Neurological manifestations in people hospitalized with Covid-19 were prevalent and associated with increased mortality, a global multi-cohort study showed.
Across three groups of hospitalized Covid-19 patients, 82% had at least one new neurological sign or syndrome, according to Sherry Chou, MD, MSc, of University of Pittsburgh, and co-authors. Acute encephalopathy was the most common neurologic problem.
Covid patients with clinically diagnosed neurological symptoms were six times more likely to die during acute hospitalization than those without neurological manifestations (adjusted OR 5.99, 95% CI 4.33-8.28, P<0.001), they reported in JAMA Network Open.
“Taken together, these observations highlight the importance of neurological manifestations in Covid-19 and their potential impact on disease outcome,” Chou and colleagues wrote.
The study included consecutive patients in three cohorts who were hospitalized with Covid-19 across 15 sites worldwide between March 2020 and October 2020. Patients were combined from two data sources. The Global Consortium Study of Neurologic Dysfunction in Covid-19 (GCS-NeuroCovid) contributed one cohort with and without neurologic symptoms (n=3,055, mean age 60, 57% men) and a second cohort all of whom had neurologic symptoms (n=475, mean age 63, 55% men).
The European Academy of Neurology Neuro-Covid Registry (ENERGY), a prospective registry, contributed a third cohort that all had neurologic symptoms (n=214; mean age 57, 62% men).
The GCS-NeuroCovid study included people 18 or older with clinical or laboratory diagnosis of Covid-19, while ENERGY included patients 18 or older with a clinical Covid-19 diagnosis and a formal neurological consultation.
The researchers distinguished self-reported symptoms (headache, anosmia, ageusia, and history of syncope) from signs, syndromes, and diagnoses determined by clinical evaluation (acute encephalopathy, stroke, coma, seizure or status epilepticus, dysautonomia, meningitis or encephalitis, myelopathy, plegia and/or paralysis, aphasia, movement abnormalities, abnormal tone, abnormal brainstem reflexes, and sensory abnormalities).
Pooled incidence figures showed that the most common self-reported symptom was headache at 37%. Anosmia/ageusia occurred in 26%.
The most prevalent diagnosed neurologic concerns were acute encephalopathy (49%), followed by coma (17%) and stroke (6%). Least common were meningitis and encephalitis.
The presence of pre-existing neurological disorders was associated with increased risk of developing neurological signs or syndromes with Covid-19 (adjusted OR, 2.23, 95% CI, 1.80-2.75, P=0.17). Other factors associated with an increased risk of developing a diagnosed neurological sign or syndrome included age (OR per 10-year increment 1.41), male sex (OR 1.53), and White race (OR 0.62 for Asian versus White, and OR 0.80 for Black versus White).
Prior studies have included case series and single or regional cohorts with varying data definitions, “limiting the ability to accurately estimate the incidence of Covid-19 neurological manifestations and precluding data pooling and generalization across populations,” Chou and colleagues wrote.
Yet, with greater in-study knowledge of their own three cohorts, they also found value in not pooling data. “The presentation of the data as distinct cohorts allowed for precise reporting of parameters, which was needed to definitively build the science around these conditions within the setting of Covid-19 infection and to compare outcomes between patients with Covid-19 with and without neurological manifestations,” they noted.
Cohort-specific analysis highlighted variations based on region and cohort composition, they added. “Aggregating all data and presenting only pooled data could have resulted in inaccurate estimates and an overstatement of actual signs and syndromes,” they pointed out.
For example, variations have been seen in the incidence of common syndromes like stroke and coma. While prior work reported stroke incidence in Covid-19 patients ranging from 1% to 46%, the present study showed incidence of 3% overall, but a higher incidence of 19% in the cohorts that contained only patients with neurologic manifestations.
In this study, self-reported neurological symptoms (such as headache, anosmia or ageusia, syncope) were associated with a reduced risk of in-hospital death, while clinically captured neurologic signs or syndromes were associated with an increased risk of death, Chou and co-authors noted. The finding “may reflect ascertainment bias, where such data may be insufficiently captured in patients with higher disease severity, particularly in the hospitalized Covid-19 population,” they observed.
In addition, the time or duration of the neurological observation and its association to in-hospital mortality was not recorded and included in the analysis. “Particularly among those with advanced illness, this is an important consideration and should be included in future research,” the researchers wrote.
“Despite this limitation, our findings were consistent with the growing evidence from smaller cohort studies and supported the conclusion that neurological manifestations with Covid-19 are an important risk factor for mortality,” they added. “As such, a formal neurological consultation may be warranted when neurological signs or symptoms are suspected among individuals who test positive for Covid-19.”
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A global multi-cohort study showed that 82% of hospitalized Covid-19 patients had at least one new neurological symptom, sign, or syndrome. Acute encephalopathy was most common.
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Covid patients with clinically diagnosed neurological symptoms were six times more likely to die during acute hospitalization than those without neurological complications (adjusted OR 5.99, 95% CI 4.33-8.28, P<0.001).
Paul Smyth, MD, Contributing Writer, BreakingMED™
This study was supported by the National Institutes of Health, National Center for Advancing Translational Sciences, National Institute of Health, to Dr Chou, and the University of Pittsburgh Dean’s Faculty Advancement Award. Data collection for the European registry was supported by the European Academy of Neurology.
Chou reported no disclosures.
Cat ID: 190
Topic ID: 79,190,501,521,728,932,933,190,926,130,192,927,151,928,925,934
