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More than 80% of hospitalized COVID-19 patients had neurologic symptoms during their disease course, a retrospective Chicago-area study showed.

Neurologic manifestations were present at COVID-19 onset in 42.2% of 509 consecutive hospitalized COVID-19 patients, at hospitalization in 62.7%, and at anytime during the disease course in 82.3%, reported Igor Koralnik, MD, of Northwestern Medicine in Chicago, and colleagues in the .

Myalgia (44.8%), headache (37.7%), encephalopathy (31.8%), and dizziness (29.7%) were the most frequent neurologic manifestations, followed by dysgeusia (15.9%) and anosmia (11.4%).

Patients presenting with neurologic symptoms were younger than those who didn't have symptoms. Most patients with neurologic manifestations had a favorable functional outcome at discharge, but encephalopathy -- which affected nearly one in three patients -- was associated with increased morbidity and mortality, independent of respiratory disease severity.

"This is the first study in the U.S. of the prevalence of neuro manifestations in a large population of hospitalized patients," Koralnik told 番茄社区app. Only two other papers describing the prevalence of neurological manifestations in hospitalized COVID-19 patients have been published: one based in China, the other in Spain.

Neurological complications of COVID-19 are frequent and in many cases long-lasting, but have not yet received much attention, noted Avindra Nath, MD, senior investigator of nervous systems infections at the NIH National Institute of Neurological Disorders and Stroke, who wasn't involved with the study.

"While it is not unexpected that the sickest patients would have the most neurological complications, it is surprising that these manifestations occur more commonly in younger individuals and is independent of the severity of respiratory involvement," Nath told 番茄社区app.

The study's retrospective nature may mean the frequency of neurologic manifestations is underreported, he pointed out.

In their study, Koralnik and colleagues retrospectively analyzed the first 509 consecutive patients admitted with COVID‐19 to the Northwestern Medicine Healthcare system between March 5 and April 6. The Northwestern Medicine system consists of one academic medical center and nine other hospitals in the Chicago area.

COVID‐19 diagnosis was confirmed by SARS‐CoV‐2 reverse transcription‐polymerase chain reaction (RT‐PCR) assay. Encephalopathy was identified by report of altered mental status or depressed level of consciousness, physician-documented diagnosis of encephalopathy or delirium encephalopathy syndrome, or positive evaluation.

Functional outcome at hospital discharge was based on modified Rankin Scale (), a six-point disability scale in which scores of 0-2 mean a patient can look after his or her own affairs without assistance and 6 represents death.

Patients were age 58.5 on average and 55.2% were men; 134 patients (26.3%) had severe COVID‐19 requiring mechanical ventilation. In total, 419 of the 509 patients had neurologic manifestations at any time during the disease course. Independent risk factors for developing any neurologic manifestation were severe COVID‐19 (OR 4.02, 95% CI 2.04–8.89, P<0.001) and younger age (OR 0.982, 95% CI 0.968–0.996, P=0.014).

Strokes, movement disorders, motor and sensory deficits, ataxia, and seizures were uncommon (0.2 to 1.4% of patients each). Overall, 71.1% of hospitalized COVID-19 patients with neurologic symptoms were discharged with an mRS score of 0-2.

Hospitalized COVID-19 patients with encephalopathy were older than those without (66 vs 55 years, P<0.001), had a shorter time from COVID onset to hospitalization (6 vs 7 days, P=0.014), were more likely to be male, and to have a history of any neurological disorder, cancer, cerebrovascular disease, chronic kidney disease, diabetes, dyslipidemia, heart failure, hypertension, and smoking in assessments without multivariate adjustment.

"Triggers were likely multifactorial, including systemic disease -- multi-organ failure, coagulopathy, inflammation -- or direct infection of the brain by the virus, or post-infectious autoimmune mechanisms," Koralnik said.

Patients with encephalopathy had a median hospital stay of 17 days, while those without encephalopathy stayed a median of 5 days. At hospital discharge, 32.1% of patients with encephalopathy had an mRS score of 0-2, compared with 89.3% of those who did not develop encephalopathy.

Encephalopathy independently was associated with worse functional outcome (OR 0.22, 95% CI 0.11–0.42, P<0.001) and higher mortality within 30 days of hospitalization (21.7% vs 3.2%, P<0.001).

Overall, there was no meaningful difference in COVID-19 severity between patients at the academic medical center and ones at the nine other hospitals, but patients at the academic center had better functional outcomes and lower 30-day mortality.

"It's of concern that the outcome of patients was different in the various hospitals," Nath said. "The authors attribute this to differences in the quality of care provided. This means that hospitalized patients require high level of care which is not available in most places and points to an important vulnerability of our healthcare system."

The study had several limitations, including its retrospective nature and the fact that fewer than 6% of patients were evaluated by neurologists or neurosurgeons. With strict infection control precautions in place, access to brain CT or MRI was limited, the researchers said.

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