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Hospitalized COVID-19 patients with acute neurologic syndromes and signs had a much higher risk of death, the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) study showed.

Mortality was nearly six times higher in hospitalized COVID-19 patients with clinically verified neurologic manifestations than in hospitalized COVID-19 patients with or without neurologic features (OR 5.99, 95% CI 4.33-8.28, P<0.001), reported Sherry Chou, MD, of the University of Pittsburgh at the American Academy of Neurology (AAN) virtual meeting in a special session. The venue provided the first look at data from , a observational study endorsed by the Neurocritical Care Society.

Acute encephalopathy including delirium (50%), coma (17%), and strokes (3.1%) were the most prevalent clinically verified acute neurologic manifestations in the study. Encephalopathy specifically was tied to a 5.5-fold increase in death (95% CI 4.01-7.57, P<0.001).

The presentation included data about 3,055 consecutive adult COVID-19 patients hospitalized in 13 countries from March 1 to Sept. 30, 2020. In addition, 475 patients were included in a COVID-neurological cohort, which required a patient to be identified with a neurological condition or abnormality as entry criteria.

Men made up 57% of the total sample. Overall, 48% of participants were white and 23% were Black. Mean age was 60 for all hospitalized COVID patients and 63 for those in the COVID-neurological cohort.

Acute hospital mortality was 14% in the general COVID group and 25% in the COVID-neurological group. Researchers grouped neurologic manifestations into two categories: self-reported symptoms, or clinically verified neurologic symptoms and signs.

In the general COVID group, 2,439 people (80%) had neurologic symptoms throughout their course, including clinically verified acute encephalopathy (n=1,541; 50%) or coma (n=509; 17%) and self-reported headache (n=1,165; 38%) or anosmia/ageusia (n=840; 28%). Prevalence of verified neurologic symptoms, especially encephalopathy, increased with age; prevalence of self-reported symptoms like headache was higher in younger patients.

In unadjusted analysis, having a pre-existing neurologic disorder was associated with higher mortality (OR 1.68, 95% CI 1.34-2.11, P<0.001). In adjusted analysis, clinically verified neurologic manifestations increased mortality six-fold, driven by acute encephalopathy (OR 5.51, 95% CI 4.01-7.57, P<0.001) and coma (OR 7.70, 95% CI 5.65-10.5, P<0.001).

"Interestingly, if you look at headache and anosmia, these self-reported symptoms are actually inversely associated with death," Chou pointed out. "We do not believe that our data suggests that there is a biological protective effect where headache prevents one from dying from COVID," she said. "But the fact that someone is well enough to report the symptoms of headache and anosmia may drive this association that we see in this population."

In adjusted analysis, the most important predictor for developing new neurologic signs and symptoms was having a pre-existing neurologic disorder (OR 2.23, 95% CI 1.80-2.75, P<0.001), followed by male sex and older age.

The GCS-NeuroCOVID study is ongoing, and future work includes validating these findings in a larger cohort, Chou said. "We still have many critical knowledge gaps, but one of the biggest questions we have now is what are the subacute and long-term outcomes of this cohort of patients who had acute neurological dysfunction with COVID-19," she noted. One of the next steps is to follow survivors and "see how they fare in the rest of their care."

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