Case study: Did COVID-19 trigger the onset of my MS?
Many people who developed MS quite soon after COVID-19 or after receiving a COVID-19 vaccine are likely to question whether or not their disease was caused by either the infection or the vaccine.
Case study
Professor Giovannoni, I am 32 years of age and developed my first MS symptoms seven months after the birth of my daughter and about six weeks after having COVID-19. I had two AstraZeneca COVID-19 vaccines in 2021 and a third COVID-19 vaccine during pregnancy. I have severe flu-like symptoms and fatigue after the vaccines and now have symptoms of long COVID-19. I am convinced that the vaccines and/or COVID-19 triggered my MS. Is there any way to prove this?
Prof G’s opinion
It is typical for people diagnosed with MS to examine recent events and their life and look for triggers that can relate to their MS onset. This is a natural thing to do, particularly when the scientific and medical professions can’t say why you developed MS; you try finding answers yourself. This is why many people who developed MS quite soon after COVID-19 or after receiving a COVID-19 vaccine are likely to question whether or not their disease was caused by either the infection or the vaccine.
In the UK, the incidence of MS is quite high, with approximately 8 newly diagnosed people with MS per 100,000 population. With a total population of ~68 million people, there will be 5,000-6,000 new cases of MS per year in the UK. During the pandemic, many of these pwMS will have developed their MS shortly after having COVID-19 and/or receiving a COVID-19 vaccine. Hence, many people with recently diagnosed MS think COVID-19 or the COVID-19 vaccine caused their MS. However, the data argue against this.
Firstly, when people present with their initial symptoms, most will have had asymptomatic MS for years already. Approximately 70% of people presenting with their initial attack will have old lesions on their scan compatible with demyelination and MS that predate the COVID-19 pandemic. Yes, MS doesn’t just appear. We think it takes years to develop manifest or symptomatic MS.
When you look at large databases, there is no increased incidence of MS after either COVID-19 or the COVID-19 vaccines (see figures and paper 1 below). In comparison, there does appear to be an increased incidence of several other autoimmune diseases after COVID-19. These studies are very well done and are an example of the power of big data in exposing these sorts of links.
I find it interesting that many autoimmune diseases are increased after COVID-19, but not MS. Is this telling us something about MS. Could MS not be an autoimmune disease? Could it be due to an infection unrelated to COVID-19, for example, EBV? This is my interpretation of the data. I have been saying for years that MS is not autoimmune. The autoimmune hypothesis of MS is based on animal models and is not proven.
Interestingly, the few cases presenting with demyelinating syndromes after COVID-19 vaccination are not typical MS and tend to be transverse myelitis or neuromyelitis optica (see papers 2 & 3). The small number of incident MS cases presenting after vaccination have had pre-existing old lesions suggesting MS predating them receiving the vaccine. Therefore, it is doubtful that COVID-19 vaccines cause MS or even act as a trigger of MS.
It is apparent from the pre-DMT era that relapses or MS attacks can be triggered by infections. It is important to realise that the signal of infections triggering relapses is not apparent in pwMS on DMTs. We have to assume that the DMTs are preventing these infection-related relapses. So in people who have asymptomatic MS or have MS and are not on DMTs, it would not be surprising if there was a relationship between COVID-19 and potentially the vaccine and the initial attack or relapse. A recent meta-analysis has demonstrated this relationship (see paper 4 below). Please note that the association is small and is likely to be affected by publication bias, i.e. positive studies tend to get published. In comparison, negative observations don’t get analysed, negative papers don’t get written and submitted, and even if they are submitted, they aren’t accepted for publication. This publication bias inflates the apparent risk of relapse after vaccination and/or SARS-CoV2 infection. In comparison, pseudorelapses due to temperature-related conduction block are much more common and shouldn’t be confused with relapses.
For more information on pseudo-relapses, please read my Newsletter, “Am I having a relapse? (5-Jan-22)”.
The flu-like symptoms you had after your COVID-19 vaccines were due to the inflammatory response to the vaccine and are not uncommon. During the pandemic, many of my patients with MS developed flu-like symptoms, and I suspect pwMS are prone to these types of side effects. Part of MS-related fatigue is sickness behaviour in response to the inflammation in the brain and spinal cord from having MS. I suspect pwMS may have a lower threshold to developing flu-like symptoms when they develop systemic inflammation in relation to infection or vaccination.
I note you now have a long COVID-19. Are you sure this is not simply MS-related fatigue? I find diagnosing long COVID in pwMS difficult because the symptoms that define long COVID are the same symptoms associated with MS-related fatigue.
I think long COVID is more than one condition and represents an overlap syndrome between people with severe infection and end-organ damage involving the lung, heart and possibly brain. Many patients who spend prolonged time on a ventilator acquire damage to many organ systems. Therefore it is not surprising they have long COVID. On the other side of the spectrum, there are people who have a relatively benign self-limiting COVID-19 and are left with post-viral fatigue syndrome. This syndrome is not new and occurs after many viral infections, including influenzae, infectious mononucleosis, hepatitis, etc. The mechanisms underpinning post-viral fatigue overlap with the same mechanisms that cause MS-related fatigue. This why differentiating whether or not you have long COVID or MS-related fatigue syndrome is a moot point. For more information on the work-up and management of MS-related fatigue, please read my prior newsletters on this topic.
I don’t think the COVID-19 vaccine or COVID-19 caused your MS. COVID-19 may have triggered MS disease activity, but non-specifically. I suspect the onset of your MS likely predated COVID-19. Your long COVID may be MS-related, so you need a work-up and management of your MS-related fatigue. For example, if you are not on a disease-modifying therapy, you may need to start one to suppress ongoing inflammation and sickness behaviour. In addition, you need a detailed clinical work-up and investigations to exclude other causes of fatigue.
I hope this helps. I would be interested to hear if other readers have had similar experiences.
Paper 1
Background: There are a growing number of case reports of various autoimmune diseases occurring after COVID-19, yet there is no large-scale population-based evidence to support this potential association. This study provides a closer insight into the association between COVID-19 and autoimmune diseases and reveals discrepancies across sex, age, and race of participants.
Methods: This is a retrospective cohort study based on the TriNetX U.S. Collaborative Network. In the test-negative design, cases were participants with positive polymerase chain reaction (PCR) test results for SARS-CoV-2, while controls were participants who tested negative and were not diagnosed with COVID-19 throughout the follow-up period. Patients with COVID-19 and controls were propensity score-matched (1: 1) for age, sex, race, adverse socioeconomic status, lifestyle-related variables, and comorbidities. The primary endpoint is the incidence of newly recorded autoimmune diseases. Adjusted hazard ratios (aHRs) and 95% confident intervals (CIs) of autoimmune diseases were calculated between propensity score-matched groups with the use of Cox proportional-hazards regression models.
Findings: Between January 1st, 2020 and December 31st, 2021, 3,814,479 participants were included in the study (888,463 cases and 2,926,016 controls). After matching, the COVID-19 cohort exhibited significantly higher risks of rheumatoid arthritis (aHR:2.98, 95% CI:2.78-3.20), ankylosing spondylitis (aHR:3.21, 95% CI:2.50-4.13), systemic lupus erythematosus (aHR:2.99, 95% CI:2.68-3.34), dermatopolymyositis (aHR:1.96, 95% CI:1.47-2.61), systemic sclerosis (aHR:2.58, 95% CI:2.02-3.28), Sjögren's syndrome (aHR:2.62, 95% CI:2.29-3.00), mixed connective tissue disease (aHR:3.14, 95% CI:2.26-4.36), Behçet's disease (aHR:2.32, 95% CI:1.38-3.89), polymyalgia rheumatica (aHR:2.90, 95% CI:2.36-3.57), vasculitis (aHR:1.96, 95% CI:1.74-2.20), psoriasis (aHR:2.91, 95% CI:2.67-3.17), inflammatory bowel disease (aHR:1.78, 95%CI:1.72-1.84), celiac disease (aHR:2.68, 95% CI:2.51-2.85), type 1 diabetes mellitus (aHR:2.68, 95%CI:2.51-2.85) and mortality (aHR:1.20, 95% CI:1.16-1.24).
Interpretation: COVID-19 is associated with a different degree of risk for various autoimmune diseases. Given the large sample size and relatively modest effects these findings should be replicated in an independent dataset. Further research is needed to better understand the underlying mechanisms.
Paper 2
Background: Since the emergency use approval of different types of COVID-19 vaccines, several safety concerns have been raised regarding its early and delayed impact on the nervous system.
Objective: This study aims to systematically review the reported cases of CNS demyelination in association with COVID-19 vaccination, which has not been performed, to our knowledge.
Methods: A systematic review was performed by screening published articles and preprints of cases of CNS demyelination in association with COVID-19 vaccines in PubMed, SCOPUS, EMBASE, Google Scholar, Ovid and medRxiv databases, until September 30, 2021. This study followed PRISMA guidelines. Descriptive findings of reported cases were reviewed and stratified by demographic and clinical findings, diagnostic work-up, management, and overall outcome.
Results: A total of 32 cases were identified, with female predominance (68.8%) and median age of 44 years. Eleven cases were reported after Pfizer vaccine, 8 following AstraZeneca vaccine, 6 following Moderna, 5 following Sinovac/ Sinopharm vaccines, and one following each of Sputnik and Johnson&Johnson vaccines. The majority of cases (71.8%) occurred after the first dose of the vaccine, with neurological symptoms manifesting after a median of 9 days. The most common reported presentations were transverse myelitis (12/32) and MS-like pictures (first diagnosis or a relapse) in another 12/32 cases, followed by ADEM- like (5/32), and NMOSD- like (3/32) presentations. History of a previous immune-mediated disease was reported in 17/32 (53.1%) cases. The mRNA-based vaccines resulted in the greatest number of demyelinating syndromes (17/32), followed by viral vector vaccines (10/32), and inactivated vaccines (5/32). Most MS-like episodes (9/12) were triggered by mRNA-based vaccines, while TM occurred following both viral vector and mRNA-based vaccines. Management included high dose methylprednisolone, PLEX, IVIg, or a combination of those, with a favorable outcome in the majority of case; marked/complete improvement (25/32) or stabilized/ partial recovery in the remaining cases.
Conclusion: This systematic review identified few cases of CNS demyelination following all types of approved COVID-19 vaccines so far. Clinical presentation was heterogenous, mainly following the first dose, however, half of the reported cases had a history of immune-mediated disease. Favorable outcome was observed in most cases. We suggest long-term post-marketing surveillance for these cases, to assess for causality, and ensure the safety of COVID-19 vaccines.
Paper 3
Following the COVID-19 virus epidemic, extensive, coordinated international research has led to the rapid development of effective vaccines. Although vaccines are now considered the best way to achieve collective safety and control mortality, due to the critical situation, these vaccines have been issued the emergency use licenses and some of their potential subsequence side effects have been overlooked. At the same time, there are many reports of side effects after getting a COVID-19 vaccine. According to these reports, vaccination can have an adverse event, especially on nervous system. The most important and common complications are cerebrovascular disorders including cerebral venous sinus thrombosis, transient ischemic attack, intracerebral hemorrhage, ischemic stroke, and demyelinating disorders including transverse myelitis, first manifestation of MS, and neuromyelitis optica. These effects are often acute and transient, but they can be severe and even fatal in a few cases. Herein, we have provided a comprehensive review of documents reporting neurological side effects of COVID-19 vaccines in international databases from 2020 to 2022 and discussed neurological disorders possibly caused by vaccination.
Paper 4
Background: Concerns about vaccination increased among patients with multiple sclerosis (MS) regarding side effects, efficacy, and disease exacerbation. Recently there were reports of MS relapses after the COVID-19 vaccination, which emerged the safety concerns. Therefore, we aimed to perform a systematic review of case reports and case series studies to investigate the MS relapses after COVID-19 vaccination with most details.
Methods: We systematically searched three databases, including PubMed, Scopus, and Web of Science, in February 2022. Case reports and case series which reported relapse after COVID-19 vaccination in MS patients were eligible to include in our study.
Results: Seven studies were included in our systematic review after the abstract and full-text screening with a total of 29 cases. The mean duration between COVID-19 vaccination and relapse appearance was 9.48 ± 7.29 days. Among patients, 22 cases experienced relapse after their first dosage of the COVID-19 vaccine, one after the second dose, and five after the booster dose. The type of vaccine was unknown for one patient. The most common symptoms of relapses were sensory deficits (paresthesia, numbness, dysesthesia, and hypoesthesia) and weakness.
Conclusion: Overall, the COVID-19 vaccination may trigger relapses in some MS patients, but as the infection itself can stimulate relapse, the benefit of vaccination outweighs its risk in this population, and mass vaccination against COVID-19, especially in MS patients, should be continued and encouraged.
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
I loved this example and response. I also am SO happy you stated you do not believe MS is an autoimmune illness. I think framing it as an autoimmune disease makes it seem less serious and decreases urgency to cure. I am a marketer and many would be surprised at the power of branding and strongly believe that reframing MS as a virus that never leaves your body and attacks and shreds your brain and spinal cord even while everything seems “fine” will lead to a very different attitude towards this disease and hopefully improve patient outcomes
Just a future request
I’d love to see something about vaccines. The rise of anti vaxers and increase in mosquito borne viruses makes me nervous for the long term
More and more young parents aren’t getting kid’s vaccines which is shocking to me
As an MS community I’m seeing this thinking seep into social media groups and knowing ebv is the trigger we all want a vaccine for ebv (+ treatment for those of us already with MS) how are we going to convince the wider public + pwMS to take this vaccine?