Neurologic and Psychiatric Morbidity Linked to Severe COVID-19 Infections

Maxime Taquet, PhD

Since the beginning of the COVID-19 pandemic there has been a fear of long-term neurological and psychiatric sequalae. However, this theory previously has lacked the data needed to properly assess how COVID-19 impacts brain health.

A team, led by Maxime Taquet, PhD, Department of Psychiatry, University of Oxford, gave estimates on incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis.

Obtaining the Data

In the retrospective cohort study and time-to-event analysis, the researchers used data obtained from the TriNetX electronic health records involving over 81 million patients.

The primary cohort involved 236,379 COVID-19 patients and the matched control cohort included patients diagnosed with influenza. The other matched control cohort included patients diagnosed with any respiratory tract infection including influenza in the same period. All 3 cohorts included patients older than 10 who had an index event on or after Jan. 20, 2020 and were still alive as of Dec. 13, 2020.

The researchers estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months following a COVID-19 diagnosis, including intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root, and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders (grouped and separately); substance use disorder; and insomnia.

The Comparison

They then used a Cox model to compare incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections.

They also investigated how these estimates were impacted by COVID-19 severity, as proxied by hospitalization, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders and assessed the robustness of the differences in outcomes between cohorts by repeating the analysis in different scenarios.

“To provide benchmarking for the incidence and risk of neurological and psychiatric sequelae, we compared our primary cohort with four cohorts of patients diagnosed in the same period with additional index events: skin infection, urolithiasis, fracture of a large bone, and pulmonary embolism,” the authors wrote.

Results

The estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33.6% (95% CI, 33.17-34.07) of the COVID-19 patients, with 12.84% (95% CI, 12.36-13.33) receiving their first such diagnosis.

For the patients who were admitted to the ITU,. The estimated incidence of a diagnosis was 46.42% (95% CI, 44.78-48.09). The estimated incidence for a first diagnosis was 25.7% (95% CI, 23.50-28.25).

For the individual diagnoses of the study outcomes, the entire COVID-19 cohort had estimated incidences of 0.56% (95% CI, 0.50–0.63) for intracranial hemorrhage, 2.10% (95% CI, 1.97–2.23) for ischemic stroke, 0.11% (95% CI, 0.08–0.14) for parkinsonism, 0.67% (95% CI, 0.59–0.75) for dementia, 17.39% (95% CI, 17.04–17.74) for anxiety disorder, and 1.40% (95% CI, 1.30–1.51) for psychotic disorder, among others.

For the patients in the group with ITU admissions, estimated incidences were 2.66% (95% CI, 2.24–3.16) for intracranial hemorrhage, 6.92% (95% CI, 6.17–7.76) for ischemic stroke, 0.26% (95% CI, 0.15–0.45) for parkinsonism, 1.74% (95% CI, 1.31–2.30) for dementia, 19.15% (95% CI, 17.90–20.48) for anxiety disorder, and 2.77% (95% CI, 2.31–3.33) for psychotic disorder.

The majority of diagnostic categories were common in COVID-19 patients than it was in patients with influenza (HR, 1.44; 95% CI, 1.40–1.47, for any diagnosis; HR, 1.78; 95% CI, 1.68–1.89, for any first diagnosis) and those who had other respiratory tract infections (HR, 1.16; 95% CI, 1.14–1.17, for any diagnosis; HR, 1.32; 95% CI, 1.27–1.36, for any first diagnosis).

The hazard ratios were higher in patients who had more severe COVID-19 cases and the results were robust to various sensitivity analyses and benchmarking against the 4 additional index health events.

“Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection,” the authors wrote. “Risks were greatest in, but not limited to, patients who had severe COVID-19. This information could help in service planning and identification of research priorities. Complementary study designs, including prospective cohorts, are needed to corroborate and explain these findings.”

The study, “6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records,” was published online in The Lancet Psychiatry.