What COVID may teach us about MS
A 28-year-old man recently went to a doctor complaining of sore throat, muscle aches, headache and an impaired sense of smell (Moore and colleagues. eNeurologicalSci 2021;22:100299). A COVID-19 test was negative. Over the next two weeks his malaise improved but he started to have episodes of dizziness, and his mouth felt numb when he brushed his teeth. He had episodes of dizziness and his vision became so “jumpy” that he could no longer watch TV or work on the computer. The vision problems were so troubling that he went to the Emergency Department.
A neurological exam confirmed that his right eye movements were not coordinated with his left eye (called ophthalmoplegia) and he had rapid, uncontrolled eye movements (called nystagmus). He was admitted to hospital. This time his nasal swab was positive, indicating that he had COVID-19. But there were other worrisome findings. An MRI showed numerous MS-like inflammatory lesions in his brain and a spinal tap showed banding in his cerebrospinal fluid, which indicated an immune reaction in his central nervous system (CNS). Possible CNS infections, such as herpes and syphilis, were ruled out. The doctors concluded that the man had two diagnoses: COVID-19 infection and multiple sclerosis. It appeared that in this case, COVID infection was associated with the development of MS.
This did not mean that COVID directly caused MS. In fact, there was no evidence that the CoV-2 virus that causes COVID had invaded the brain. But the case raised the possibility that a viral infection such as COVID-19 could trigger the onset of MS. The MS disease process likely had been ongoing – the MRI showed some older lesions – but it was the immune system’s response to the virus that unmasked the MS.
How direct a role do viruses play in the development of MS? Researchers have long speculated about this. In the 1940s, a coronavirus (similar to CoV-2) was shown to cause demyelination in an animal model of MS (Bailey and colleagues. J Exp Med 1949;90:195-212). In the 1990s, one of the pioneers of modern MS research, John Kurtzke (who developed the disability scale for MS, the EDSS, that is still in use today) suggested that infections could actually cause MS (Kurtzke and colleagues. Neuroepidemiology 1992;11:90-99). A follow-up suggestion that MS may be a sexually transmissible infection was hotly criticized and researchers have avoid this topic ever since (Hawkes CH. J Neurol Neurosurg Psychiatry 2002;73:439-443).
During the current pandemic, there have been several case reports of people developing demyelinating diseases after COVID infection (Zhang and colleagues. Medrxivorg, April 2020:21. Parsons and colleagues. J Neurol 2020;30:1-4. Reichard and colleagues. Acta Neuropathol 2020;140:1-6). Indeed, a second case of COVID-associated MS was recently reported in Spain (Palao and colleagues. Mult Scler Relat Disord 2020;45:102377).
It is well known that viral illnesses, such as a cold or flu, can cause a relapse-like worsening of MS symptoms because they stimulate an already overactive immune response. A similar mechanism may be at work with COVID-19. Indeed, it is generally assumed that a bout of COVID may well cause a worsening of MS symptoms (although not, strictly speaking, a relapse).
But the COVID pandemic may serve to rekindle interest in the larger question: the role of viruses in the development of MS. Is the problem the virus itself and, if so, are coronaviruses such as CoV-2 a greater or lesser concern than other viruses (such as the Epstein-Barr virus that has been linked to MS)? Is the timing of viral infection an issue, either because it occurs at a critical stage of immune development (as in adolescents) or at a juncture when an underlying problem may or may develop into MS (as in the case described above)? Or will COVID uncover an “immune signature” that predisposes someone to develop MS?
For the moment, the current wisdom is that people with MS are not more likely to contract COVID-19 than the non-MS population. However, it is important to note that viral infections interact with other factors. For example, several studies have reported that the immune system’s response to viral infections can be boosted with vitamin D supplements in people with MS (Najafipoor and colleagues. Cell Immunol 2015;294:9-12. Rolf and colleagues. Mult Scler 2018;24:1280-1287). So it may be worthwhile to take vitamin D supplements. The typical recommendation is to take 600 IU to 4000 IU per day. Since vitamin D levels are also boosted by sunshine, a little outdoor recreation would be a healthy choice once the weather becomes warmer (and the sun brighter). We can also hope that sun exposure will help to reduce the number of COVID cases over the spring and summer months.
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