key: cord-0855072-oshsna6g
authors: Beaud, Valérie; Crottaz-Herbette, Sonia; Dunet, Vincent; Vaucher, Julien; Bernard-Valnet, Raphaël; Du Pasquier, Renaud; Bart, Pierre-Alexandre; Clarke, Stephanie
title: Pattern of cognitive deficits in severe COVID-19
date: 2020-11-20
journal: J Neurol Neurosurg Psychiatry
DOI: 10.1136/jnnp-2020-325173
sha: 4cf9d9c53bf27fa2416c2a45b1f9dcccdc2ea9c3
doc_id: 855072
cord_uid: oshsna6g

nan

The severe form of COVID-19 tends to be associated with neurological deficits. 1 2 Among patients with acute respiratory distress syndrome (ARDS), who benefited from mechanical ventilation and were examined after discontinuation of sedation and neuromuscular blockade, 69% presented agitation, 65% confusion, 67% corticospinal tract signs and 33% dysexecutive syndrome. 2 We describe here the pattern of cognitive deficits in a series of 13 consecutive inpatients hospitalised in the Lausanne University Hospital, whom we examined during the post-critical acute stage of severe COVID-19 (table 1) . Inclusion criteria were COVID-19 diagnosed by PCR and ARDS that required intubation and mechanical ventilation in intensive care unit (ICU). Exclusion criteria were prior psychiatric or neurological diseases, including neurocognitive impairment or dementia. At the time of testing, patients were no longer sedated and ICU delirium symptoms, which were present in seven patients, resolved in six of them (P5-P7, P10, P11, P13) or subsided to a great extent (P12).

The neuropsychological evaluation comprised two standardised test batteries. (table 1) ; its occurrence was correlated with MoCA score (rho=−0.619; p=0.024) and cognitive slowness (rho=0.585; p=0.036), but not with FAB, length of ICU stay, duration of mechanical ventilation, delay between ICU discharge and cognitive assessment, age, gender, mental fatigue, mood and anxiety disturbances.

Eleven patients had brain imaging. None of them sustained acute stroke or ischaemic damage; among the eight patients who had MRI-based morphometry, focal brain atrophy was, however, present in patients with normal (table 1; P1) or deficient performance at MoCA (P10-P13) as it was absent in patients with normal (P3, P4) or deficient performance at MoCA (P7). Four patients had lumbar puncture, revealing enhanced proteinorachia (P3, P11, P13) and barrier index (P11, P13) or normal values (P12).

Two cognitive profiles characterise the post-critical acute phase of severe COVID-19: (1) normal score at MoCA, but tendency for lower performances PostScript in executive than in other cognitive functions; (2) mild to severe deficits at MoCA with extensive cognitive impairment in executive, memory, attentional and visuospatial functions, but relatively preserved orientation and language, executive dysfunction being confirmed by the FAB score. These cognitive profiles together with mood and anxiety disturbances, which we observed in the acute stage, in the absence of stroke, are reminiscent of those reported in the aftermath of ARDS of other aetiologies, where up to 70% of ARDS survivors had presented at hospital discharge cognitive deficits, affecting predominantly attention, mental processing speed, memory and executive functions, 3-5 with a high prevalence of depression and anxiety. 5 Furthermore, cognitive impairment in severe COVID-19, as in ARDS of other aetiologies, 5 does not correlate with length of mechanical ventilation or length of ICU stay and thus severity of the acute illness. However, the occurrence of ICU delirium tends to be associated with poorer cognitive performance. 1 Structural damage, such as ischaemic or hypoxemic lesions of the hippocampus, basal ganglia or cerebellum lesions as well as brain atrophy (in particular hippocampal) or disruption of functional connectivity, which occur frequently in ARDS survivors, 3 4 may contribute to cognitive dysfunction. In the context of COVID-19, stroke and perfusion abnormalities have been reported, 1 2 but were excluded here in all 11 patients, who had brain imaging during the acute stage. Prior brain atrophy may confer worse outcome as shown for the risk to develop delirium and cognitive disorders in ARDS of other aetiologies. 3 4 Patchy grey and/or white matter atrophy was present in five patients (of the eight who had MRI), most likely reflecting a prior condition; it was associated with cognitive impairment in four patients. However, brain atrophy did not always induce cognitive impairment and conversely, cognitive impairment was also present without imaging abnormalities, as in previous non-COVID-19 studies. 4 Our sparse data on cerebrospinal fluid suggest that increased blood-brain barrier permeability may contribute to neurological symptoms, as previously described for mild central nervous system inflammation in ICU patients. 1 In conclusion, pattern of cognitive deficits, present during the acute stage in our 13 patients without history of cognitive, psychiatric or neurological disorders, is probably linked to critical illness as part of ARDS due to COVID-19, since it is very similar to those reported in ARDS of other aetiologies. Further investigations are needed to determine predictive factors and underlying neural mechanisms, and clarify with a long-term follow-up whether patients will completely recover.

Delirium and encephalopathy in severe COVID-19: a cohort analysis of ICU patients

Neurologic features in severe SARS-CoV-2 infection

Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions

Brain atrophy and cognitive impairment in survivors of acute respiratory distress syndrome

Two-Year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome

Patient consent for publication Not required.

The procedure was approved by the Cantonal Ethics Committee of Vaud and informed consent was obtained in agreement with the requirements of the Ethics Committee.Provenance and peer review Not commissioned; externally peer reviewed.

Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http:// creativecommons. org/ licenses/ by-nc/ 4. 0/.