June 25, 2020

expert reaction to study looking at brain complications in hospitalised patients with severe COVID-19

Research, published in The Lancet Psychiatry, looked at brain complications in hospitalised patients with severe COVID-19.

Dr Musa Sami, Clinical Associate Professor of Psychiatry, University of Nottingham, said:

“I would suggest it is important to keep these results in perspective. This study was widely advertised to psychiatrists nationally with repeated email reminders. The study closed on the 26th April 2020. By 27th April in the UK there were 150,000 confirmed cases of COVID-19 and 20,000 people had died. Despite this, this nation-wide surveillance programme identified 4 cases of anxiety and depression, 10 cases of psychosis and 6 cases of neurocognitive disorder. This data may suggest that if COVID-19 psychiatric conditions do exist they are rare.”

Prof Eduard Vieta, Chair of Department of Psychiatry and Psychology and Professor of Psychiatry, University of Barcelona, said:

“This is a descriptive, surveillance study on neuropsychiatric complications occurring in Covid-19 patients. It is important to remark that not all the complications can be attributed to the virus and in fact some can be quite unspecific, especially those labelled as “encephalitis” and “encephalopaty”, which can occur in the context of any severe medical condition, and especially in those that involve severe respiratory failure. Moreover, it is important to be aware that this sample comes from specialists and hospitals and therefore include the most extreme end of the spectrum of Covid patients as regards to severity, and that no conclusions can be drawn as regards to incidence and prevalence. Nevertheless, it represents a remarkable effort to identify the most severe neuropsychiatric complications of Covid-19, and it has done in a valid and systematic way. I think that what has been found is expectable from a virus infection that can be severe in some patients, and the next step should be to design protocols to prevent effectively these potential complications.”

Dr Sarah Sullivan, Research Fellow, University of Bristol, said:

“The press release is a good reflection of the scientific findings reported in the paper. The findings are interesting but should be interpreted with caution. For instance, as the authors note, this is just a (smallish compared to the number with severe infection) sample, which is likely to be affected by selection bias. The sample relied on reporting by specialist clinicians – who knows the reason why some clinicians were motivated to report cases and some weren’t. Another important issue is the lack of a control group, which is also acknowledged by the authors. We have nothing to compare the reports of severe complications to, for example those with severe infections but no neurological or other complications. We certainly cannot extrapolate these findings to those with milder infections, although loss of smell and taste in this group is likely to be due to neurological damage. The proportion with new onset psychosis is much greater than it would be in the healthy population, but again this could be due to selection bias, reporting bias by clinicians and even detection bias.

“This is a very interesting and well conducted study and the findings are certainly interesting and should form the basis of longitudinal, international, observational studies on a large scale into order to better understand the causal association between COVID 19 and psychiatric disorders. I think it is too soon to be too worried about this but longitudinal research needs to be funded now so that appropriate service planning can be carried out.”

Prof Richard Morriss, Professor of Psychiatry, University of Nottingham, said:

“The surveillance study published in Lancet Psychiatric is an important first step to discovering immediate neurological and psychiatric complications of COVID-19, especially to understand its pathophysiology. However, this approach will need to be complimented by less selected cohort studies following patients who have had COVID-19 over time to understand the long term implications of contracting COVID-19. In this paper and other data, the prevalence of psychiatric complications of severe COVID-19 in hospitalised patients seems highest in working age adults, but this is an emerging picture and there may be other factors at play. The institute of Mental Health at the University of Nottingham is currently engaged in a number of studies exploring some of these issues, often working as part of a network of centres nationally and internationally.”

Dr Celso Arango, Director, Institute of Psychiatry and Mental Health, Chair, Department of Child and Adolescent Psychiatry,  Hospital General Universitario Gregorio Marañon and Past President of European College of Neuropsychopharmacology (ECNP), said:

“This is a clinically relevant study that, despite the low number of cases reported, highlights that SARS-COV-2 can manifest in many different forms including, occasionally in severe hospitalised cases, neuropsychiatric conditions. As happens many times in neurology/psychiatry, the same factor (in this case SARS-COV-2) affecting the brain is associated with psychiatric conditions in younger patients and neurological conditions in elder patients.

“This work highlights the importance of interdisciplinary work and data sharing in clinical neuroscience and how samples can be recruited in a very short period of time (less than 25 days) to help clinicians around the world.

“The major limitation of the study is that the portal for psychiatrists to report was open very late, a few days before the study finished and therefore the number of cases may be biased towards the neurological ones as they had more time to be reported. Despite that, the relatively high proportion of psychiatric cases among young subjects needs further study. Specifically it would be very interesting to follow up the patients with a first psychotic episode to assess if it resolves with time or continues to be a chronic psychotic disorder (e.g. schizophrenia). An additional limitation is that causality cannot be attributed as some of the cases may be independent from the covid-19 infection.”

Prof Dame Til Wykes, Vice Dean Psychology and Systems Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said:

“This is an impressive scientific collaboration that is collecting information on a range of neurological and psychiatric symptoms that may be linked to severe Covid-19. Unfortunately the paper concentrates on the collaboration and doesn’t have enough exploration of the implications of the numbers of cases they are finding.”

“We have known that there were mental health problems associated with the pandemic which are seen in all communities but mostly in frontline healthcare staff, carers and people who already have mental health difficulties, which has been due to indirect impacts of the virus. We also expected some mental health problems to be experienced by those who have had Covid-19.

“We thought that these problems would just be increases in anxiety and depression but clearly there is a possibility that a small number of people may experience a first episode of psychosis following hospitalisation with severe Covid-19 – 8% of the total cases reported in this paper (10/125).

“There are clinical reports suggesting that serious mental illness might occur because of the stresses of lockdown, social distancing and financial worries. We need data on the general population to understand whether the psychosis risk is a direct effect of Covid-19 or a result of these social stresses or both.”

“What this study highlights is the additional needs for mental health support and services following Covid-19. We need to be prepared not just for the potential problems later but for problems right now. We need to invest in training psychologists, psychiatrists and mental health nurses and in support services that will help people with mental health difficulties to recover.”

Prof Michael Sharpe, Professor of Psychological Medicine, University of Oxford, said:

“This report describes often striking cases of neurological and psychiatric illness as being sometimes associated with severe COVID-19 in hospitalised patients. It reminds us that COVID-19 is more than a respiratory infection and that we need to consider its link to variety of other illnesses.

“However, because this is only a series of case reports of patients seen by certain types of hospital specialists, we cannot be certain that these illnesses were in fact caused by COVID-19 or were simply co-occurring. Additionally, we cannot estimate how common these illnesses are in the wider population of people who develop COVID-19.  We do need to do research to address these uncertainties. However at present people in the general population should not worry too much about these possibly associated illnesses as they are probably relatively rare in those who become infected with this coronavirus.”

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

“It is increasingly recognised that COVID-19 does not just affect the respiratory system; there have been reports, mainly small case series, of neurological complications affecting the brain, including stroke and encephalitis (brain inflammation), in patients with severe COVID-19, although these seem to be fairly rare. This paper reports data from a national co-ordinated surveillance system – set up at the beginning of April – at the time when COVID-19 cases were rapidly increasing in the UK – by multiple professional neuroscience organisations. The aim was to determine the spectrum of neurological complications associated with COVID-19. They received 153 separate case notifications and report on 125 of these; the most common neurological problem was stroke (in 62%) followed by altered mental status, mainly classified as an “encephalopathy” (non-specific brain dysfunction). These data are an important step in outlining the type of brain problems that can be associated COVID-19 in the UK.

“However, there are many further questions that need to be answered. First, this study cannot tell us the risk of neurological complications in people with COVID-19, although given the number of cases reported here, only a small minority seem likely to be affected. Second, we do not know whether COVID-19 increases the risk of brain complications more than other similar viruses. And third, this study does not provide enough detail to tell us about the possible mechanisms by which COVID-19 might cause neurological complications. We know that the virus can bind to the blood vessel lining (endothelial) cells, and in some people can cause delayed severe inflammation and increased blood clotting; understanding these mechanisms will be crucial to knowing how treatments might be able to reduce the risk of brain complications from COVID-19.”

Prof Paul Garner, Director of the Centre for Evidence Synthesis in Global Health, Liverpool School of Tropical Medicine, said:

“I am concerned that it is too early for confident psychiatric diagnoses in patients with severe COVID-19 who are experiencing symptoms that are used in the diagnosis of long term psychiatric illnesses.

“The paper says: The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist. Only two (9%) of 23 patients had exacerbations of existing enduring mental illness. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and seven (30%) had an other psychiatric disorder, including one case of catatonia and one case of mania.

“My concern is that this is a classic case of doctors putting things in boxes. People have symptoms and then doctors diagnose them against pre-existing understanding, but in this case we do not yet understand what is happening with patients with COVID-19, nor do we know the natural course of the Covid19 neurologic, psychological, or psychiatric symptoms. There are many more questions to be answered and studies to be done before we can confidently say if COVID-19 causes psychiatric disorders such as psychosis.”

‘Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study’ by Varatharaj et al was published in The Lancet Psychiatry at 23:30 UK Time Thursday 25^th June 2020.

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

Declared interests

Prof Michael Sharpe: No conflicts

None others received.