SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction. Here we show that a particularly vulnerable population with neurologic manifestations of COVID-19 harbor an influx of inflammatory cytokines within the cerebrospinal fluid in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease models. Levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from the acute respiratory infection. These prolonged neurologic sequelae following a systemic cytokine release syndrome lead to long-term neurocognitive dysfunction with a wide range of phenotypes.

Sydenham’s chorea is a movement disorder seen in rheumatic fever with basal ganglia pathology. This disorder has been associated with an increased frequency of psychopathology in both the acute choreiform stage and later in life. We conducted a prospective study of 29 subjects with Sydenham’s chorea and 29 age- and sex-matched controls. The total number of psychiatric symptoms 10 years after the initial contact was much greater in the study group than in controls (p < 0.001). Similarly, schizophrenia was more common in the study group compared to controls (p < 0.01). Possible neuropathological associations and treatment are discussed.

Twenty-two patients with mania were evaluated for a variety of psychiatric phenomena. These items along with demographic data were used to predict relapse over a 36-month period in a multiple regression model. Formal thought disorder at the onset of illness was a strong predictor of relapse (F = 39, p < 0.001). The quality of the thought disorder was the most significant prognostic indicator. The predictive value of negative thought disorder was not enhanced by the addition of other symptomatic or demographic variables.