Results from one of the first multi-case studies of neurologic manifestations of COVID-19 demonstrate complex CNS involvement and raise further questions about pathological mechanism.
Neurologic symptoms, including central and peripheral nervous system and skeletal muscular manifestations, are commonly reported in patients with confirmed infections of COVID-19, according to clinical data from a retrospective case series published in JAMA Neurology.1
The report is arguably the first multi-case series of neurologic manifestations of SARS-CoV-2. The data were extracted from electronic health records of patients treated at the Union Hospital of Huazhong University of Science and Technology in Wuhan, China, the epicenter of the pandemic. With currently over 1.6 million cases reported globally and nearly 475,000 in the US alone, reports of neurologic complications and manifestations have begun to surface, though their connection to the novel respiratory illness is still unclear.
Earlier this week, investigators out of Henry Ford Hospital System in Detroit, Michigan published what is thought to be the first case of acute necrotizing encephalopathy in a patient with confirmed COVID-19 infection who presented with fever, cough, and altered mental status.2 There have been various other reports of cerebrovascular events, as well as impacts on sense of smell and taste, among others, that may be related to the infection.
In this study, investigators led by Bo Hu, MD, PhD, of the department of neurology, Union Hospital, Tongji Medical College at Huazhong University of Science and Technology in Wuhan, China, retrospectively reviewed data collected from 214 patients between January 16 and February 19, 2020. The patients had laboratory-confirmed SARS-CoV-2.
Of the 214 patients included in the analysis, mean age was 52.7 years and just over 40% were male. Based on respiratory status, 58.9% (n = 126) had nonsevere infection and 41.1% (n = 88) had severe infection, and 38.8% had at least 1 underlying disorder, including hypertension, diabetes, cardiac or cerebrovascular disease, or malignancy. Of those infected, 36.4% (n = 78) had neurologic manifestations, which were categorized as central nervous system (CNS) manifestations (dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system (PNS) manifestations (taste impairment, smell impairment, vision impairment, and nerve pain), or skeletal muscular injury manifestations.
At illness onset, the most commonly reported symptoms were fever (61.7%), cough (50%), and anorexia (31.8%), though notably, those with more severe disease had fever typical symptoms of COVID-19. Among the 78 patients who presented with neurologic manifestations, they were more likely to have severe infection (40 [45.5%] vs 38 [30.2%], P = .02), with 53 categorized as having CNS, 19 as PNS, and 23 as skeletal muscular manifestations, with the most commonly reported symptoms in the CNS group being dizziness (16.8%) and headache (13.1%), and taste and smell impairment (5.6%; 5.1%) in the PNS group.
Other nervous system manifestations included acute cerebrovascular disease (5.7%), with 4 patients experiencing ischemic stroke and 1 with cerebral hemorrhage (P = .03), impaired consciousness (P <.001), and skeletal muscular injury (P <.001).
Notably, most neurologic manifestations presented early on in the illness, with several reports of patients who experienced cerebrovascular disease and headache admitted to the hospital without symptoms of COVID-19 only to test positive several days later.
“We need to pay close attention to their neurologic manifestations, especially for those with severe infections, which may have contributed to their death. Moreover, during the epidemic period of COVID-19, when seeing patients with these neurologic manifestations, physicians should consider SARS-CoV-2 infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and prevention of transmission,” the investigators wrote.
Other differences observed between severe and nonsevere cases included higher white blood cell counts, neutrophil counts, lower lymphocyte counts, and increased C-reactive protein levels compared to those with nonsevere infection (P < .001 for all), in addition to high D-dimer levels and multi-organ involvement, including serious liver, kidney, and skeletal muscle damage.
“It is clear that this small series does not reflect the entire spectrum of neurologic disease in COVID-19 disease, and much is left to be learned with thorough neurologic testing in large data sets of patients with COVID-19,” Samuel J. Pleasure, MD, PhD; Ari J. Green, MD; and S. Andrew Josephson, MD, wrote in a related editorial.3 “As the means for reliably assessing infection and prior exposure become available, less common neurologic complications should be anticipated; however, this glimpse into neurologic manifestations opens a window into neurologists’ role and places them on the front lines of the pandemic.”
1. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1127
2. Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology. 2020;:201187. DOI: 10.1148/radiol.2020201187
3. Pleasure SJ, Green AJ, Josephson SA. The spectrum of neurologic disease in the severe acute respiratory syndrome coronavirus 2 pandemic infection: neurologists move to the frontlines. JAMA Neurol. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1065