Cognitive symptoms associated with COVID‐19: neuropsychological and biochemical characterization

Background Despite previous studies establishing cognitive impairment as a major complaint in post‐acute COVID‐19 syndrome (PACS), a deeper understanding of the neuropsychological features and underlying causes is needed. We aimed to characterize the cognitive profile of patients affected with cognitive PACS and the influence of biological and psychological factors. Method We performed a prospective single‐center study. We included participants with confirmed SARS‐CoV‐2 infection and long‐term symptoms ≥ 8 weeks after onset who were referred to our unit because of cognitive complaints. All participants completed a comprehensive neuropsychological battery (NPS) and questionnaires assessing depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), apathy (Starkstein Apathy Scale) and fatigue (Multidimensional Fatigue Inventory) at baseline and +1, +3 and +6 months. We collected blood samples and cerebrospinal fluid (CSF) to obtain biochemical and immunological profiles. Group comparisons, correlations and Principal component analysis (PCA) were performed. Longitudinal analyses are ongoing. Result Forty‐nine participants were included (79.6% female, mean age 50.1 (SD 7.9). At the time of assessment, they presented multiple symptoms other than cognitive complaints (88% fatigue, 61% headache, 63% dyspnea, and 10% fever). The NPS showed that executive functions were the most affected (up to 29% of the sample had at least one test altered), followed by memory (at least one test altered in 25%) (Figure 1). On the contrary, language and praxis were preserved. Participants presented with anxiety symptoms (minimal 8.7%, mild in 34.8%, moderate 26.1%, severe 30.4%), depressive symptoms (none 34.8%, mild 26.1%, borderline clinical depression 23.9%, moderate 8.7%, severe 6.5%), and clinically relevant apathy in 64.4%. The sample presented a mean score of total fatigue of 58 (min 48, max 68), (scores 20‐100). Fever and or moderate/severe anxiety were associated with lower scores in some memory and executive functions subtests (Figure 2). Most of the variability in the sample was explained by executive functions subtests (PCA, Figure 3). Patients presented increased levels of interleukins (IL) IL‐1b, IL‐17a and IL‐18 in CSF compared to controls. Conclusion Cognitive PACS predominantly affected executive functions and memory. Fever and moderate/severe anxiety were associated with worse cognitive outcomes. Several inflammatory markers were altered in cogniti