Poor 90-Day Outcomes With Acute Encephalopathy, Coma in Severe COVID-19

There was a low prevalence of acute encephalopathy among patients with COVID-19 admitted to an ICU, but more than half with the condition had poor outcomes.

Among critically ill patients with COVID-19, the development of acute encephalopathy, albeit rare, is associated with poor 90-day outcomes, according to findings from an observational study published in the journal Neurology.

In individuals with severe SARS-CoV-2 infection, the alteration of consciousness that presents as acute encephalopathy can vary from delirium to coma, which frequently evolves quickly over a matter of hours to several days. Elucidation of the “epidemiology and outcomes of adults with severe COVID-19 and acute encephalopathy may help inform clinicians, patients, and their families when goals of care are discussed.” In an effort to address these gaps in knowledge, researchers sought to conduct an international prospective study (ClinicalTrials.gov Identifier: NCT04320472).

The primary study objective was to describe the outcomes, characteristics, and prevalence of acute encephalopathy in adult patients with a severe COVID-19 infection who required management in a hospital intensive care unit (ICU).

The secondary study objective was to identify factors that were related to a poor 90-day outcome. The researchers prospectively obtained data from ICU-managed adults at 31 university or university-affiliated ICUs in Brazil, Colombia, France, Mexico, Spain, and the United States who were admitted between March 2020 and September 2020.

Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology.

Acute encephalopathy was defined as “subsyndromal delirium or delirium, or as a comatose state in case of severely decreased level of consciousness.”

The presence of a comatose state was defined as a Glasgow Coma Scale (GCS) score of <9. There were some individuals who might have experienced subdelirium or delirium that progressed to coma. Functional outcomes at 90 days were evaluated with use of the Glasgow Outcome Scale-Extended score (GOS-E scale), which ranged from 1 to 8. A rating of 8 was indicative of the best score, with “good” scores in the 5 to 8 range, and “poor” scores in the 1 to 4 range, which represented death, a vegetative state, or severe disability.

Among a total of 4,060 adults with a SARS-Cov-2 infection admitted to a participating ICU over the 6-month study period, 374 experienced acute encephalopathy prior to or at ICU admission — 154 in France/Spain, 111 in the United States, and 109 in Brazil/Colombia/Mexico. The median patient age was 68 years (range, 58-74 years). Overall, 63.9% of participants were men and 16.6% of them had a history of neurologic disease.

There were 29 patients lost to follow-up, thus leaving 345 individuals in the final cohort. In all, 57.7% (199 of 345) of the participants experienced a poor outcome at the 90-day follow-up, based on the GOS-E.

Per multivariable analysis, the following factors were independently linked to a higher likelihood of a poor outcome at 90 days:

  • Age >70 years: odds ratio (OR), 4.01; 95% CI, 2.25-7.15
  • Presumed fatal comorbidity: OR, 3.98; 95% CI, 1.68-9.44
  • GSC score of <9 prior to or at ICU admission: OR, 2.20; 95% CI, 1.22-3.98
  • Need for vasopressor/inotrope support during ICU stay: OR, 3.91; 95% CI, 1.97-7.76
  • Need for renal replacement therapy during ICU stay: OR, 2.31; 95% CI, 1.21-4.50
  • Central nervous system ischemic or hemorrhagic complications as the acute encephalopathy etiology: OR, 3.22; 95% CI, 1.41-7.82

Posterior reversible encephalopathy syndrome, reversible cerebral vasoconstriction syndrome, and status epilepticus all were associated with a lower likelihood of a poor 90-day outcome (OR, 0.15; 95% CI, 0.03-0.83).

A study limitation that warrants mention includes the potential underreporting of certain neurologic complications, including strokes and seizures, due to the lack of requiring participating centers to obtain lumbar punctures, imaging, or electroencephalograms.

“Determinants of poor 90-day outcome were dominated by older age, comorbidities, degree of impairment of consciousness before/at ICU admission, association with other organ failures, and acute encephalopathy etiology,” the researchers concluded.


Legriel S, Badenes R, Engrand N, et al. Outcomes in COVID-19 patients with acute encephalopathy and coma: an international prospective study. Neurology. Published online April 11, 2023. doi:10.1212/WNL.0000000000207263