Neurological symptoms occur often in COVID-19, increase in-hospital mortality

Neurological manifestations occurred frequently in patients hospitalized with COVID-19 and correlated with increased in-hospital mortality, according to findings from a multicohort study published in JAMA Network Open.

The study also showed a relationship between pre-existing neurological conditions and a greater risk for developing neurological signs and/or symptoms in COVID-19.

“This study is the first report from the Global Consortium Study of Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID), which is an international, multicenter study on neurological dysfunctions in COVID-19,” Sherry H-Y Chou, MD, MMSC, FNCS, associate professor of critical care medicine, neurology and neurosurgery in the department of critical care medicine at the University of Pittsburgh, told Healio Neurology. “In this particular study, we looked at three cohorts of COVID-19 patients sick enough to require hospitalization, systematically determined the frequency of their neurological symptoms and signs, and looked at how these factors affected the patient’s risk of dying during acute hospitalization.”

Study results

Chou and colleagues conducted a cohort study of patients with clinically diagnosed or laboratory-confirmed COVID-19 from 28 centers in 13 countries. The study included the GCS-NeuroCOVID group, which conducted research from March 1, 2020, through September 30, 2020, and the European Academy of Neurology (EAN) Neuro-COVID Registry (ENGERY), which conducted research from March through October 2020. The researchers stratified patients into three groups: the GCS-NeuroCOVID all COVID-19 cohort (n = 3,055), which included consecutive hospitalized patients with COVID-19 with and without neurological manifestations; the GCS-NeuroCOVID COVID-19 neurological cohort (n = 475), which comprised consecutive patients hospitalized with COVID-19 who had confirmed neurological manifestations; and the ENERGY cohort (n = 214), which included patients with COVID-19 who received formal neurological consultation.

The researchers categorized neurological phenotypes as self-reported symptoms or neurological signs and/or syndromes according to clinical evaluation. They reported the composite incidence for groups with at least one neurological manifestation. In-hospital mortality served as the main outcome measure, according to the study results.

The all COVID-19 cohort included 1,742 men (57%) and the mean age of patients was 59.9 years (95% CI, 59.3-60.6 years). The COVID-19 neurological cohort included 262 men (55%) and the mean age of patients was 62.6 years (95% CI, 61.1-64.1 years). The ENERGY cohort included 133 men (62%) and the mean age of patients was 67 years (95% CI, 52-78 years).

In total, 3,083 patients (82%) across all groups (n = 3,743) experienced neurological manifestations of COVID-19, either those that were self-reported and/or identified clinically. The most frequent-self reported symptoms included headache (37%) and anosmia or ageusia (26%), according to the study results. The most predominant neurological signs and/or syndromes included acute encephalopathy (49%), coma (17%) and stroke (6%). Meningitis and/or encephalitis occurred infrequently (0.5%), Chou and colleagues found.

The incidence of clinically identified neurologic signs and/or syndromes in COVID-19 correlated with a greater risk for in-hospital mortality after adjustment for study site, age, sex, race and ethnicity (adjusted OR = 5.99; 95% CI, 4.33-8.28). Chou and colleagues also identified a link between the presence of pre-existing neurological disorders and a greater risk for developing neurological signs and/or syndromes with COVID-19 (aOR = 2.23; 95% CI, 1.8-2.75).

‘Important’ take-home messages, future research

The first report from the GCS-NeuroCOVID group demonstrated several “important take-home messages,” according to Chou. These included the fact that neurological symptoms and syndromes occurred commonly in patients with COVID-19 ill enough to require hospitalization.

“More than one in two patients who are hospitalized with COVID-19 experience some sort of neurological symptoms or dysfunction,” Chou said. “By far, the most common neurological syndrome seen in hospitalized patients with COVID-19 is acute encephalopathy, meaning that the patient is not themselves, are confused, delirious, agitated or have altered sensorium. The least common, or most rare neurological syndromes, are meningitis/encephalitis.”

Additionally, patients with COVID-19 and clinically verified neurological syndromes experienced “a much higher risk of dying during acute hospitalization,” even after accounting for the effects of older age, sex, differences in race and ethnicity and differences in death rates at different hospitals, Chou said. Specifically, patients with acute encephalopathy in this study were more than five times more likely to die during acute hospitalization for COVID-19 compared with those without encephalopathy.

The first report from the GCS-NeuroCOVID group demonstrated that the impact of neurological problems with COVDI-19 “is significant,” she continued.

“For the medical community, the first step is for us to become more vigilant and look out for neurological problems in patients hospitalized with COVID-19 so that we can detect and diagnose these conditions as early as possible,” Chou said. “Patients who already have a history of neurological problems in the past are particularly vulnerable for new neurological problems, which we now know is linked to a higher risk of dying. Clinicians and health systems may need to consider directing available resources to provide additional care and support to COVID-19 patients with neurological problems.”

An “important next step” for this research involves examining the longer-term neurological issues and outcomes in patients who survive following hospital discharge, Chou said, noting that survivors of COVID-19 “may continue to experience significant disability and long-term consequences” because of neurological problems that developed during the acute phase of COVID-19 infection or afterward.

“Recovery from neurological conditions is often incomplete and may take a very long time. When we consider the large number of people who have had COVID-19 and were sick enough to need hospitalization and the fact that one in two of them may have had neurological problems with COVID-19, this means we may have a large number of COVID-19 survivors suffering long term disability and consequences from neurological problems,” she said. “This is an important public health concern and we urgently need to learn more about the neurological consequences of COVID-19.”