6-month neurological and psychiatric findings in 236379 COVID-19 survivors: a retrospective cohort study using electronic health records

Background

Neurological and psychiatric effects of COVID-19 have been reported, but more data are needed to adequately assess the effects of COVID-19 on brain health. We aimed to provide robust estimates of incidence rates and relative risks of neurological and psychiatric diagnoses in patients in the 6 months following a COVID-19 diagnosis.

Methods

For this retrospective cohort study and time for event analysis, we used data obtained from TriNetX electronic health record network (with over 81 million patients). Our primary cohort included patients who had a COVID-19 diagnosis; one matched control cohort included patients diagnosed with influenza, and the other matched control cohort included patients diagnosed with any respiratory infection including influenza during the same period. Patients with a diagnosis of COVID-1

9 or a positive test for SARS-CoV-2 were excluded from the control groups. All cohorts included patients older than 10 years who had an index event on 20 January 2020 or later and who were still alive on 13 December 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome nerve, nerve root and plexus disorders myoneural junction and muscle disease encephalitis; dementia psychotic, mood swings and anxiety disorders (grouped and separate); substance use disorder and insomnia. Using a Cox model, we compared occurrences with those in propensity-score-matched cohorts of patients with influenza or other respiratory infections. We examined how these estimates were affected by the COVID-19 severity as approached by hospitalization, intensive care (ITU), hospitalization, and encephalopathy (delirium and related disorders). We assessed the robustness of the differences in results between cohorts by repeating the analysis in different scenarios. To provide benchmarking for the incidence and risk of neurological and psychiatric consequences, 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.

Results

Among 236,379 patients diagnosed with COVID-19, the estimated incidence of a neurological or psychiatric diagnosis in the following 6 months was 33 · 62% (95% CI 33 · 17–34 · 07) with 12 · 84% (12 · 36– 13 · 33) receive their first such diagnosis. For patients admitted to an ITU, the estimated incidence of a diagnosis was 46 · 42% (44 · 78–48 · 09) and for a first diagnosis was 25 – 79% (23 · 50-28 · 25) . Regarding individual diagnoses of the study results, the entire COVID-19 cohort had an estimated incidence of 0 · 56% (0 · 50–0 · 63) for intracranial haemorrhage, 2 · 10% (1 · 97-2 · 23) for ischemic stroke , 0 · 11% (0 · 08–0 · 14) for parkinsonism, 0 · 67% (0 · 59–0 · 75) for dementia, 17 · 39% (17 · 04–17 · 74) for anxiety disorder and 1 · 40% (1 · 30-1 · 51) for, among other things, psychotic disorder. In the group with ITU admission, estimated incidence was 2 · 66% (2 · 24–3 · 16) for intracranial haemorrhage, 6 · 92% (6 · 17–7 · 76) for ischemic stroke, 0 · 26% (0 · 15–0 · 45) for parkinsonism, 1 · 74% (1 · 31–2 · 30) for dementia, 19 · 15% (17 · 90–20 · 48) for anxiety disorder and 2 · 77% (2 · 31– 3 · 33) for psychotic disorder. Most diagnostic categories were more common in patients with COVID-19 than in those with influenza (hazard ratio [HR] 1 · 44, 95% CI 1 · 40–1 · 47 for any diagnosis; 1 · 78, 1 · 68–1 · 89, for any initial diagnosis) and those who had other respiratory infections (1 · 16, 1 · 14–1 · 17, for any diagnosis; 1 · 32, 1 · 27–1 · 36, for any initial diagnosis). As with the incidence, HRs were higher in patients who had more severe COVID-19 (eg those admitted to ITU compared to those who were not: 1 · 58, 1 · 50-1 · 67, for any diagnosis ; 2 · 87, 2 · 45–3 · 35 for any initial diagnosis). The results were robust to different sensitivity analyzes and benchmarking compared to the four additional index health events.

Interpretation

Our study provides evidence of significant neurological and psychiatric morbidity in the 6 months following COVID-19 infection. The risk was greatest in, but not limited to, patients who had severe COVID-19. This information can help with service planning and identification of research priorities. Complementary study designs, including potential cohorts, are needed to confirm and explain these findings.

Financing

National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center.