COVID-19 and Autoimmune Demyelinating Diseases

Demyelinating Conditions Associated With Human Coronavirus Infection Before COVID-19

Viral infections can unsettle the body’s immune mechanism in several ways and can lead to immunosuppression in animals and humans. Several mechanisms are involved in viral-induced immunopathogenesis, such as impairment of T cell-mediated immunity, upregulation of MHC antigen expression, and molecular mimicry, resulting in overstimulation of B cells and/or T cells. The interaction of viruses with the host immune system is diverse and complex and has not been entirely elucidated. For example, studies have shown that mice infected with a neurotropic murine coronavirus [JHM mouse hepatitis virus (MHV-4)] show central nervous system (CNS) effects, such as acute encephalitis, chronic demyelination, and subacute paralysis.

SARS-CoV, HCoV-OC43, and HCoV-229E are human coronaviruses (HCoVs) with neurotropic and neuroinvasive properties and the potential to be neurovirulent. Association of HCoV infection with MS has been described, and coronavirus-like particles have been detected in autopsied brain tissue from MS patients and in mice infected with murine neurotropic CoV. Moreover, HCoV viral RNA and intrathecal production of anti-HCoV antibodies have been detected in autopsied brain tissues from patients with MS.

A study that assessed a large panel of human brain autopsy samples from donors who had various neurological diseases (25 nondiseased, 39 MS, and 26 other neurological disorders) reported a significantly higher detection of HCoV-OC43 RNA in MS patients (35.9%; 14 of 39) than in nondiseased donors (13.7%; 7 of 51). However, the presence of viral particles in the brain does not always mean that the virus has caused neurological pathology.

HCoV could induce CNS demyelination through several mechanisms, as has been shown in mouse studies, such as oligodendrocyte destruction, overexpression of cytotoxic antigens by glial cells, and overexpression of inflammatory markers (e.g., interleukin-1b, tumor necrosis factor, interleukin-6 [IL-6], and type 2 nitric oxide synthase). Other studies in rodents have shown the loss of myelin in the CNS during the acute phase of infection with murine coronavirus, with myelin degeneration occurring 2–3 weeks after infection.

In humans, a case of acute disseminated encephalomyelitis (ADEM) was reported in a 15-year-old patient who had upper respiratory symptoms secondary to HCoV-OC43 infection, where the virus was detected in cerebrospinal fluid (CSF) and nasopharyngeal samples. Also, a case of MERS-CoV infection-induced CNS demyelination was reported in a 71-year-old patient who developed inflammatory lesions in the periventricular deep white matter, corpus callosum, bilateral pons, midbrain, left cerebellum, and upper cervical cord that were detected on the 24th day of the disease.

The compelling evidence from studies in mice and observations in humans on the potential for coronavirus CNS involvement underlines the importance of assessing the potential for SARS-CoV-2 in not only causing CNS pathology but also exacerbating preexisting neurological disease during infection. Here, we present the effects of SARS-CoV-2 infection in patients with CNS autoimmune demyelinating disorders, and important considerations surrounding disease-modifying therapies (DMT) and their effects on the course of COVID-19. The main focus will be on multiple sclerosis and neuromyelitis optica spectrum disorder, the two most prevalent CNS demyelinating disorders, with brief discussions of other less common demyelinating diseases.

Multiple Sclerosis and SARS-CoV-2 Infection