sense to test T cell response to vaccination at 2-4 weeks like spike antibody? The study with the commercial test reports T-cell responses long (months) after Covid infections.

        • Testing for T cell responses on a large scale other than associated with a trial study is simply not feasible as it is much more complicated than tesing antibody responses.

        • In antibody tests you assay what is there but with T cell tests you stimulate to assay, so you test what you may respond to

  • I appreciate this post. As a patient I have to disagree on the assumption we will not act on the information. It is frustrating to see my vaccinated friends and family able to do more, shop without stress, have outdoor dinners with friends, while I still “must be cautious”. With an antibody and a T cell test (which I understand may be newly available?)- if there’s any protection I can at least be slightly less isolated than before as I’m no longer the only one. And more isolation means less walks, poorer mental health etc. which will worsen my condition. As i do not want covid but I also do not want to worsen my ms unnecessarily this information might change my daily habits. In addition many pwMS did not have the ability to time their vaccine to 12 weeks post infusion and may be overly cautious and more isolated than perhaps they need to be. Thirdly, the information will be valuable when boosters become available, and I suspect some of us would be first to qualify and need one. It would be helpful to know who needs it and who does not. If no testing, how else do individuals on b-cell depletion therapy as a DMT resolve the dilemma between not wanting to be isolated and not wanting to risk infection and possible relapse/long term damage?

    • With and antibody and T cell test…I guess the issue is know verse not knowing. I wanted to know and did not get the answer I wanted.

  • Perspective of a non-MD: One thing I DO know, is that when there already are differences of opinion, and there is a fog of information (about anything), people will pick out information which supports their opinion and claim they are correct (“right”).

    As eluded to by MSINTHEUS and others, being on Ocrevus and perhaps other DMTs appears at this time to lead to continued isolation and self-protection. Certainly no MD is going to say “take off your mask and have a good time!”. But that is just the reaction some PwMS are having- time it correctly and everything is fine. Truth be told, there are even more far reaching concerns that develop when one logically follows it out. First, if you are not concerned about the risk, do what you want, period. We already have plenty of that in The US and herd immunity will probably never be reached, not ever, so get that out of your mind. If you are concerned, yes, wear a mask, socially distance, etc. But be aware also, if you are concerned, being on O commits you- once in, you can’t “get out” for some time. You can’t change your mind, you’re “stuck”. If you are already on O, you are already “stuck”. So think a little deeper, if you are concerned: Who are your visitors and have they been vaccinated? Are they your children or grandchildren, and if so, who have they been hanging out with, the bar crowd?, a school that does not enforce masks or vaccinations? Will you be willing to wear a mask when most others have stopped doing so, thereby admitting visually to all there is something wrong with you, or “weak”, about you? How long will this go on? Not sure, but a good guess is probably your lifetime. Are you truly concerned and if so, are you really ready to do what you have to do to protect yourself? That is the conversation, in my opinion, doctors need to have with their patients.

    Roche, from my superficial perspective (which may not mean much), is already deep in the trenches with antibody testing, etc. The idea that they don’t have a test to tell you approximately where you are in terms of immune function, their medications and covid, is to me, is mind numbing. Yes, there are T cells and spike proteins and B cells and the whole thing is confusing and maybe you are protected somewhat anyway. I hate to say it, but there are more important things than fighting MS when you have MS. As an example, the CDC just temporarily halted the J&J vaccine in the midst of deadly pandemic where the number of vaccines correlates directly to number of deaths. That’s a huge reaction to a tiny problem. So what should Roche be doing? Something to me, doesn’t particularly smell “too fresh”. So I elude back to my opening point- people will pick out information that supports their pre-existing position on an issue which supports their own purpose, not yours. There are other medications, if you are concerned.

    • Two additional points I failed to mention, is that if you are concerned, people on O shouldn’t be hanging around with other people on O. Just an ironic observation. And wearing a mask at work? Co-workers and customers will gossip and some bosses will treat you differently no matter how illegal that is. It’s just the truth, ask any black or handicapped person. I won’t add to the list but I’m sure you can if you stop and think about it.

    • OK, one more. Keep the mask on also, because you may now be a potential “speader”, being potentially immuno-compromised. Maybe not, but maybe…can’t tell and can’t say either way for sure. Try that one at work a year from now with your mask on.

      • Can you maybe explain what the take away from all your fear-mongering is (not saying these concerns do not apply – to SOME degree)?

        Drop anti cd20 for something else hoping that vaccination will be more effective there?
        We’re all f***ed?
        Something else I am missing?

          • Somehow the comment from early morning does not seem to have made it. On rereading, I wanted to apologize to Tom for the ‘fear^mongering’, that was over the top.

            Still, would like to hear what drives his (in my view overstated) pessimism and what he concludes from it all.

          • I’ve tried a few responses for you, all respectful, and looked at them, and just have to step back as Mouse Doctor requested. But I do thank you for the initial comment.

  • Sorry Prof G! I’m on Fingolimod and out of morbid curiosity I paid to one of the private clinics to have the antibody test just over two weeks after having my second Astra Zeneca vaccine. I came out as positive as had >50. 115 AU/ml to be exact. Was advised most folk are in the upper 1000s….as high as 80000. Comforting I am positive but as expected very low. Very interesting reading all the latest information on this blog, poor old Fingolimod coming out as 0. It was great for me the time I started on it almost 10 years ago as no side effects unlike Rebif which I was injecting 3 times a week before. and felt permanently rubbish!

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