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Six months after COVID-19 infection, the psychiatric and neurological outcomes are frightening until you look at the y-axis. How much risk does this virus pose to your and your patients’ brains?
Hi! Jim Phelps here for the Psychopharmacology Institute. In a new Lancet Psychiatry article, Dr. Maxime Taquet and colleagues examined the medical records of 236,000 patients and looked at the rates of a bunch of very bad events—ischemic stroke, myoneural junction or muscle disease, dementia, mood or anxiety disorders, psychosis, even insomnia —and they compared rates for those infected with COVID-19 vs rates in patients infected by the influenza virus or other respiratory tract infections. Granted, this all sounds rather frightening before we even start, so let’s begin with the good news.
Almost all the bad outcomes that the authors examined—stroke, muscle disease, psychiatric illness —were more common in patients with COVID-19 than with other respiratory tract infections, but the absolute rates were relatively low. You can see this in the authors’ graphs of rates for the bad outcomes just by looking at the y-axis. For example, COVID was clearly more likely to cause a first intracranial hemorrhage than other respiratory tract infections. The curves clearly separate, but the y-axis scale of rates goes from 0.2 to 0.8. We’re talking about a less than 1% risk for intracranial hemorrhage.
For myoneural junction or muscle disease, there was a big separation vs other respiratory tract infections, but the y-axis shows rates of 0.1 vs 0.6. So, the bottom line is, yes, COVID is worse than other respiratory tract infections for multiple negative outcomes, but the absolute frequency of those bad outcomes is still very small.
For an example closer to home, a first episode of psychosis was 80% more likely to occur after COVID infection than after other respiratory tract infections, but first episode of psychosis occurred in only 0.42% of all patients with COVID.
What were the other outcomes clearly associated with COVID vs other respiratory tract infections? Stroke, myoneural junction or muscle disease, and dementia, all with low incidence rates. But a couple of diagnoses had absolute rates that were not low—new-onset mood and anxiety disorders, affecting 8% and 7% of COVID patients, respectively.
Finally, there was an epidemic of parkinsonism that followed the 1918 flu epidemic. Does COVID pose this risk? The authors conclude, “Our data provide some support for this possibility, although the incidence was low and not all hazard ratios were significant.” They conclude that parkinsonism might be a delayed outcome, and that a clearer signal might emerge with longer follow up.
More severe infections with COVID, especially those requiring intensive care, were more associated with neurological and psychiatric diagnoses, with a kind of dose–response effect. Perhaps that’s not surprising. The authors noted that potential mechanisms for this association include viral invasion of the central nervous system, hypercoagulable states, and neural effects of the immune response.
For more on all these, check out Figure 1, which has striking curves. But, again, that’s in part due to the scale on the y-axis—a good reminder to be careful when you see an impressive result.
Abstract
6-Month Neurological and Psychiatric Outcomes in 236 379 Survivors of COVID-19: A Retrospective Cohort Study Using Electronic Health Records
Maxime Taquet, John R Geddes, Masud Husain, Sierra Luciano, Paul J Harrison
Background: Neurological and psychiatric sequelae 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-to-event analysis, we used data obtained from the TriNetX electronic health records network (with over 81 million patients). Our primary cohort comprised 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 tract infection including influenza in the same period. Patients with a diagnosis of COVID-19 or a positive test for SARS-CoV-2 were excluded from the control cohorts. All cohorts included patients older than 10 years who had an index event on or after Jan 20, 2020, and who were still alive on Dec 13, 2020. We estimated the incidence of 14 neurological and psychiatric outcomes in the 6 months after a confirmed diagnosis of COVID-19: intracranial haemorrhage; ischaemic 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. Using a Cox model, we compared incidences with those in propensity score-matched cohorts of patients with influenza or other respiratory tract infections. We investigated how these estimates were affected by COVID-19 severity, as proxied by hospitalisation, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders). We 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.
Findings: 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) receiving their first such diagnosis. For patients who had been 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 outcomes, the whole COVID-19 cohort had estimated incidences of 0·56% (0·50-0·63) for intracranial haemorrhage, 2·10% (1·97-2·23) for ischaemic 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 psychotic disorder, among others. In the group with ITU admission, estimated incidences were 2·66% (2·24-3·16) for intracranial haemorrhage, 6·92% (6·17-7·76) for ischaemic 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 who had COVID-19 than in those who had influenza (hazard ratio [HR] 1·44, 95% CI 1·40-1·47, for any diagnosis; 1·78, 1·68-1·89, for any first diagnosis) and those who had other respiratory tract infections (1·16, 1·14-1·17, for any diagnosis; 1·32, 1·27-1·36, for any first diagnosis). As with incidences, HRs were higher in patients who had more severe COVID-19 (eg, those admitted to ITU compared with those who were not: 1·58, 1·50-1·67, for any diagnosis; 2·87, 2·45-3·35, for any first diagnosis). Results were robust to various sensitivity analyses and benchmarking against the four additional index health events.
Interpretation: Our study provides evidence for substantial neurological and psychiatric morbidity in the 6 months after COVID-19 infection. 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.
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Reference
Taquet, M., Geddes, J. R., Husain, M., Luciano, S., & Harrison, P. J. (2021). 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: A retrospective cohort study using electronic health records. The Lancet Psychiatry, 8(5), 416–427.
