#MSCOVID19: coronavirus vaccine linked to MS-like complications

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You will have heard by now that AstraZenca has paused its coronavirus vaccine study because of safety concerns. A study subject who received the vaccine developed transverse myelitis and had to be admitted to hospital. 

“The woman’s diagnosis has not been confirmed yet, but she is improving and will likely be discharged from the hospital as early as Wednesday”, said Soriot AstraZenca’s CEO (source STAT News).

From the same press conference, we also found out that another study subject had developed multiple sclerosis after receiving the vaccine. As most of you are aware transverse myelitis may be the initial manifestation of MS and sometimes it is very difficult to differentiate non-MS related transverse myelitis from CIS (clinically isolated syndrome compatible with demyelination or MS). 

Are two swallows enough to make a summer? I suspect not and I would be surprised if the data and safety monitoring committee recommends stopping the trials. However, they may do so if there is a third or fourth case. 

Transverse myelitis (TM)  is well described after vaccination as well as after viral and other infections. The yellow fever vaccine is probably the most common cause of vaccine associated TM. However, it was a common adverse event with the original rabies vaccine that was cultured and isolated from monkey neuronal cells. Fortunately, this is not how the rabies vaccine is made anymore and the incidence of TM is now much less common after rabies vaccination. Other vaccines that can trigger TM are influenzae, MMR, Japanese B encephalitis, hepatitis B and HPV vaccines. TM has also been associated with many infections, particularly viral and some bacterial infections. We neurologists refer to this type of TM as being vaccine-associated or post-infectious TM, respectively. 

Even if the AstraZenca vaccine trials restart, which in my opinion is likely, and the vaccine is shown to be effective, it is likely that the regulatory authorities will include TM as a potential adverse event. The latter will be based on the recent case and the historical perspective of other vaccines being known triggers of TM. What they will do about the case of MS is anyone’s guess, but I suspect they will include triggering MS disease activity as a potential adverse event as well. If they do this this will cause the MS community to probably err on the side of safety and hence this particular coronavirus vaccine will not be recommended for people with MS. 

Other implications is that there is a chance that the TM has not been induced by the Chimpanzee Adenovirus vector that is being used in this vaccine, but the actual coronavirus spike protein or immunogen. It is noteworthy that several cases of COVID-19 related TM have already been reported in the literature (see below), suggesting it may be the virus or the spike-protein that is the culprit.  If this proves to be the case then it is really bad news as TM will be a problem for the whole class of vaccines using the spike protein as the immunogen. 

So the implications of these observations are enormous for the field. However, there are things that can be done by neuroimmunologists to study the immune response to the SARS-CoV-2 spike protein and the Chimpanzee Adenovirus vector to see if there is any cross-reactivity with proteins and lipids in the spinal cord. The latter are standard molecular mimicry studies and this could help AstraZeneca and other vaccine manufacturers understand the TM risk in more detail.

You have to realise that this is what happens with vaccine and drug development and underscores why drug and vaccine development is so risky and expensive. The investment costs in terms of this vaccine have been largely derisked for AstraZenca by most of the preclinical development being funded and done by academia and the fact that the British and other governments have pre-ordered millions of doses of vaccine. 

We will update you on this story as it evolves. 

Addendum: the published case reports of TM-like conditions occurring in association with COVID-19.

1.Acute transverse myelitis after COVID-19 pneumonia.Munz M, Wessendorf S, Koretsis G, Tewald F, Baegi R, Krämer S, Geissler M, Reinhard M.J Neurol. 2020 Aug;267(8):2196-2197. doi: 10.1007/s00415-020-09934-w. Epub 2020 May 26.PMID: 32458198 Free PMC article. No abstract available.
2.Transverse Myelitis in a Child With COVID-19.Kaur H, Mason JA, Bajracharya M, McGee J, Gunderson MD, Hart BL, Dehority W, Link N, Moore B, Phillips JP, Rogers D.Pediatr Neurol. 2020 Jul 29;112:5-6. doi: 10.1016/j.pediatrneurol.2020.07.017. Online ahead of print.PMID: 32823138 Free PMC article. No abstract available.
3.Acute transverse myelitis in COVID-19 infection.Chow CCN, Magnussen J, Ip J, Su Y.BMJ Case Rep. 2020 Aug 11;13(8):e236720. doi: 10.1136/bcr-2020-236720.PMID: 32784242 Free PMC article.
4.COVID-19-associated acute transverse myelitis: a rare entity.Chakraborty U, Chandra A, Ray AK, Biswas P.BMJ Case Rep. 2020 Aug 25;13(8):e238668. doi: 10.1136/bcr-2020-238668.PMID: 32843475 Free PMC article.
5.Transverse myelitis related to COVID-19 infection.Zachariadis A, Tulbu A, Strambo D, Dumoulin A, Di Virgilio G.J Neurol. 2020 Jun 29:1-3. doi: 10.1007/s00415-020-09997-9. Online ahead of print.PMID: 32601756 Free PMC article. No abstract available.
6.COVID-19-associated acute necrotizing myelitis.Sotoca J, Rodríguez-Álvarez Y.Neurol Neuroimmunol Neuroinflamm. 2020 Jun 10;7(5):e803. doi: 10.1212/NXI.0000000000000803. Print 2020 Sep.PMID: 32522767 Free PMC article. No abstract available.
7.Acute necrotizing myelitis and acute motor axonal neuropathy in a COVID-19 patient.Maideniuc C, Memon AB.J Neurol. 2020 Aug 9:1-3. doi: 10.1007/s00415-020-10145-6. Online ahead of print.PMID: 32772172 Free PMC article.
8.A case of possible atypical demyelinating event of the central nervous system following COVID-19.Zoghi A, Ramezani M, Roozbeh M, Darazam IA, Sahraian MA.Mult Scler Relat Disord. 2020 Jun 24;44:102324. doi: 10.1016/j.msard.2020.102324. Online ahead of print.PMID: 32615528 Free PMC article.
9.Acute transverse myelitis associated with SARS-CoV-2: A Case-Report.Valiuddin H, Skwirsk B, Paz-Arabo P.Brain Behav Immun Health. 2020 May;5:100091. doi: 10.1016/j.bbih.2020.100091. Epub 2020 Jun 6.PMID: 32835294 Free PMC article.

CoI: multiple

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.

41 comments

  • If TM is associated with the many vaccines listed above should PwMS be having any of them? We are usually advised the flu vaccine is important and it is always stressed because it is not live it is not a risk.

  • COVID-19 seems to be at least some extent neuroinvasive destroying CNS tissue much like the ZIKA virus.
    The difference here being however that there doesn’t seem to be much of an immune response in the brain.

    So wouldn’t one treatment target of any vaccine be to stimulate such a response on purpose thus triggering unintended AE such as autoimmune reactions?

    Abstract
    Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

    https://www.biorxiv.org/content/10.1101/2020.06.25.169946v2

  • So do you think that a covid vaccine could exacerbate existing MS?

    Also in this article are you saying that influenza vaccines are a problem?

    I am confused

    Finally if the vaccine is deemed safe and was available this side of Christmas would it be able to be be administered close to the usual annual flu jab?

  • I had a Yellow Fever vaccination in the spring of 1999, I had my first MS episode during the summer that followed but have never seriously thought there was a connection until reading this. I was diagnosed with Transverse Myelitis in the spring of 2001, and that changed to an MS diagnosis in 2005. Now I feel a very deep sadness that I my have unwittingly caused my own health problems and brought such worry to my family.

    • Please try not to beat yourself up about this Catherine .
      Most of us with MS can identify the things we’ve done that maybe pertinent to having the disease.
      For myself I can reference low level smoking and even extensive use of sunscreen after friend died of skin cancer (lack of VitD)
      From what ProfG says in the comments your TM wasn’t triggered by the YF vaccine.
      The ‘blame game’ is all too prevalent with any health issues these days – what haven’t you/I done? What did you/I do?
      Living with MS is more than enough of a challenge and the fact you read this Blog evidences your interest in being knowledgeable about it, and are likely to be focussed on living as well as you can too!

  • If it’s the spike protein, the coronavirus SARS-CoV-2 itself could also trigger TM?

    The influenza vaccines causing problems – these are not the ones used for flu jabs?

    • The issue with the flu vaccine is that it changes each year as the strains change. So a vaccine that may trigger autoimmunity one year may never do it again. For example, the increased risk of narcolepsy that was found following vaccination with Pandemrix, the monovalent 2009 H1N1 influenza vaccine in 2009, has not been seen again.

      This is why we assume the current, or next, flu vaccine is safe until proved otherwise.

      • I developed ITP following routine flu vaccine 2 years ago. I had been treated with alemtuzumab 6 & 7 years previously so had a good idea what was going on straight away, but was blaming alemtuzumab.
        The haematologist who treated the ITP recommended future flu vaccines due to the changes each year, he sees this reaction from time to time. My neurologist told me to never have a another one, flu not nice but less risky than ITP. Who’s advice to follow…?
        I haven’t had the last 2 flu vaccinations, this year included, but it is not a decision I have made lightly.

    • Re: “If it’s the spike protein, the coronavirus SARS-CoV-2 itself could also trigger TM?”

      Yes, there have quite a number of cases of COVID-19 associated transverse myelitis reported already.

    • It won’t turn you into either a chimpanzee or a monkey, Mary, 🙂 though I’m sure the anti-vaxers would tell you different.

  • (aside from ‘assuming that a particular strand of flu vaccine is safe until proved otherwise’) is it reasonable to expect, more generally, that PwMS using DMTs such as glatiramer acetate, beta-interferon, DMF, teriflunomide, have a somewhat lesser risk when having influenza vaccines?
    Or, conversely, that PwMS who have discontinued such a DMT are at a slightly elevated risk?

    • Each flu vaccine goes through safety checks first, but until you release it onto the market and vaccinate millions of people are these very rare events seen.

      There have been several studies of flu vaccination in pwMS and they have shown the vaccines to be safe and not to trigger MS disease activity on MRI or clinically. The issue is that flu vaccines change with each season so what may be very safe last season doesn’t necessarily apply to next year.

  • What is the delay between the yellow fever vaccine and onset of TM? I had the vaccination (I belief) with a serious of others in 2005 and five years later I developed TM. Is that two far away to be causal?

  • Re
    Transverse myelitis (TM) is well described after vaccination as well as after viral and other infections.

    1. How does neurologist tell the difference between CIS / MS relapse and TM from a vaccine / infection?
    Out of all the people vaccinated, what chance someone happens to have a relapse at that same time? Ie TM would have occurred regardless?

  • Thanks for sharing this update and the MS perspective on it and of course to all those involved in the trials.
    I appreciate there are people who sadly suffer with specific organ damage (lung/heart etc) after covid19, but a lot of the other effects of “long covid” do sound remarkably familiar.
    You say there is a chance that it is the coronavirus spike protein or immunogen that caused TM and if that is the case, this particular vaccine may not be recommended for PwMS.
    But then presumably it is not just the vaccine that carries this risk, but also having covid itself. So do you think this will lead to a review of how vulnerable PwMS are to covid? Will it still be differentiated on the basis of which DMT we are on?

  • Infective acute transverse myelopathy. Report of two cases.
    Linssen WH, Gabreëls FJ, Wevers RA.
    Neuropediatrics. 1991 May;22(2):107-9. doi: 10.1055/s-2008-1071427

    Adenovirus myelitis and Epstein-Barr myelitis: two unusual viral causes with similar presentations].
    Breteau G, Stojkovic T, De Seze J, Gauvrit J, Pruvo J, Vermersch P.
    Rev Neurol (Paris). 2000 Sep;156(8-9):786-9.

    ADENOVIRUS AS A CAUSE OF TRANSVERSE MYELITIS IN THE INTENSIVE CARE UNIT
    October 2008Chest 134(4_MeetingAbstracts)
    DOI: 10.1378/chest.134.4_MeetingAbstracts.c36002
    Authors:

  • Interesting article, as soon as I heard a volunteer on vaccine trials had developed TM I was concerned. In 2018 (as a healthy 65 year old), and 3 weeks after having my top up vaccines for travel abroad, I was developed GBS, Guillian Barre Syndrome which is similar I think to TM, Epstein Barr.? The myelin sheath protecting my nerve endings had been damaged so was partially paralysed, it started as a spinal cord inflammation.

    Luckily I was back in UK but still took nearly 3 weeks for doctors to diagnose as wasn’t totally paralysed!!! After IVIG for 5 days (at massive cost to NHS) I began to recover but it was a long slow process. By eliminaton I was told it was my vaccines that caused my immune system to break down and not to have a vaccination again.

    Have any of the Covid patients had GBS ??

    • Re: “Have any of the Covid patients had GBS?”

      Many. We have had a few cases at our hospital and there are now a few published cases series.

      Trujillo Gittermann et al. Relation between COVID-19 and Guillain-Barré syndrome in adults. Review Neurologia. 2020 Jul 24;S0213-4853(20)30230-9. doi: 10.1016/j.nrl.2020.07.004.

      Introduction: Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this association and its implications. The objective of this review is to analyse the available evidence on this topic in the adult population.

      Material and methods: A systematic review was conducted of studies published on scientific databases: PubMed, Cochrane, Science Direct, Medline, and WHO COVID-19 database.

      Results: We identified 45 studies, which were analysed and completed using the Covidence platform; the final analysis included 24 articles, with a total of 30 patients.

      Conclusions: We found a strong association between both conditions; furthermore, the studies analysed highlight differences in the presentation of the disease, with greater severity of symptoms in Guillain-Barre syndrome associated with COVID-19.

  • Are you aware of a paper published in 2000 in the Journal of Virology and titled “Neuroinvasion by Human Respiratory Coronaviruses” it was observed that upper respiratory tract infections of viral origin could be an important trigger of MS attacks.
    In another paper published in 2019 in the journal Viruses and titled “Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?” it was observed that several respiratory viruses have neuro-invasive capacities, being able to spread from the respiratory tract to the central nervous system (CNS). The general thinking is that coronaviruses infecting the human CNS (Central Nervous System) can lead to long-term neurological diseases. The 2010 paper put it in this way:
    “Like other well-recognized neuro-invasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology).”
    The author of both papers Dr. Pierre Talbot, Director of the Laboratoire de neuroimmunovirologie at Armand-Frappier Santé Biotechnologie research centre in Laval (north of Montréal, Québec, Canada.) Over several decades Dr. Talbot has authored several academic papers including the above two which look at the coronavirus and its possible role in MS.

  • In 2001, after only one dose of hepatitis B vaccine I started with multiple sclerosis. Now I continue with MS problems and I am using rituximab treatment. I have afraid with this new problem in the covid vaccine. Why some vaccines can induce neurological problems? Virus, adjuvants, etc?

  • I developed Optic Neuritis following 1 dose of Hepatitis B. 4 years later a Hepatitis A vaccination led to hospitalisation with TM and a diagnosis of MS. 3 years later, a full course of Hepatitis B and I was back in a wheelchair again. I was a nurse so was expected to have the Hep B for work, even after highlighting concerns over previous adverse reactions to these vaccines.

  • About 18 years or so ago,I had terrible arthritis,often having to use a walking stick and in a lot of pain,along came a ground breaking new injectable drug,HUMIRA. It did wonders for my arthritis but after a few months I developed ms and my rheumatologist couldn’t take me off it quick enough .

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