Neurological manifestations and neuro-invasive mechanisms of the severe acute respiratory syndrome coronavirus type 2

Epidemiological Neurology
Vonck K et al
Eur J Neurol

Main result

Neurological disorders were reported in 36.4% of an initial large series of 214 patients with a confirmed diagnosis of Covid-19.

Neurological symptoms were more frequent in patients with severe infection depending on their respiratory status (45.5% vs. 30.2% in non-serious cases) and were divided into three categories: central nervous system (CNS) manifestations (dizziness, headache, altered consciousness, acute cerebrovascular disease, ataxia, and convulsions), cranial and peripheral nervous system manifestations (alterations in taste, smell, vision, and neuropathy) and manifestations of skeletal muscle damage. Patients with severe respiratory infection were older, had more underlying disorders, and had less common symptoms such as fever and cough.

A retrospective study in Wuhan examining the clinical characteristics of 113 deceased patients with COVID-19 reported altered consciousness on admission in almost a third of the patients. A recent study of 2 intensive care units in Strasbourg found neurological symptoms on admission to intensive care in 14% (8/58) of patients with ARDS; 2/3 of the patients showed agitation when sedation and neuromuscular blockade were removed. In two-thirds of patients, signs of the cortico-spinal tract were detected. 

Among the patients already discharged, 1/3 had signs of a dysexecutive syndrome involving inattention, disorientation, or poorly organized movements in response to commands. 11/13 patients who received MRI for signs of encephalopathy, had bilateral frontotemporal hypoperfusion on perfusion imaging, and 2 had a small acute ischemic stroke with no clinical symptoms. In 7 of these patients who underwent spinal puncture, RT-PCR tests of CSF specimens were negative for SARS-CoV-2. In a retrospective analysis of patients admitted to a neuro-COVID unit in Italy, the patients (56/173) were found to have significantly higher mortality, delirium, and disability in hospital compared to neurology patients admitted in the same period without COVID-19.

A post-mortem cerebral MRI study conducted in Belgium in 19 patients revealed cerebral abnormalities in 8 non-survivors of COVID-19, including brain lesions related to the posterior reversible hemorrhagic encephalopathy syndrome.


There is growing evidence that SARS-CoV-2 infections are not always limited to the respiratory tract. 

There may be neurological manifestations, including acute cerebrovascular disease, altered consciousness, cranial nerve manifestations, and autoimmune disorders such as Guillain-Barré syndrome.

Both olfactory and taste dysfunctions are common in patients with mild to moderate COVID-19 who may not develop nasal symptoms. Most other neurological symptoms are seen in patients with more severe COVID-19 and are potentially due to generalized deregulation of homeostasis caused by major damage to the body's systems. However, part of the neurological manifestations in COVID-19 patients may be due to direct neurological injury by the virus or to indirect neuroinflammatory and autoimmune mechanisms and may occur rapidly during the course of the disease.

Detection of viral nucleic acid in the CSF is rare to date; detection of intrathecal synthesis of antiviral antibodies or brain autopsies in COVID-19 patients may clarify the viral capacity for CNS invasion. 

Strength of evidence Weak

- Literature review including retrospective and observational studies and case reports.


Description of neurological manifestations in patients with COVID-19 and possible neuroinvasive mechanisms of SARS-CoV-2.


Searches on Pubmed, WebOfScience and in databases dedicated to Covid-19 with the combination of various Covid-19 terminology (Covid-19, coronavirus, new coronavirus, SARS-Cov-2) and neurological terminology (neurological symptoms and manifestations, stroke, convulsions, epilepsy, MS, meningitis, headache, altered state of consciousness, ...) as well as neuroinvasive mechanisms until May 10, 2020.

Social networks (Facebook, Twitter, Linked-in) were monitored with the same scope between March 15 and May 10, 2020.

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