More than half of COVID-19 patients admitted to two hospitals in Spain developed some form of neurologic symptoms, a retrospective, observational study showed.
Neurologic manifestations were seen in 57.4% of 841 patients hospitalized with COVID-19 in March, reported Carlos Manuel Romero-Sanchez, MD, of Complejo Hospitalario Universitario de Albacete in Spain, and co-authors in .
In 4.1% of COVID-19 deaths in the study, neurologic complications were considered the fundamental cause.
This is the largest hospital-based study of COVID-19 patients to analyze neurologic symptoms systematically, the researchers noted.
Neurologic symptoms emerged throughout all phases of COVID-19 infection. Potentially severe conditions, like stroke and inflammatory diseases, appeared in late COVID stages, Romero-Sanchez said.
"We would like to raise awareness that neurological complications may arise in the recovery phase of COVID-19, including cerebrovascular and dysimmune," he told 鶹ý. "Optic neuritis and acute inflammatory demyelinating polyradiculoneuropathy are two examples."
In the study, one in five patients (19.6%) hospitalized with COVID-19 had disorders of consciousness. "Disorders of consciousness were associated with severe COVID, older age, higher creatine kinase levels, and lower lymphocyte count," Romero-Sanchez noted.
Disorders of consciousness were nearly twice as high (38.9%) among patients with severe COVID-19 (with by 2007 Infectious Diseases Society of America/American Thoracic Society criteria). Most cases of altered consciousness were secondary to severe hypoxemia, the researchers noted. Of patients with severe COVID-19, 14.9% had delirium and 9.4% had coma.
Across all 841 hospitalized COVID-19 patients, myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), and hyperkinetic movement disorders (0.7%) occurred. Cerebrovascular diseases included 11 patients (1.3%) with ischemic stroke and three patients (0.4%) with intracranial hemorrhage.
"More than one-third of ischemic strokes involved posterior arterial territories, an unusual proportion," Romero-Sanchez pointed out.
"Moreover, we had some cases of otherwise unexplained vertebro-basilar dissection and also one case of multiple cortical hemorrhages associated with brain MRI pattern resembling posterior reversible encephalopathy syndrome," he added. "Although our study is mainly descriptive, we hypothesize that SARS-CoV-2 [the virus that causes COVID-19] may carry special tropism towards posterior circulation and endotheliopathy may be suggested."
In the study, nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were common. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early -- 60% of the time they occurred, they were the first clinical manifestation of COVID-19 -- and were more frequent in less severe cases. One case each of encephalitis, Guillain-Barré syndrome, and optic neuritis emerged.
The analysis was a systematic review of all patients diagnosed with COVID-19 in the AlbaCOVID registry. Patients had been admitted to two Spanish hospitals, Complejo Hospitalario Universitario de Albacete and Hospital General de Almansa, from March 1 to April 1, 2020. They had a confirmed laboratory diagnosis of COVID-19, either with a positive result for IgG/IgM antibodies against SARS-CoV-2 in a blood test or through detection of SARS-CoV-2 RNA with a real-time reverse transcription-polymerase chain reaction of throat swab samples.
In total, 329 patients (39%) had severe COVID-19. Seventy-seven patients were admitted to the ICU, and 197 patients died during the course of their hospital admission. Neurologic complications were considered the fundamental cause of patient death in eight cases (4.1% of total deaths).
Overall, patients were an average age of 66 and 56% were men. Those with severe disease were older than those with mild disease (71 years vs 63 years; P<0.001). Sex was not a risk factor for severe prognosis.
Hypertension (55.2%), obesity (44.5%), dyslipidemia (43.3%), tobacco smoking (36%), diabetes mellitus (25.1%), and heart disease (18.8%) were the most common systemic comorbidities. In multivariate analysis, obesity was the only independent predictor for severe COVID-19 (OR 3.06, 95% CI 1.41-6.67, P=0.005).
The researchers were unable to demonstrate direct invasion of the central nervous system (CNS) in this study; all CNS analyses were negative for viral RNA. They couldn't determine whether neurologic problems stemmed from SARS-CoV-2 infection or other factors like cross-immunity, inflammatory reaction, or side effects of treatment.
The pandemic context prevented a full neurologic exam of every hospitalized COVID-19 patient and selection bias may have occurred, Romero-Sanchez and co-authors noted. They added that the study is hospital-based and does not reflect the incidence of neurologic complications of COVID-19 patients in the community.
Disclosures
No targeted study funding was reported.
The authors reported no disclosures relevant to the manuscript.
Primary Source
Neurology
Romero-Sánchez CM, et al "Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry" Neurology 2020; DOI: 10.1212/WNL.0000000000009937.