Characterising neuropsychiatric disorders in patients with COVID-19

We 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.

The absence of delirium in the Article's case definitions is troubling and imposes considerable constraints on the interpretation of this study, because delirium is likely to be the most frequent neuropsychiatric complication of COVID-19.² Consistent with the high prevalence of delirium in most serious, acute diseases, we expect delirium to be present in at least a quarter of older patients (aged ≥65 years) with COVID-19 and more than two-thirds of severe cases. However, most reports have used non-standard terminology to describe the mental status phenotypes in COVID-19 (eg, dysexecutive syndrome, confusion, altered consciousness, or altered mental status). Of note, confusion was the fifth most common presenting feature of COVID-19 overall in the International Severe Acute Respiratory and Emerging Infection Consortium WHO study (n=20 133).²

In Varatharaj and colleagues' study,¹ altered mental status is defined as “an acute alteration in personality, behaviour, cognition, or consciousness”. Additional, undefined terms include unspecified encephalopathy, new-onset psychosis, and neurocognitive (dementia-like) syndrome. Presuming acute onset, most of these cases probably would have fulfilled DSM-5 criteria for delirium. The authors do acknowledge a potential reporting bias, but we suggest that a broader approach to reporting of cases, for example by geriatricians and acute physicians, would have generated a more representative sample.

The issue of the damaging consequences of inconsistent terminology was the subject of a position statement, published in February, 2020, on the preferred nomenclature of delirium and acute encephalopathy, endorsed by ten professional societies.³ The position statement advocates that all disciplines adopt a shared approach to classification and nomenclature. There are sound reasons for identifying delirium in particular; unlike altered mental status and other imprecise terms, delirium is a valid, operationalised diagnostic construct with high reliability and strong utility (panel ).³ A diagnosis of delirium compels a standardised approach to management and, crucially, facilitates communication with patients and carers, which is essential for alleviating their distress. We urge consistency of nomenclature as presented in this recent statement.

Panel. Value of identifying delirium.

Validity

• •Risk factors identifiable
• •High construct validity
• •Its prevalence and severity predict serious outcomes (eg, hospital costs, morbidity, mortality)

Reliability

• •Clear, operationalised criteria
• •Facilitates systematic screening
• •Clinical instruments widely available

Utility

• •Prioritises prevention
• •Common presenting feature of serious systemic illness
• •Directs clinicians to guidelines and treatment pathways
• •Draws attention to possible psychological distress
• •Encourages vigilance for problematic behavioural features
• •Facilitates communication with patients and carers
• •Facilitates accurate coding
• •Strong association with dementia and cognitive decline

The current unresolved tension between delirium and acute encephalopathy is more than word-deep and calls for a unified approach to the clinical syndrome and its underlying neuropathophysiology. According to the recent position statement, delirium describes a discrete clinical syndrome and acute encephalopathy describes the neuropathophysiology.³ Of note, animal models substantiate this approach. For example, peripheral inflammation in such models has been shown to provoke both a delirium-like syndrome and new neurophysiological changes in the brain.⁴ The term delirium disorder aims to integrate the two previous terms and the models they represent.⁵ We propose that it is inadequate to use the term delirium without specifying the underlying cause or putative neuropathophysiology, or to use the term acute encephalopathy without consistently characterising the mental status phenotype.