Multiple Sclerosis (MS) is a chronic disease of the central nervous system where the immune system mistakenly attacks the myelin sheath, the fatty protective covering around nerve fibers. This damage disrupts the transmission of electrical signals, leading to a wide range of neurological symptoms. The emergence of SARS-CoV-2, the virus responsible for COVID-19, introduced a new variable into the understanding of autoimmune disorders. Scientists began investigating whether COVID-19 infection could act as an environmental trigger for MS. The core question is whether the powerful immune response generated against the virus might inadvertently initiate or accelerate this autoimmune condition in susceptible individuals.
How Viruses Can Trigger Autoimmunity
Viruses are recognized as potential environmental factors that can initiate autoimmune diseases like MS in people who are genetically predisposed. The body’s defense mechanisms against a pathogen can sometimes misfire, leading to an attack on its own tissues. One primary mechanism is called molecular mimicry. This occurs when a protein on the surface of the virus shares a structural similarity with a protein naturally found in the host body, such as myelin.
Immune cells, specifically T-cells and B-cells, are trained to identify and attack the viral protein. Because of the shared structure, these activated immune cells may lose their ability to distinguish between the invading virus and the host’s healthy cells. The resulting cross-reactivity causes the immune system to mistakenly target and damage the myelin sheath, potentially initiating the autoimmune process characteristic of MS.
Another pathway is known as bystander activation. When a viral infection occurs in the central nervous system, the resulting inflammation and damage can be intense. The immune system releases inflammatory molecules and chemicals to fight the infection, which can cause collateral damage to the surrounding tissue. This damage exposes previously hidden components of the host’s own cells, known as self-antigens.
The newly exposed self-antigens are processed by immune cells and presented as foreign threats, activating nearby T-cells that were previously dormant. This non-specific inflammatory environment lowers the threshold for activating autoreactive cells that might have otherwise remained inactive. Both molecular mimicry and bystander activation provide plausible explanations for how an infection like COVID-19 could theoretically set the stage for MS.
Research on New Multiple Sclerosis Onset After COVID-19
Epidemiological research investigating a link between SARS-CoV-2 infection and the onset of MS has focused on identifying new diagnoses following the pandemic. While numerous case reports document individuals developing MS symptoms shortly after infection, population-level data is necessary to establish a clear statistical association. A large-scale Swedish registry study examined the risk of MS diagnosis following COVID-19 infection between 2020 and 2022.
The analysis found that individuals who experienced severe COVID-19 requiring hospitalization had more than double the risk of a subsequent MS diagnosis compared to those not infected. The rate was approximately 26 new MS diagnoses per 100,000 patients who had severe COVID-19. The absolute risk remains extremely low, representing only about 0.02% of those with severe infection.
Researchers noted that less severe, non-hospitalized COVID-19 infections showed only a slightly increased risk that was not statistically significant after adjusting for other factors. This suggests that the severity of the inflammatory response, rather than the infection itself, may be the most relevant trigger. The intense inflammation seen in severe cases could be the driving force behind the bystander activation mechanism, potentially unmasking a latent autoimmune tendency.
The temporal relationship between the two events is complicated by the nature of MS, which can take many years to fully manifest after an initial trigger. Experts anticipate that the true effect of COVID-19 on MS incidence may become clearer only years from now, as the disease’s typical latency period is between 10 and 20 years from the initial exposure. Furthermore, computational modeling shows the SARS-CoV-2 virus possesses structural components that exhibit molecular mimicry with myelin proteolipid protein, a known target in MS.
Studies suggest that SARS-CoV-2 might indirectly trigger MS by reactivating other viruses, such as Epstein-Barr Virus (EBV), which is strongly implicated in MS development. The scientific consensus is that while COVID-19 is unlikely to be a common cause of MS, the intense inflammatory response it generates, especially in severe cases, can act as a non-specific trigger in susceptible individuals.
Managing COVID-19 in Existing Multiple Sclerosis Patients
For individuals already diagnosed with MS, a COVID-19 infection poses risks related to disease management and relapse. Any viral illness, including COVID-19, can trigger a relapse of MS symptoms or cause a temporary worsening of existing neurological function, known as a pseudo-exacerbation. Studies show that a notable proportion of MS patients who contracted COVID-19 experienced new or worsening neurological symptoms during their illness.
Management complexity centers on Disease Modifying Therapies (DMTs), which are designed to suppress or modulate the immune system to control MS activity. Certain highly effective DMTs, particularly B-cell depleting agents like ocrelizumab or rituximab, increase the risk of more severe COVID-19 outcomes, including hospitalization. These medications reduce the immune system’s ability to fight off the virus effectively and can significantly blunt the immune response to COVID-19 vaccines.
Conversely, some DMTs, such as injectable interferons or glatiramer acetate, are not associated with an increased risk of severe COVID-19 illness. Neurologists must balance the risk of severe COVID-19 against the risk of MS relapse if treatment is delayed or altered. Consensus guidelines recommend that vaccination against SARS-CoV-2 remains a high priority for all MS patients.
If a patient is on a DMT that reduces vaccine efficacy, timing the vaccine dose around the DMT infusion or cycle is necessary to maximize protection. Interrupting or delaying a highly effective MS treatment carries a substantial risk of disease reactivation, which is often considered a greater long-term threat than the COVID-19 risk, especially with current vaccination rates. Treatment decisions remain highly individualized, requiring close consultation between the patient and their care team.
Distinguishing MS from Other Post-COVID Neurological Issues
The primary challenge for clinicians is differentiating a true MS diagnosis or relapse from the neurological symptoms associated with the post-acute sequelae of COVID-19, often referred to as Long COVID. Symptoms such as profound fatigue, brain fog, sensory changes like tingling or numbness, and dizziness are common to both MS and Long COVID. This overlap necessitates a meticulous diagnostic approach.
The diagnosis of MS relies on demonstrating objective evidence of damage to the central nervous system that is characteristic of the disease and separated in both space and time. A brain and spinal cord Magnetic Resonance Imaging (MRI) scan is used for this, looking for specific demyelinating lesions that meet established diagnostic criteria. These lesions must show features of inflammation or scarring that are unique to MS.
A lumbar puncture is often used to examine the cerebrospinal fluid for the presence of oligoclonal bands, which are specific antibodies indicating chronic inflammation within the central nervous system. These objective findings distinguish a true demyelinating event from the transient, functional, or inflammatory neurological symptoms often seen in Long COVID. Without these specific imaging and laboratory markers, a patient’s symptoms are more likely attributed to a post-viral syndrome rather than the onset of MS.