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

Abstract

Background Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients. Methods We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms. Results The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2. Conclusions and relevance Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources. Trial registration NA.

Pattern of cognitive deficits in severe COVID-19

“…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 longterm follow-up whether patients will completely recover.…”

“…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.…”

Psychological and neuropsychiatric implications of COVID-19

“…The incidence of delirium in COVID-19 has been reported to range from 9 [51] to 14.8% [40], which is 1.5-twofold lower than the prevalence rate reported in two recent systematic reviews and meta-analyses for adults either treated in an intensive care unit (ICU) in general [58], or due to COVID-19 infection (64% [18]) on neurology wards (27% [59]) or those requiring end-of-life care/symptom control (24% [60]). Similarly, a bicentre French study reported very high incidence of delirium in their severely ill COVID-19 patents in the ICU [118/140 (84.3%)], with 88 patients (69.3%) exhibiting hyperactive delirium, despite high infusion rates of sedative treatments and neuroleptics [61]. The Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%).…”

“…Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient [61].…”

Would Repurposing Minocycline Alleviate Neurologic Manifestations of COVID-19?

“…Elevated IL-6 and abnormal permeability of blood meningeal barrier associated with encephalopathy was identified in another cohort with 140 patients admitted to ICU with COVID-19 diagnosis. Eighty-four percent showed abnormal neurological examination and/or delirium with significant worse prognosis compared to patients without delirium and normal neurological exam (Helms et al, 2020b). It might be explained by the intense systemic inflammatory response that leads to blood-brain barrier leakage and higher permeability to peripheral cytokines that exacerbate neuroinflammation and consequently, neurological damage (Cain et al, 2019).…”