Study Spotlight: COVID-19 and the Risk of CNS Demyelinating Diseases

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By Hannah Kelly

In a February episode of our “Ask the Expert” podcast, SRNA’s Rebecca Whitney and Dr. Michael Levy discussed his paper published in Frontiers of Neurology titled “COVID-19 and the risk of CNS demyelinating diseases: A systematic review.” During this conversation, Dr. Levy highlights key findings from the review article about the relationship between COVID-19 infections and both new diagnoses and relapses of central nervous system (CNS) demyelinating diseases, including Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorder (NMOSD), and MOG Antibody Disease (MOGAD). 

Dr. Levy starts by sharing, “NMO and MOG are both very rare disorders. It’s hard for one clinic to amass enough evidence to make a conclusion about something that happens in rare diseases, especially if you’re looking for a rare cause or rare trigger like COVID-19. So, what we did instead was we scoured the literature, everything including publications and posters, and other reports published in different platforms all around the world, in English that we could understand, where we confirmed the diagnosis, usually with aquaporin‐4 or MOG antibody testing. And then we looked for cases that were triggered after a COVID infection.”

Importantly, the rate of CNS demyelinating events occurring shortly after or at the same time as a COVID-19 infection was relatively low. Given the high global prevalence of COVID-19 infections, this suggests there probably was not anything specific about the COVID-19 virus that caused MS, NMOSD, or MOGAD. Instead, the virus likely provided a non-specific trigger to the immune system. Dr. Levy further explains that, “…just like with flu and vaccines, and basically anything that activates the immune system, COVID probably triggered this disease in someone who was already preparing to present and then this was the final straw.” 

For example, when the immune system fights off COVID-19, part of the virus might look similar to the MOG protein, which confuses the immune system and causes it to attack healthy MOG protein instead. Dr. Levy also mentions that studying NMOSD and MOGAD offers potential for determining these “mimicking triggers,” as we know the immune system specifically targets aquaporin-4 water channels and the MOG protein in NMOSD and MOGAD, respectively. 

The study did not consider transverse myelitis patients, as a previous study had already commented on the relationship between COVID-19 and transverse myelitis. Furthermore, Dr. Levy states that “with transverse myelitis, you’re always wondering, is that the first event of NMO or MOG or something else? You really need the benefit of retrospect over two or three years to really confirm the diagnosis of transverse myelitis.” Understanding the risk of idiopathic (without a clear cause) transverse myelitis will therefore become easier in the future as these cases are confirmed over time. 

It’s important to note that this study only captured published case reports, and there was likely a bias toward publishing cases of new NMOSD or MOGAD. According to Dr. Levy, “…the bias is toward new cases because there are probably a bunch of NMO and MOG patients who got COVID and then within the month may have had a relapse. Sometimes they don’t even know they had COVID and that wouldn’t be very exciting and so they probably wouldn’t publish it.” This study included patients of all ages, and because many children with COVID-19 never knew they had an infection, the study was probably also biased toward adult cases of CNS demyelinating events. 

Overall, this study emphasizes that just like the flu and other illnesses, COVID-19 activates the immune system in a way that may make someone with a CNS demyelinating disease more likely to have a relapse. Similarly, COVID-19 can make someone predisposed to autoimmunity present with a first attack of NMOSD or MOGAD. Patients not on immunotherapy for a CNS demyelinating disease should therefore be cautious in the face of COVID-19 and other infections. 

The podcast audio, video, and transcript are available in the Resource Library under the title “COVID-19 and the Risk of CNS Demyelinating Diseases.” You can access the published review article here.