What is the incidence and clinical course of neurologic manifestations in patients with COVID-19?

Posted on May 4, 2020 by Gemma Percival

Summary

A number of case reports and observational studies document neurologic findings associated with COVID-19. These manifestations frequently occur early in the course of COVID-19 and can occur in absence of respiratory symptoms. The leading neurologic manifestations, with approximate incidence, include(8):

  • Dizziness (17%)
  • Headache (8%-14%)
  • Rhabdomyolysis (11%)
  • Confusion (9%)
  • Depressed level of consciousness (8%)
  • Ageusia (loss of taste) (6%)
  • Anosmia (loss of smell) (5%)
  • Ischemic or hemorrhagic stroke (3%)

I.   Clinical guidelines

Havard COVID-19 Clinical Guidelines

  • Excellent summary of neurological manifestations including incidence, pathophysiology, clinical course, and management.

II.   Incidence

III.   Clinical course

Apart from cerebrovascular disease and impaired consciousness, case studies suggest that most neurologic manifestations occur early in the illness (median time, 1-2 days) (3). Smell and taste disturbances occur mostly on day four of symptoms, while 13% experience disturbances on day one (9). 

Table from Herman et al. (2020 Apr 28)

 

Luers et al. (2020 May 1): Symptoms reported by 78 COVID positive patients in Germany

  1. General Headache (78%)
  2. Decreased smell  (74%)
  3. Decreased taste in (69%)
  4. Decreased smell + taste in (68%)
  • Smell and  taste disturbances mostly on day 4 of symptoms, but 13% have on day 1

Oxley et al. (2020 Apr 28): Case report of large-vessel stroke in five patients under 50 years old

  • Over a 2-week period five COVID-19 patients under the age of  50 presented with large-vessel ischemic stroke. By comparison the service treated, on average, 0.73 patients younger than 50 years of age with large-vessel stroke every 2 weeks over the previous 12 months.

Helms et al. (2020 Apr 15): Observational series of 58 patients admitted for ARDs secondary to COVID-19

  • The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment). Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued. 

Mao et al. (2020 Apr 10): A retrospective study of 214 COVID-19 patients in Wuhan, China

  • Neurologic symptoms were seen in 78 (36.4%) patients. 
  • In patients with CNS manifestations, the most common reported symptoms were dizziness (36 [16.8%]) and headache (28 [13.1%]). 
  • In patients with PNS symptoms, the most common reported symptoms were altered taste (12 [5.6%]) and smell (11 [5.1%]).
  • Of the six patients with acute stroke, two arrived at the emergency department owing to sudden onset of hemiplegia but without any typical symptoms (fever, cough, anorexia, and diarrhea) of COVID-19.
  • Neurological manifestations were more common in patients with severe infection compared with nonsevere infections (40 [45.5%] vs 38 [30.2%], P = .02). 
  • Compared with patients with nonsevere 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. 
  • Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5 [5.7%] vs 1 [0.8%]; P = .03), impaired consciousness (13 [14.8%] vs 3 [2.4%]; P < .001), and skeletal muscle injury (17 [19.3%] vs 6 [4.8%]; P < .001). 

Li et al. (2020 Mar 13) A retrospective study of 221 COVID-19 patients in Wuhan, China

  • Of 221 patients with COVID-19, 11 (5%) developed acute ischemic stroke, 1 (0·5%) cerebral venous sinus thrombosis (CVST), and 1 (0·5%) cerebral hemorrhage. 
  • COVID-19 with new onset of CVD were significantly older (71·6 ± 15·7 years vs 52·1 ± 15·3 years; p<0·05), more likely to present with severe COVID-19 (84·6% vs. 39·9%, p<0·01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes, and previous medical history of cerebrovascular disease (all p<0·05).

IV.   Current state of evidence

  1. Bingham and Women’s Hospital. COVID-19 Guidelines: Neurology [Internet]. 2020 Apr 24 (accessed 2020 Apr 300. Available from: https://covidprotocols.org/protocols/11-neurology/
  2. Boston Medical Centre. COVID-19 Neurology Protocols [Internet]. No date (accessed 2020 Apr 30). Available from: https://covidneurology.org/
  3. Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study [Internet]. JAMA. 2020 Apr 9 (accessed 2020 Apr 30). Available from: https://jamanetwork.com/journals/jamaneurology/fullarticle/2764549
  4. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C et al. Neurologic Features in Severe SARS-CoV-2 Infection [Internet]. N Engl J Med. 2020 Apr 15 (accessed 2020 Apr 30). Available from: https://www.nejm.org/doi/full/10.1056/NEJMc2008597
  5. Li Y, Wang M, Zhou Y, et al. Acute Cerebrovascular Disease Following COVID-19: A Single, Retrospective, Observational Study [Internet]. The Lancet 2020. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550025
  6. Herman C, Mayer K, Sarwal A. Scoping Review of Prevalence of Neurologic Comorbidities in Patients Hospitalized for COVID-19 [Internet]. Neurology. 2020 Apr 28 (accessed 2020 Apr 30). Available from: https://n.neurology.org/content/early/2020/04/24/WNL.0000000000009673 
  7. Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young [Internet]. N Engl J Med. 2020 Apr 28 (accessed 30 April 2020). Available from: https://www.nejm.org/doi/full/10.1056/NEJMc2009787?page=2#article_comments 
  8. Cleveland Clinic. Neurological Manifestations: What we know today. 2020 Apr 22 (accessed 2020 Apr 30). Available from: https://consultqd.clevelandclinic.org/neurologic-manifestations-of-covid-19-what-we-know-today/
  9. Luers JC, et al. Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19) [Internet]. Clin Infect Dis. 2020 May 1 [cited 2020 May 4]. Available from: 32357210.https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa525/5827752

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References

Disclaimer

The above is intended to serve as a rapidly-created, accessible source of information curated by medical students and healthcare professionals. It is for educational purposes only and is not a complete reference resource. It is not professional medical advice, and is not a substitute for the discretion, judgment, and duties of healthcare professionals. You are solely responsible for evaluating the information above.