Neuropsychological functioning in post-ICU patients after severe COVID-19 infection: The role of cognitive reserve

BACKGROUND: Cognitive manifestations associated with Severe Acute Respiratory Syndrome by Coronavirus 2 (SARS-CoV-2) are yet to be described in the existing literature. The aim of this exploratory study is to analyze the impact of severe SARS-CoV-2 infection on neuropsychological performance 6 months following hospital discharge, and to identify which medical variables predict worse outcome. In this context, we study if cognitive reserve (CR) may play a protective role on cognitive impairment. METHODS: We enrolled a cohort of 102 severe SARS-CoV-2 survivors who had been admitted to the Intensive Care Unit (ICU) and were contacted 6-months post discharge. A total of 58 agreed to participate in this 6-month follow-up study. Patients with previously known cognitive impairment were excluded. Demographic, clinical and laboratory data were collected. Firstly, to test the magnitude of neurocognitive sequalae two standard deviations below normative group were considered. Secondly, to analyze the main effects of medical variables on cognition and the interaction with cognitive reserve, ANCOVA analyses were performed. RESULTS: 53.4% obtained a score below the cutoff point (<26) in the screening test MOCA. ICU variables including mechanical ventilation, days of sedation or high CRP days were related with cognition. Cognitive Reserve (CR) interacted with delirium (F ​= ​6.8, p ​= ​0.01) and sedation days (F ​= ​9.40, p ​= ​0.003) to predict verbal memory and interacted with high CRP to predict phonemic fluency (F ​= ​6.47, p ​= ​0.01). Finally, no differences in neuropsychological performance were found depending on subjective cognitive impairment (SCI). However, patients with SCI had a higher score in the HAD anxiety subscale (t ​= ​−2.2; p ​< ​0.05). CONCLUSIONS: In our cohort, cognitive dysfunction was related with ICU variables such as delirium, mechanical ventilation, and inflammation. CR modulated the impact of these variables on cognition. Cognitive complaints were related with anxiety but not with cognitive performance. Despite some limitations, including the need of replication of the findings with larger samples and control groups, our study suggests that high CR may be protective for severe COVID-19-related cognitive impairment.