Six-month Neurological and Psychiatric Outcomes in 236,379 Survivors of COVID-19

Abstract

Background. Neurological and psychiatric sequelae of COVID-19 have been reported, but there are limited data on incidence rates and relative risks. Methods. Using retrospective cohort studies and time-to-event analysis, we estimated the incidence of ICD-10 diagnoses in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic stroke; Parkinsonism; Guillain-Barré syndrome; nerve/nerve root/plexus disorders; myoneural/muscle disease; encephalitis; dementia; mood, anxiety, and psychotic disorders; substance misuse; and insomnia. Data were obtained from the TriNetX electronic health records network (over 81 million patients). We compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory infections using a Cox model. We investigated the effect on incidence estimates of COVID-19 severity, as proxied by hospitalization and encephalopathy (including delirium and related disorders). Findings. 236,379 patients survived a confirmed diagnosis of COVID-19. Among them, the estimated incidence of neurological or psychiatric sequelae at 6 months was 33.6%, with 12.8% receiving their first such diagnosis. Most diagnostic categories were commoner after COVID19 than after influenza or other respiratory infections (hazard ratios from 1.21 to 5.28), including stroke, intracranial haemorrhage, dementia, and psychotic disorders. Findings were equivocal for Parkinsonism and Guillain-Barré syndrome. Amongst COVID-19 cases, incidences and hazard ratios for most disorders were higher in patients who had been hospitalized, and markedly so in those who had experienced encephalopathy. Results were robust to sensitivity analyses, including comparisons against an additional four index health events. Interpretation. The study provides evidence for substantial neurological and psychiatric morbidity following COVID-19 infection. Risks were greatest in, but not limited to, those who had severe COVID-19. The information can help in service planning and identification of research priorities.