Neurologic complications associated with SARS-CoV-2 have been reported with retrospective studies identifying between 14%–67% patients experience neurological disease during the acute infectious period [1]. Reported neurologic phenomenon include anosmia, ageusia, seizures, meningoencephalitis, cerebrovascular disease, Guillain-Barré syndrome, postviral polyneuropathies, encephalitis, and acute disseminated encephalomyelitis (ADEM) particularly with hemorrhage (also termed acute necrotizing encephalitis) [2]. Roughly 34% of children with SARS-CoV-2 related multisystem inflammatory syndrome in children have identified neurological manifestations, although these have generally been less severe phenotypes than observed in adults [3]. Although encephalitis has been reported, this was in the setting of acute infection [4], and thus far no postinfectious neurologic phenomenon have been reported.

In children, MOG antibodies are associated with a variety of postinfectious acquired demyelinating disorders, demonstrating a strong predilection for children. MOG antibodies have been identified over the last decade to be intimately linked with acquired demyelinating diseases with a strong predilection for striking in the pediatric age spectrum. Reported neurologic phenomenon associated with MOG antibodies include ADEM, optic neuritis, transverse myelitis, neuromyelitis optica, and autoimmune encephalitis. Although the exact etiology to MOG spectrum disorders is unknown, postinfectious molecular mimicry and epitope spreading are hypothesized. MOG antibody associated encephalomyelitis has been reported in 67% with infectious prodrome and have been related to postinfectious conditions including herpes simplex virus (HSV), Epstein-Barr virus (EBV), others [5]. Armangue et al [6]. have shown in their prospective study that HSV encephalitis can trigger autoimmune encephalitis in 27% of patients. SARS-CoV-2 being neurotropic might play similar role.

To date, there have been no associated cases of MOG spectrum disorders in children associated with either acute or postinfectious infection with SARS-CoV-2. Here we present a case of a 7-year-old female with a prior asymptomatic infection with SARS-CoV-2 who subsequently developed encephalopathy and status epilepticus in association with MOG antibody positivity. The presence of SARS-CoV-2 could be a coincidence, but a prior study has shown higher rates of nonencephalitic past HSV-1 infection significantly more in N-methyl-D-aspartate receptor encephalitis suggesting meaningful association between infection and the antibody mediated encephalitis [7]. The phenotype in our case is characteristic of pediatric onset MOG spectrum disorders in that seizures, encephalopathy, and immunotherapy responsiveness are all reported. Although the patient’s radiographic findings are inconsistent with ADEM the clinical presentation of encephalopathy and seizure does match this disorder well, as does the presence of MOG antibodies. For this reason, the authors feel strongly that the patients presentation is associated with the presence of SARS-CoV-2 antibodies in spite of the patient having no occult respiratory illness reported by the family.

The exact mechanism is obscure whereas SARS-CoV-2 had been associated with autoimmune encephalitis in pediatric [8], adults and the proposed mechanism of MOG antibodies presence is likely heterogeneous including molecular mimicry with identification of self antigens as foreign in the presence of similarity of epitopes, or initial infection leading to dispersion of central nervous system antigens to periphery with development of autoantibodies to myelin protein. Although restricted diffusion was present in our case, the radiographic findings are inconsistent with cerebrovascular disease or vasculopathy although the latter has been reported in persons with MOG antibodies and SARS-CoV-2 infection [9].

While singular cases are difficult to generalize to the greater population, there are 2 important factors of relevance to treating neurologists. Firstly, the potential link between prior SARS-CoV-2 infection and the subsequent development of neuroinflammatory disease is of importance given the high rates of infection around the globe. Although prevention of SARS-CoV-2 is of primary importance, understanding that MOG antibody spectrum disorders can occur in the postinfectious period is of importance. Further, amongst neurologists and pediatricians evaluating patients with new onset seizure activity or ADEM-like presentations, ascertainment of SARS-CoV-2 antibody status may be of importance from both a treatment and prognostication standpoint as postinfectious neuroinflammation tends to be monophasic [10]. This is of greater importance in pediatric patients as there may be no occult respiratory phenomenon with initial infection.