Characterising neuropsychiatric disorders in patients with COVID-19 – Authors' reply
Authors: Aravinthan Varatharaj, Thomas A Pollak, Timothy R Nicholson, Jonathan P Coles, Laura A Benjamin, Alan Carson, Rhys H Thomas, Benedict D Michael, Nicholas WS Davies, Gerome Breen, Michael Zandi, Mark A Ellul, Naomi Thomas, Elizabeth L Tenorio, Mustafa Sultan, Ava Easton, Craig Smith, Rachel Kneen, Martin R Turner, Hadi Manji, Tom Solomon, David K Menon, Sarah L Pett, Ian Galea
Journal: The Lancet Psychiatry (2020)

We thank Dorothy Wade and colleagues and Mark Oldham and colleagues for their recognition of the cross-speciality effort of members of the UK's major professional neuroscience bodies who undertook this challenging UK-wide study during the exponential phase of the COVID-19 pandemic.1Varatharaj A Thomas N Ellul MA et al.Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study.Lancet Psychiatry. 2020; (published online June 25.)https://doi.org/10.1016/S2215-0366(20)30287-XSummary Full Text Full Text PDF PubMed Scopus (920) Google Scholar We also welcome the involvement of geriatricians and psychologists in future research. We agree that delirium is common, especially in severe infections and in the intensive care unit. As stated in our Article, we acknowledge that the study might have not recorded all such cases. Changes in mental status with clear and recognised risk factors were not the focus of this study (eg, those explained by severe systemic illness and associated with dementia or cognitive impairment). We agree that if such commonly observed complications were included, they might have substantially increased the number of patients recruited, mirroring the situation in other critical illnesses. In this situation, the burden of CNS complications arising from COVID-19 would be even greater than we found in our study. We agree that consistent terminology is needed for the many causes of alterations of mental state and an improved understanding of the underlying pathophysiology that should determine this is urgently required. We acknowledge the position paper on a proposed terminology of these complex presentations and, appreciating the value of multidisciplinary approaches, would support involvement of the professional bodies in relevant areas of psychiatry, neuropsychiatry, and neurological infection, as well as patient and public involvement, in future iterations.2Slooter AJC Otte WM Devlin JW et al.Updated nomenclature of delirium and acute encephalopathy: statement of ten societies.Intensive Care Med. 2020; 46: 1020-1022Crossref PubMed Scopus (192) Google Scholar We understand the motivations for wishing to avoid the term altered mental status. However, we carefully considered the information notified and took an ontological approach for over-arching terms that include disturbances of mental state occurring without the clinical features of delirium (including isolated psychosis, catatonia, anxiety, and mania). Our study was done with clear a-priori clinical case definitions, such as encephalitis, to support the experienced clinicians reporting cases, reflecting national guidelines, and it was clearly intended to report acute presentations. We took a strong view that the knowledge of the bedside specialist clinician assessing the patient was inherently valuable, and that rediagnosing patients from a distance would be neither wise nor accurate. Psychiatrists, for example, commonly differentiate psychosis from psychotic symptoms occurring as part of delirium; indeed, it is routine practice to provide reassurance that new-onset psychosis is actually delirium and should resolve. Even in 1918, both psychiatrists and neurologists, including Menninger and von Economo,3Menninger KA Psychoses associated with influenza: I. General data: statistical analysis.JAMA. 1919; 72: 235-241Crossref Scopus (77) Google Scholar were careful to distinguish patients with primary brain dysfunction or disease from those whose symptoms were explained by systemic processes. Our study was designed from the outset in a three-stage approach: stage 1 is the core dataset provided by clinicians during the pandemic;1Varatharaj A Thomas N Ellul MA et al.Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study.Lancet Psychiatry. 2020; (published online June 25.)https://doi.org/10.1016/S2215-0366(20)30287-XSummary Full Text Full Text PDF PubMed Scopus (920) Google Scholar stage 2 is detailed clinical data collection; and stage 3 is to evaluate disease mechanisms, including viral neurotropism and para-infectious or post-infectious innate and adaptive immune responses, polygenic risk, endothelial dysfunction, and coagulopathy. Stages 2 and 3 are underway. Substantial evidence exists that non-CNS infection can cause neuropsychiatric presentations in the absence of delirium,4Köhler-Forsberg O Petersen L Gasse C A nationwide study in Denmark of the association between treated infections and the subsequent risk of treated mental disorders in children and adolescents.JAMA Psychiatry. 2019; 76: 271-279Crossref PubMed Scopus (137) Google Scholar which has now been shown with severe acute respiratory syndrome coronavirus 2 infection.5Parra A Juanes A Losada CP et al.Psychotic symptoms in COVID-19 patients. A retrospective descriptive study.Psychiatry Res. 2020; 291113254Crossref PubMed Scopus (120) Google Scholar We therefore strongly disagree that all acute COVID-associated neuropsychiatric phenomenology can be explained by delirium. Full detailed analysis of stage 2 and 3 data from this study is underway and the multidisciplinary authors will continue to be guided by the clinical data and underlying disease mechanisms. Altered mental status will continue to remain an important term in our global WHO and World Federation of Neurology studies of COVID-19 and the brain until these mechanisms are elucidated. We welcome ongoing discussions and collaborations on the intersections of these complex concepts and disorders as this important work progresses. For the guideline from the Faculty of Intensive Care Medicine see https://www.ficm.ac.uk/sites/default/files/ficm_rehab_provisional_guidance.pdf For the guideline from the Faculty of Intensive Care Medicine see https://www.ficm.ac.uk/sites/default/files/ficm_rehab_provisional_guidance.pdf AV is a Medical Research Council (MRC) PhD fellow. JPC received funding from the National Institute for Health Research (NIHR) Cambridge BioMedical Research Centre, during the conduct of the study. LAB reports funding from GlaxoSmithKline and Research England, outside the submitted work. AC reports personal fees from independent testimony in court on a range of neuropsychiatric topics and as a paid editor of the Journal of Neurology, Neurosurgery and Psychiatry, outside the submitted work. Additionally, AC is planning a rehabilitation trial after COVID-19, which could produce an application that might be associated with intellectual property. RHT reports personal fees from Eisai, GW Pharma, Sanofi, UCB Pharma, Zogenix, Bial, and Arvelle, outside the submitted work. RHT has received funding from the Academy of Medical Sciences (AMS) and Wellcome. BDM has received funding from the MRC, AMS, Wellcome, and the NIHR. BDM is supported by the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (IS-HPU-1112-10117) and the NIHR Global Health Research Group on Brain Infections (17/63/110). All other authors declare no competing interests. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance studyTo our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy. Full-Text PDF Characterising neuropsychiatric disorders in patients with COVID-19As a group of senior National Health Service critical care psychologists and consultants, we would like to respond to the Article by Aravinthan Varatharaj and colleagues1 published in The Lancet Psychiatry. We congratulate the authors on conducting the first UK study of neurological and psychiatric complications of COVID-19 in 153 patients. However, we are concerned about the interpretation of the data on altered mental status, found in 37 patients. The authors state that 21 of these patients had new psychiatric diagnoses, including ten with new-onset psychosis, six with a neurocognitive (dementia-like) syndrome, and four with an affective disorder. Full-Text PDF Characterising neuropsychiatric disorders in patients with COVID-19We commend Aravinthan Varatharaj and colleagues1 for their study on neurological and neuropsychiatric complications of COVID-19, and we echo their comments on the importance of interdisciplinary work in the clinical neurosciences. However, we are concerned by their reliance on the vague term altered mental status and the use of the term encephalopathy without reference to delirium. Full-Text PDF