What is the incidence and clinical course of neurologic manifestations in patients with COVID-19?Posted on by
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
- Excellent summary of neurological manifestations including incidence, pathophysiology, clinical course, and management.
- Unknown overall incidence but likely common (2)
- Neurologic manifestations may occur in 36.4%-69% of hospitalized COVID-19 patients (3; 4).
- Delirium, confusion, or executive dysfunction are particularly common, and may occur in a majority of hospitalized patients (4).
- Other common neurologic manifestations are dizziness (16.8%), headache (13.1%), impaired consciousness (7.5%), hypogeusia (5.6%), hyposmia (5.1%) (3)), or stroke (2.8-5%) ((3, 5).
- New case reports of rarer complications are emerging(1):
- GBS (Toscano, NEJM, 2020; Zhao, Lancet Neurol, 2020), Miller-Fisher syndrome (Gutierrez-Ortiz, Neurology, 2020)
- Encephalitis (Moriguchi, Int J Inf Dis, 2020; Ye, Brain Behav Immunity, 2020; Duong, Brain Behav Immun, 2020)
- Acute necrotizing encephalopathy (Poyiadji, Radiology, 2020)
- Myelitis (Zhao, medRxiv 2020)
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).
- General Headache (78%)
- Decreased smell (74%)
- Decreased taste in (69%)
- Decreased smell + taste in (68%)
- Smell and taste disturbances mostly on day 4 of symptoms, but 13% have on day 1
- 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.
- 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.
- 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).
- 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
- 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/
- Boston Medical Centre. COVID-19 Neurology Protocols [Internet]. No date (accessed 2020 Apr 30). Available from: https://covidneurology.org/
- 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
- 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
- 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
- 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
- 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
- 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/
- 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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