Manifestations more common with severe Infection

More than a third of laboratory-confirmed Covid-19 patients had neurologic symptoms, an early observational case series from Wuhan, China, found.

Symptoms seen in 36.4% of 214 consecutive cases seen in Wuhan during January and February of 2020 included:

  • Central nervous system manifestations: dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, seizure.
  • Peripheral nervous system manifestations (taste impairment, smell impairment, vision impairment, or nerve pain).
  • Skeletal muscular injury manifestations.

Acute cerebrovascular diseases, impaired consciousness, and skeletal muscle injury were more common (45.5%) in those classified at admission as having severe infection (defined by American Thoracic Society guidelines for community-acquired pneumonia) and requiring mechanical ventilation. In those with non-severe disease, neurologic symptoms were present in 30.2%.

“During the epidemic period of Covid-19, when seeing patients with these neurologic manifestations, clinicians should consider SARS-CoV-2 [the virus causing Covid-19] infection as a differential diagnosis to avoid delayed diagnosis or misdiagnosis and prevention of transmission,” wrote Bo Hu, MD, PhD, of Union Hospital of Huazhong University of Science and Technology in Wuhan and colleagues in JAMA Neurology.

Late in 2002, severe acute respiratory syndrome (SARS) appeared and began spreading in Asia, a viral pneumonia with severe lung injury and widespread vasculitis. Neurologic complications appeared in some patients 2 to 3 weeks into SARS, including either axonal peripheral neuropathy or myopathy with elevated creatinine kinase. Large-vessel strokes were also noted in a small number, and one case of olfactory neuropathy with onset 3 weeks into the illness was reported.

In December 2019, unexplained viral pneumonia cases in Wuhan began to spread due to a novel coronavirus with the same angiotensin converting enzyme 2 (ACE2) receptor and similar symptoms as SARS. This disease, Covid-19, had clinical manifestations including fever, cough, fatigue, shortness of breath, and sputum production. Atypical presentations also were described.

In light of the sparse history of neurologic manifestations of SARS, this report about Covid-19 patients in Wuhan is important, noted S. Andrew Josephson, MD, of the University of California, San Francisco and coauthors, in an accompanying editorial. “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,” they wrote.

Hu and colleagues collected data on 214 consecutive laboratory-confirmed Covid-19 patients from three designated special care centers of Union Hospital in Wuhan between January 16 and February 19, 2020. Mean age was about 53 years and 41% were men. In this sample, 5.6% of patients had taste impairment, 5.1% had smell impairment, 1.4% had vision impairment, and 2.3% had nerve pain.

Nearly 60% of the 214 patients had non-severe infection; the remainder had severe infection. Patients with severe infection were older, had more underlying disorders especially hypertension, and showed fewer typical symptoms of Covid-19, such as fever and cough.

Severe versus non-severe infections showed respective rates of:

  • Acute cerebrovascular diseases: 5.7% versus 0.8%.
  • Impaired consciousness: 14.8% versus 2.4%.
  • Skeletal muscle injury: 19.3% versus 4.8%.

The fact that stroke and impaired consciousness were more common with severe illness “should be considered in light of our understanding that patients with severe complications from SARS-CoV-2 are more likely to have medical comorbidities, especially vascular risk factors such as hypertension,” Josephson and co-authors noted.

“The occurrence of cerebrovascular events in critically ill patients with underlying high blood pressure and cardiovascular disease is therefore potentially unrelated to a direct effect of the infection itself or an inappropriate host response,” they pointed out.

Dividing neurologic symptoms into specific (e.g., loss of smell or taste; stroke) and non-specific (e.g., headache, depressed level of consciousness, dizziness, or seizure), the editorialists noted that specific symptoms tended to occur early in the clinical course. “This appears to be quite distinct from SARS, where manifestations appeared quite late in established disease,” they wrote. Because of this, “neurologists may be confronted by patients presenting with new onset neurologic symptoms and should be potentially concerned that these could be owing to Covid-19,” they continued.

The SARS studies raise questions of whether axonal neuropathy will be seen with Covid-19, but the Wuhan case series “was unable to shed clear light on these questions because the authors were unable to pursue detailed electromyography/nerve conduction studies or lumbar puncture in their patients owing to concerns about the pandemic and highly infectious nature of Covid-19,” Josephson and colleagues added.

This study has several limitations, Hu and co-authors noted. Only 214 patients were studied, and all were from Wuhan, which could create bias. The effect of neurologic manifestations on patient outcome was not assessed. All data came from electronic medical records; some patients with neurologic symptoms might not have been captured if their manifestations were mild, they added.

  1. More than a third of Covid-19 patients seen in Wuhan, China in January and February 2020 had neurologic symptoms.

  2. Neurologic symptoms including stroke, alteration in conscious level, and loss of taste or smell were more common with severe infection (defined by whether ventilation was required), but so were cardiovascular comorbidities.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, and Major Refractory Diseases Pilot Project of Clinical Collaboration with Chinese and Western Medicine.

The researchers reported no conflicts of interest.

Josephson reported personal fees from JAMA Neurology and from Continuum Audio outside the submitted work.

Cat ID: 130

Topic ID: 82,130,287,500,728,932,125,190,469,520,926,130,192,927,150,151,928,925,934

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