We read with interest the article by Burr et al. on NMDA-receptor (NMDAR) encephalitis associated with COVID-19 infection.1 Although anti-NMDAR encephalitis has been associated with COVID-19 in adults, this is the first report in a child.2 The initial evidence suggested that COVID-19 infections are often asymptomatic or mildly symptomatic in children, but identification of para/postinfectious immune-mediated neurological complications associated with COVID-19 is important. Several neurological presentations have been documented in children and adults with COVID-19 infections. Parainfectious complications include autoimmune encephalitis, autoimmune epilepsy, central nervous system demyelination, Guillain-Barre syndrome, and acute necrotizing encephalopathy.4 With inflammation playing a major role, these conditions probably share a final common pathway; this also explains the benefit of immunotherapy in these conditions. Because these parainfectious neurological syndromes have an infectious trigger (herpes, dengue, etc.), COVID-19 testing may be appropriate in patients with these disorders.3 Asymptomatic or mildly symptomatic children with COVID-19 may not be identified during the acute phase and may present later with parainfectious complications, etc. We may be missing COVID-19 infections in children with isolated neurological complications such as Guillain-Barre syndrome and demyelination. Thus, we emphasize the need to consider COVID-19 testing (reverse transcriptase polymerase chain reaction and antibodies IgM and IgG) along with analysis of syndrome-based antibodies like anti-NMDAR and myelin oligodendrocyte glycoprotein antibodies in the evaluation of parainfectious neurological syndromes. This approach will not only establish the etiology but could also provide important epidemiologic data. With growing evidence of the role of viral infections in autoimmune neurological disorders, it is plausible that many parainfectious conditions are under-recognized in children.5
To treat intractable cases of autoimmune encephalitis, the need for novel immunotherapy that penetrates the blood-brain barrier (BBB) is increasing. Tofacitinib is a Janus kinase (JAK) inhibitor used to treat refractory immune-mediated diseases that effectively penetrates the BBB.