Neurologic disorders were detected prospectively in one in seven hospitalized COVID-19 patients, a New York City study showed.
Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset, reported Jennifer Frontera, MD, of NYU Langone Health, and co-authors.
As shown in the study online in , hospitalized COVID-19 patients with new neurologic disorders had an adjusted 38% increased risk of in-hospital mortality and a 28% reduced likelihood of being discharged home compared with those without neurologic disorders.
This is the first prospective study of neurologic disorders in hospitalized patients with confirmed COVID-19 in the U.S. Unlike other research -- which has reported prevalence of neurologic findings in hospitalized COVID-19 patients as high as 82% -- the study did not include non-specific neurologic symptoms like myalgia, headache, or dizziness, but included only diagnoses made by a neurologist.
"Ours is the first study where we get a real indication of incidence of events," Frontera said.
As in other studies, encephalopathy was prominent: the most common new-onset neurologic diagnoses among hospitalized COVID-19 patients were toxic/metabolic encephalopathy (6.8%), stroke (1.9%), seizure (1.6%), and hypoxic/ischemic injury (1.4%). Less than 1% developed movement disorder, 0.8% developed neuropathy, 0.5% myopathy, and 0.1% Guillain-Barré syndrome.
No patient had meningitis, encephalitis, myelopathy, or myelitis related to SARS-CoV-2 infection. In a sample of 18 cerebrospinal fluid specimens, all 18 were reverse transcription polymerase chain reaction negative for SARS-CoV-2.
The complications that emerged most frequently also are common among critically ill patients, especially those with acute respiratory distress syndrome, sepsis, hypoxia, and acute renal failure, Frontera noted.
"There's a lot of hypoxic brain injury happening," she told . "The vast majority of what we saw really was just the consequence of being critically ill and profoundly hypoxic for prolonged periods of time."
An important finding is that the study showed no cases of brain or nerve inflammation like encephalitis, meningitis, or myelitis, Frontera pointed out.
"That doesn't mean it doesn't happen, but this is a very large data set so if it does happen, it's incredibly rare," she said. "The real question has always been how neuroinvasive is this virus? Is it like SARS? And to me, the jury's still out."
The study looked at patients hospitalized with laboratory-confirmed SARS-CoV-2 infection from March 10 to May 20, a timeframe that included a surge in COVID-19 cases in New York City. Patients were admitted to one of four NYU Langone hospitals in Manhattan, Brooklyn, or Mineola, New York.
The median age of COVID-19 patients with new neurologic disorders was 71, and 66% were men; median age of those without neurologic disorders was 63, and 57% were men. COVID-19 patients with neurologic disorders more often were white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment () scores (all P<0.05).
All neurologic diagnoses were made by neurologists using guidelines established by the Global Consortium Study of Neurological Dysfunction in COVID-19 ), excluding recrudescence of old neurologic deficits. Diagnoses were categorized as toxic/metabolic encephalopathy, stroke, hypoxic/ischemic brain injury, seizure, neuropathy (including Guillain-Barré syndrome), myopathy, movement disorder, encephalitis, meningitis, myelitis, or myelopathy.
Toxic/metabolic encephalopathy diagnoses included patients with temporary, reversible changes in mental status, and excluded patients in whom sedatives, other drugs, or hypotension could explain the presentation. Etiologies included electrolyte abnormalities, uremia, liver failure, acid/base disorders, sepsis/active infection, hypertension, hypoxia, or hypercarbia.
Of patients with neurologic disorders, 43% developed neurologic symptoms and traditional COVID-19 symptoms such as cough, shortness of breath, or fever at approximately the same time. Just over half (54%) developed neurologic symptoms after COVID-19 symptoms, in a median of 12 days.
After the researchers adjusted for age, sex, SOFA scores, intubation, past history, medical complications, medications, and comfort care status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (HR 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001).
The study had several limitations, Frontera and co-authors noted. Patients with limited examinations due to sedation or paralysis may have had undetected neurologic disorders, and neurologists may not have been consulted on patients with mild neurologic symptoms. In addition, illness severity may have prevented some patients from providing a detailed history of neurologic symptoms.
Disclosures
Funding support for the study was provided by the National Institutes of Health (NIH) and NYU Langone.
Frontera disclosed university and NIH grants; no other relationships were reported.
Primary Source
Neurology
Frontera J, et al "A Prospective Study of Neurologic Disorders in Hospitalized COVID-19 Patients in New York City" Neurology 2020; DOI: 10.1212/WNL.0000000000010979.