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expert reaction a review and a case study looking at neurological manifestations associated with COVID-19 disease and other coronaviruses

A review, published in JAMA Neurology, looked at neurological manifestations associated with COVID-19 disease and other coronaviruses.


Prof David Werring, Professor of Clinical Neurology, UCL Institute of Neurology, said:

“This review paper summarises evidence for neurological syndromes in people with COVID-19.  Stroke – particularly due to arterial occlusion and ischaemia – is emerging one of the more common serious neurological complications of COVID-19, with many reports emerging in recent weeks.  The true prevalence of ischaemic stroke in patients with COVID-19 admitted to hospital is not yet certain, but early reports from China and Italy suggested this could be about 2-5% but more recent data from New York indicated a lower rate of about 1%.  There is now good evidence that a high proportion of ischaemic strokes in COVID-19 are associated with hypercoagulability, often with occlusion of large brain vessels and sometimes with concurrent venous thrombosis in the lungs or legs.  There is often evidence of marked inflammation, and strokes seem to occur from about 1-3 weeks from the onset of COVID-19 symptoms (though can rarely be the presenting symptom of COVID-19).

“Because the SARS-CoV-2 virus binds to receptors in blood vessel endothelium it is possible that endothelial damage is a key step in the hypercoagulable state and thrombosis.  Of course many patients with COVID-19 and stroke have other vascular comorbidities such as high blood pressure, diabetes or atrial fibrillation, so it seems likely that the prothrombotic and inflammatory effects of COVID-19 might interact with these conventional risk factors.  It is also becoming clear that ischaemic stroke in COVID-19 can be more severe than typical strokes, so early recognition, understanding of mechanisms and treatment (e.g. with anticoagulant drugs) are important.”


Dr Tim Nicholson, Clinical Senior Lecturer & Honorary Consultant Neuropsychiatrist, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said:

“The first paper: a high quality review summarising the many ways in which coronaviruses, so MERS-CoV (causing MERS) and SAR -CoV-1 (causing SARS) as well as SARS-CoV-2 (causing COVID-19) and their treatment (e.g. medication side effects) can affect the nervous system causing a range of symptoms ranging from relatively minor (headache) to severe (stroke).  There is no new data in this paper but it summarises the state of our current knowledge and possible mechanisms and a good reminder of the potentially severe effects of COVID-19 beyond the acute respiratory symptoms and that these should be looked out for and we might expect to see increased rates of these, and potentially other, symptoms and disorders as the pandemic progresses.

“The second paper: an intriguing single case report of a radiographer with COVID-19 associated loss of smell (anosmia) and taste (dysgeusia) who had a (MRI) brain scan providing evidence that these symptoms might be due to direct brain invasion by the virus (rather than another cause such as nasal lining (epithelial) changes) by showing changes in brain structure in brain regions involved in detecting smells and taste that normalised when the symptoms later recovered.  As it is only a single case caution is needed in extrapolating this to other cases but it adds interesting supportive data and indicates a method of investigating the cause of this interesting and common symptom of COVID-19.”


Prof John Hardy, Professor of Neuroscience, UCL, said:

“It has become increasingly clear that covid affects more than the lungs and can cause problems in many organs, now this research suggests those affects might include areas of the brain involved with smell.  In my view, of particular importance is that the symptoms may give clues as to the route of infection.  Olfaction loss suggests, perhaps, infection through the nose, and similar suggestions may relate to other iinitial symptoms.  This type of analysis may possibly help guide us as to public health measures which need to be undertaken to reduce infection.”


Dr Michael Zandi, Consultant Neurologist National Hospital for Neurology and Neurosurgery, and Honorary Associate Professor, UCL Queen Square Institute of Neurology, UCL, said:

“A striking feature of SARS-CoV-2 infection has been the loss of sense of smell and taste in some individuals affected, often providing a key clue of infection with this virus.  The study by Politi and colleagues provides some evidence that the virus itself may affect the brain in some cases.  The authors demonstrate transient brain imaging changes that are seen in adjacent brain areas to the nose and olfactory nerves, using MRI in one patient who had severe and transient loss of the sense of smell (and some altered taste) with SARS-CoV-2 infection.  The temporary nature of the changes is reassuring.

“We know from previous research1,2 that some individuals who have had SARS-CoV-2 infection may develop neurological and psychiatric symptoms (these are large studies but often biased to those reported in hospitals with severe illness where testing available, and we are missing the milder symptoms).  What remains to be seen is to what extent symptoms are due to viral infection of the brain itself, or secondary effects including inflammation in the brain triggered by the immune system’s response to the virus, and in others stroke due to blood becoming more likely to clot for example.

“Detailed clinical studies of the brain in individuals who have had SARS-CoV-2 infection, including brain imaging, spinal fluid and blood analysis, and study of pathological specimens including post-mortem where available will help us understand what exactly is going on and help us treat those with serious brain and nerve involvement.  Zubair and colleagues review some of the mechanisms by which the SARS-CoV-2 virus may infect brain cells directly, and related secondary effects.”





Review: ‘Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019: A Review’ by Adeel S. Zubair et al. will be published in JAMA Neurology at 16:00 UK time on Friday 29 May 2020, which is also when the embargo will lift.

DOI: 10.1001/jamaneurol.2020.2065

Case study: ‘Magnetic Resonance Imaging Alteration of the Brain in a Patient

With Coronavirus Disease 2019 (COVID-19) and Anosmia’ by Letterio S. Politi et al. will be published in JAMA Neurology at 16:00 UK time on Friday 29 May 2020, which is also when the embargo will lift.

DOI: :10.1001/jamaneurol.2020.2125


All our previous output on this subject can be seen at this weblink:


Declared interests

None received.

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