January 27, 2021

expert reaction to COVID and schizophrenia

A study as published in JAMA Psychiatry looks at Psychiatric Disorders and mortality among COVID-19 patients.

Prof James MacCabe, Professor of Epidemiology and Therapeutics, Institute of Psychiatry Psychology and Neuroscience, Kings College London, said:

“The increased death rate from COVID-19 in people with schizophrenia is a cause for concern. We know that people with severe mental illness have higher overall mortality and often face reduced access to healthcare. They may be less likely to present to healthcare settings, and may be subject to healthcare rationing in some settings. These disparities in access to healthcare may be especially severe in the USA, where this study was conducted. To put the findings into context, the magnitude of the effect is comparable to that seen in physical health conditions including diabetes and neurological diseases. Crucially, this study did not take obesity into account which may account for some or even all of the effect. The most closely comparable study is probably that conducted in South Korea, which found that people with depression were slightly more likely to die from COVID-19 than schizophrenia, suggesting that these findings may vary in different healthcare systems. It will therefore be important to examine this effect in the UK and to address inequalities in access to healthcare in people with severe mental illness.”

Dr Sameer Jauhar, Senior Research Fellow and JMAS Sim Fellow, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said:

“We have known for a number of years that people with major mental illness, such as schizophrenia, have decreased life expectancy, which varies depending on the country and health system, and can be as much as 10-15 years less than the general population.

“There is an older literature from around ten years ago, suggesting that people with schizophrenia and pneumonia were almost twice as likely to be admitted to ITU than people with pneumonia who did not have a diagnosis of schizophrenia.

“Therefore the findings of this study, where people with schizophrenia and COVID-19 were more likely to die than the general population and people with other mental illness such as mood and anxiety disorders, are plausible.

“The authors of this study were able to control for a number of factors that may have been associated with this increase mortality risk, such as smoking, heart disease and race.

“It should be borne in mind that the findings are based on data from 75 people with schizophrenia and CO-VID 19, and therefore though plausible, should be interpreted cautiously.

“The authors talk about immune function being compromised, and whilst that may well be the case (and there is a small level of increased risk from genetic studies to support this), there are a myriad of factors that could be at play here, including barriers to accessing care early, and perhaps an interplay between these social factors and vulnerability in this population of people.

“In my opinion this study has practical implications-these are a vulnerable group of people, and should be targeted for vaccines, in much the same way as other people at increased mortality risk from CO-VID 19. Parity for people with severe mental illness has been a slogan for a number of years, and the findings from this study underline this.”

Prof Terrie Moffitt FMedSci, Institute of Psychology, Psychiatry and Neuroscience, King’s College London, said:

“I advise readers to approach this publication with caution. The number of patients with schizophrenia in the study was very small. The group of schizophrenia patients studied is likely biased and does not represent people living with schizophrenia  in the population, because the studied patients had access to hospital care, which can be unusual in a country that lacks a national health system.”

Prof Paola Dazzan, Professor of Neurobiology of Psychosis, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, said:

“This study reports important findings on the increased risk of mortality for COVID-19 in patients with a diagnosis of schizophrenia spectrum disorders, in contrast with no increase in risk in individuals with other psychiatric diagnoses. Although a general higher risk of mortality is widely known for individuals with schizophrenia, a key finding of this paper is that the higher risk of mortality from COVID-19 is present even when other medical problems are taken into account.

“Although the sample is relatively small (n=75), the findings are significant in pointing to factors other than comorbidities that could increase the risk, and one is of course the role of the immune system, which the authors also discuss in the paper. While it is unclear whether immune alterations are related to socio-environmental stressors or biological vulnerability to the illness, they may well play a crucial role in the response to COVID-19, given that mortality from this infection has been closely linked with individual immune response.”

Prof David Owens, Professor Emeritus of Clinical Psychiatry, University of Edinburgh, said:

“Interesting and important study – but one whose title reveals the narrow interpretation the authors present in their discussion.

“The study does NOT show that ‘schizophrenia’ increases mortality risk, but that a ‘schizophrenia (spectrum) diagnosis’ carries such a risk.  Although well controlled for an epidemiological investigation, the study does not account for the wide range of social, cognitive and behavioural disadvantages such a diagnosis usually infers. While it is important to consider biological predispositions inherent to the condition, it is surprising that the authors glance over the fact that their work may, again, be illustrating the health and social inequalities to which patients with long-term psychiatric disorders such as schizophrenia remain prone”.

Prof Matthew Hotopf, Vice Dean of Research at the Institute of Psychiatry Psychology and Neuroscience, King’s College London, said:

“The study looked reasonably robust to me; obvious limitations of using health record data, but many advantages too as they can reflect the whole population.

“The number with schizophrenia is not huge, but the overall sample size is good – and though the confidence intervals are fairly wide it’s unlikely to be a chance finding.

“You can’t say that they have adjusted for all the contextual factors which might influence this – they haven’t controlled for obesity, socio-economic status or marital status – and the latter may be really important – such as having a partner who calls 999 when you’re sick. 

“That’s not to say there isn’t a biological mechanism but they have in no way ruled out a social/life-style/co-morbidity mechanism, and these are more likely.

“That said, what matters more is they have identified people with severe mental disorders as a high risk group and this has immediate public health implications regarding vaccination – that’s the important message of the paper.

“Schizophrenia and other severe psychiatric disorders are risk factors for mortality in the general population before COVID.  This is a group with a 10-20 year reduction in life expectancy – more than for many diseases we associated with early death.  The reasons for this are multi-factorial including social deprivation, life-style factors (people with schizophrenia smoke more and have high rates of obesity), harms associated with some medications used to treat psychosis and differential access to healthcare.

“In COVID we know that deprivation is associated with a much higher mortality, so we would therefore expect that people with severe mental illness will be particularly disadvantaged.  In US healthcare system where this study was done, we might also anticipate significant differences in access to healthcare for people with schizophrenia.

“This indicates it is vital that people with schizophrenia are seen as high risk group and have early access to vaccines.”

Prof Celso Arango, past president of the European College of Neuropsychopharmacology, and Director of the Institute of Psychiatry and Mental Health at Hospital Gregorio Marañón in Madrid, said:

“We know that patients with schizophrenia have a life expectancy 20 years lower than the general population. This is due to many reasons, including suicide and comorbidities with other medical disorders, poorer nutrition, less physical exercise, higher incidence of tobacco and illicit drug use, medications side effects, etc. Some of those comorbid conditions were controlled for, but not all of them. Therefore the high mortality in this study may be explained by other comorbid conditions.

“In addition, patients with schizophrenia are well known for being more reluctant to ask for help and have access to medical services, probably even more so in a time where it was extremely difficult to reach available health services, therefore it could be the case that the sample is biased with more severe patients that are admitted or tested later in the course of the disorder with a poorer prognosis.  It may also be the case that their paranoid symptomatology many have caused a distrust of asking for help and their cognitive impairments made it more difficult to solve the barriers present at the peak of the pandemic when the study took place.

“As with any other crisis, the gaps between those more prepared and those more vulnerable will increase and this global crisis will increase the gap between people with and without mental disorders.  Now more than ever, we need to put in place service provision that targets health needs and reduces the actual disparities and those to come.”

Prof Paul Harrison, Professor of Psychiatry, University of Oxford, said:

“The study was reasonably large, and carefully conducted and reported, so we should take the findings seriously.

“The study suggests that psychiatric illness, particularly schizophrenia, is associated with a greater risk of dying from COVID-19. The question is why.  As the authors discuss, there could be a direct connection related to the biology of schizophrenia and COVID-19. Or it could be an indirect relationship due to factors like obesity, general fitness, health behaviours, or even medication. We urgently need research to  find the explanation, as it may be possible to intervene to reduce the risk.”

Dr Tom Pollak, NIHR Clinical Lecturer, King’s College London, said:

“We have known for some time that patients with serious mental illness have poorer physical health outcomes, and more recently that patients with psychiatric diagnoses appear to be at greater risk of poor COVID-19 outcomes. This study is the first to specifically highlight schizophrenia-spectrum disorders as being particularly at-risk. This is an alarming finding: these patients are already amongst the most vulnerable members of society and are probably underserved by most healthcare systems worldwide. The authors included a relatively large number of demographically diverse patients and attempt to control for as many potentially relevant confounding factors such as age, ethnicity and medical history as is possible.

“Recent large-scale studies have suggested that someone’s genetic risk for schizophrenia probably does not increase the risk of getting infections, but it is still an open question as to whether other biological processes, such as acquired problems with the immune system, could predispose to both the development of psychotic disorders and a vulnerability to severe viral infections. Other possible factors that could not be adequately addressed by the design of this study include inequalities in healthcare access and utilisation in this patient group, or whether there was any potential contribution of specific medications used in treating this group.

“Although these findings  need urgent replication in larger samples, there are clear reasons for policy-makers to take notice now, including giving immediate consideration for prioritisation of patients with serious mental illness in nationwide COVID-19 vaccination programmes.”

Prof David Curtis, Honorary Professor, UCL Genetics Institute, said:

“Although it is well recognised that people with severe mental illness are at significantly higher risk of physical ill health, it is very difficult to draw firm conclusions from this study.

“It reports that out of 75 patients with a history of schizophrenia spectrum illness who tested positive for COVID-19, 20 unfortunately went on to die. This seems like a very high rate but in fact the overall mortality for everybody who tested positive was 11.8% which is much, much higher than we would expect for cases in general. The study was carried out in New York between March and May 2020 and it is obvious that the cases included must have been already exceptionally severe for the mortality to be so high. So the study does not really reflect people who have COVID-19 in general but people who managed to get tested by the New York University Health System in the early period of the pandemic.

“The results are based on a small number of patients and there are other reasons to be cautious about the interpretation of this study. I am sure that people with severe mental illness are at higher risk from COVID-19 for a variety of reasons but I do not think this is telling us something exceptional about schizophrenia.”

Prof Shon Lewis, Professor of Adult Psychiatry, University of Manchester, said:

“It is a good, robust study with important findings.  We have known for some time that people with schizophrenia in the UK have a life expectancy reduced by 18-20 years compared to the general population. This awful statistic is due largely to increased rates of cardiovascular, respiratory and metabolic disease resulting from lack of exercise, obesity, smoking and side effects of some medications in people with schizophrenia.

“This latest finding spotlights how good preventive care must now be urgently focused on this incredibly vulnerable and disadvantaged population. They should be immediately prioritised for vaccination.”

‘Association of Psychiatric Disorders With Mortality Among Patients With COVID-19’ by Katlyn Nemani et al. was published in JAMA Psychiatry at 4pm UK TIME on Wednesday 27 January 2021.

doi:10.1001/jamapsychiatry.2020.4442

Declared interests

Prof Curtis: “I have no conflict of interest.”

Dr Arango: “has been a consultant to or has received honoraria or grants from Acadia, Angelini, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda.   

Prof Harrison: “None.”

Dr Pollak: “I have no conflicts of interest.”

Prof Moffitt: “No conflicts of interest.”

Prof Dazzan: “I confirm I have no conflict.”

None others received.