April 10, 2020

expert reaction to paper on neurological manifestations of patients hospitalised with COVID-19 in Wuhan, China

A paper, published in JAMA Neurology, reports on neurological manifestations of patients hospitalised with COVID-19 in Wuhan.

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The observations of neurological complications in a subset of COVID-19 positive patients is worthy of note but should not distract from a focus on the main pathology of respiratory distress. Almost half of the patients described here had underlying health issues and there is no direct data given on the presence of virus at neurological sites. Viraemia, the presence of virus in the bloodstream, from where it can access neuronal tissue, was described for SARS but not in all patients and then only transiently. It happens, but is generally not what coronaviruses do. At the moment neurological complications might best be considered a consequence of COVID-19 disease severity rather than a distinct new concern.”

Dr Virginia Newcombe, Academy of Medical Sciences / Health Foundation Clinician Scientist Fellow, University of Cambridge, Honorary Consultant in Neurosciences Critical Care Unit, Addenbrookes Hospital, said:

“It is difficult to truly ascertain what conclusions can be made about the exact role of COVID-19 in the neurological manifestations seen in the patients described in this paper.

“What is not known is how much is driven by and a consequence of COVID-19 itself vs separate neurological disease presenting at the same time.  We therefore need to be cautious when stating covid-19 has caused specific signs and symptoms. There are initiatives to collect data both in the UK (lead by the Association of British Neurologists and the Neuroanaesthesia and Critical Care Society) and the USA (lead by the Neurocritical Care Society  https://www.neurocriticalcare.org/home) for both the acute and longer-term neurological manifestations of covid-19.  There are other initiatives worldwide which will help us understand better the short-term and longer-term neurological problems viruses like Covid-19 may lead to. 

“It is true many apparently neurological symptoms and signs can simply be a sign of being unwell with sepsis, having low oxygen (hypoxia) and treatments given (e.g. sedatives in ICU) and are common in patients with delirium. For example in the JAMA paper symptoms such as dizziness, headache and impaired consciousness are common when unwell and may not be indicative of a true neurological disorder. 

“In addition, some risk factors for worse disease with COVID-19 e.g obesity, hypertension, diabetes in themselves lead to a higher risk of stroke etc.  

“However, it is likely that for a subset of patients there will be true neurological impacts of COVID-19 infection. 

“There seems to be reported higher rates of both microvascular and macrovascular thrombosis, and this is certainly seen clinically in my experience. For example higher rates of deep vein thrombosis, strokes, clots elsewhere (lungs etc). The exaction mechanisms of this is unknown, as well as how best to prevent this. 

“The rates of other manifestations as mentioned above (e.g ataxia and seizure) are as yet unclear. The emphasis in current management is the management of the respiratory issues caused by COVID-19 (Pneumonitis, ARSDS etc) and it may be as our experience progresses other symptoms and signs are noticed. 

“In addition, simply being unwell enough to need intensive care treatment including ventilation may lead to “post intensive care syndrome” where some experience long-term cognitive impairment which may be secondary to the disease process that a person was admitted with in addition to the treatments required. In addition, being bed-bound and immobile in itself leads to loss of muscle mass and weakness that may need rehabilitation to recover from. 

“It should be remembered that the vast majority of people are likely to recover from COVID-19 without any of these complications – if they occur it will be in a minority. However, given the large number infected with COVID-19 worldwide it may still be a significant number of people.” 

More general comments on viral infections and neurological impacts:

“It is well described with previous viral pandemics that neurological sequelae can occur. The most famous example is from the “Spanish Flu” pandemic of 1918-1919 where “encephalitis lethargica” occurred in a proportion of those who got the flu. Characterised by symptoms which included confusion, an overwhelming desire to sleep and delirium type symptoms including sleep cycle reversal (sleep in the day and wake at night). Some patients became rigid with a “waxy flexibility” where they were rigid but could be re-positioned like dolls. The American Neurologist and author Oliver Sacks found dopamine could alleviate the symptoms which was the topic of the movie “Awakenings” with Robert de Niro and Robin Williams.” 

Prof Julian Hiscox, Chair in Infection and Global Health, University of Liverpool, said:

“These findings are not really surprising for SARS-CoV-2. We have known for over 30 years that human coronaviruses can be neuroinvasive and neurotropic.  For example, this has been found for human coronaviruses 229E and OC43 as well as SARS-CoV. Certain strains of murine (mouse) and feline (cat) coronaviruses also target neurons. Many respiratory viruses appear to not only affect the respiratory system but can spread from the airways to the central nervous system. Measles perhaps provides the best example of this.”

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China by Ling Mao et al. was published in JAMA Neurology at 16:00 UK time Friday 10 April.

All our previous output on this subject can be seen at this weblink: www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.