Risk was greater than reported in influenza patients

Roughly a third of Covid-19 patients had a neurologic or psychiatric diagnosis in the six months following treatment in one of the first large retrospective studies to estimate the long-term risks of these disorders following SARS-CoV-2 infection.

Researchers examined data from a health records network with over 81 million members to identify patients treated for Covid-19 and compare the incidence of a neuropsychiatric diagnosis within six months to patients treated for other respiratory tract infections, including influenza, during the same period.

They found that 33% of Covid-19 patients had a neurological or psychiatric diagnosis during the six months after Covid-19 diagnosis, including close to 13% who had not previously had such diagnoses. Compared to patients treated for influenza, those treated for Covid-19 were 44% more likely to be diagnosed with a neuropsychiatric disorder and 78% more likely to receive a first neurologic or psychiatric diagnosis.

Compared to patients with Covid-19 who were not hospitalized, hospitalized patients who developed delirium had a more than five-fold increased risk for a first diagnosis of psychotic disorder during the six months after treatment (HR, 5.62, 95% CI, 2.93-10.77).

Writing in The Lancet Psychiatry, researcher Paul J. Harrison, FRCPsych, of the University of Oxford, United Kingdom, and colleagues, noted that the findings provide “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.”

The researchers evaluated data from the TriNetX Analytics Network, which includes health records from 62 healthcare organizations primarily located within the United States with more than 81 million patients.

The primary cohort was made up of patients with a confirmed diagnosis of Covid-19 after mid-January 2020 who were still alive by mid-December, matched 1:1 with a patient diagnosed with influenza during the same period. A second matched cohort included patients diagnosed with any respiratory disease, excluding Covid-19 but including influenza, during the period.

Researchers evaluated the incidence of 14 neuropsychiatric disorders in the six months following Covid-19 diagnosis, and Cox modeling was used to compare incidences with influenza patients or patients with other respiratory tract infections.

“We investigated how these estimates were affected by Covid-19 severity, as proxied by hospitalization, intensive therapy unit (ITU) admission, and encephalopathy (delirium and related disorders),” the researchers wrote.

They repeated the analysis in different scenarios to test the robustness of the differences between cohorts.

Among a total of 236,379 patients diagnosed with Covid-19, the estimated incidence of a neurological or psychiatric diagnosis in the six months following diagnosis was 33.62% (95% CI, 33.17–34.07), with 12.84% (95% CI, 12.36–13.33) receiving their first such diagnosis.

The analysis also revealed:

  • Among Covid-19 patients requiring treatment in intensive care, the estimated incidence of a neurological or psychiatric diagnosis was 46.42% (95% CI, 44.78-48.09).
  • Covid-19 patients 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.
  • Among Covid-19 patients who required treatment in intensive care the 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.
  • Diagnosis of neurological and psychiatric disorders was 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, 95% CI, 1.68-1.89, for any first diagnosis) and those who had other respiratory tract infections (1.16, 05% CI, 1.14-1.17, for any diagnosis; 1.32, 95% CI, 1.27-1.36, for any first diagnosis).
Having severe Covid-19 requiring intensive care treatment was associated with a roughly three-fold greater risk (HR, 2.87; 95% CI, 2.45-3.35) for a first diagnosis of a neurological and/or psychiatric disorder.
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In commentary published with the study, Jonathan P. Rogers, BChir, MRCP, MRCPsych, and Anthony S. David, FMedSci, of the University College London, highlighted the clinical implications of several new observations in the analysis.

“A relationship between Covid-19 and ischemic stroke has been well described, though Covid-19 seems to be a stronger risk factor for intracranial hemorrhage, albeit a rarer event, than for ischemic stroke,” they wrote. “Data on a relationship with dementia have been sparse, and the high hazard ratio (1.88, 95% CI, 1.27-2.77) for dementia in patients with Covid-19 compared with influenza is concerning, although this could indicate better case ascertainment. Fortunately, initial alarming reports of Guillain-Barré syndrome in relation to Covid-19 do not seem to have been borne out by this or other large-scale epidemiological studies.”

Rogers and David noted that similar concerns about “a wave of encephalitis lethargica, analogous to that sometimes linked to the 1918 influenza pandemic, were not supported by the rather equivocal relationship between Covid-19 infection and Parkinsonism.”

They further noted that the observed high risk for psychotic disorder following hospitalization for Covid-19 that included delirium is concerning, “even if the underlying mechanism turns out to be indirect.”

“The findings… could be consistent with the psychoses being triggered by external causes, but, more likely, they could be exacerbations of pre-existing conditions unknown to the healthcare provider,” they wrote. “Additionally, an association between psychosis (and dementia) and encephalopathy could be due to reverse causality.”

  1. One-in-three Covid-19 patients had a neurologic or psychiatric diagnosis in the six months following treatment in one of the first large retrospective studies to estimate the long-term risks of these disorders following SARS-CoV-2 infection.

  2. Compared to patients treated for influenza, those treated for Covid-19 were 44% more likely to be diagnosed with a neurological or psychiatric disorder and 78% more likely to receive a first neurologic or psychiatric diagnosis.

Salynn Boyles, Contributing Writer, BreakingMED™

This research was funded by the National Institute for Health Research (NIHR) Oxford Health Biomedical Research Center.

Researcher Sierra Luciano reported being an employee of TriNetX. Commentary writer Rogers reported holding an advisory meeting with representatives from Promentis Pharmaceuticals regarding drug development. No other declarations were made.

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