Evidence for a severe cognitive subgroup in a comprehensive neuropsychological Post-COVID-19 syndrome classification

Approximately 7% of adults develop Post-COVID-19 syndrome (PCS). Cognitive impairment is common, but its profile in PCS is not well defined and requires clearer differentiation from general (post-)illness effects. The aim of this study was to identify distinct cognitive profiles in PCS and to characterize them with respect to broader psychological factors such as fatigue, depression, anxiety, and personality. To this end, we assessed cognition, fatigue, depression, anxiety, and personality traits in PCS patients, convalescents (CV), healthy controls (HC), and post-viral syndrome patients (PV) of different etiology. Cognitive performance was assessed with an extensive protocol covering multiple cognitive domains, including verbal and nonverbal short-term memory, verbal and nonverbal working memory, verbal and nonverbal episodic memory, visuoconstruction, attentional functions, and executive functions, alongside patient-reported measures of fatigue, depression, anxiety, and personality, as well as self-reported information on lifetime psychiatric diagnoses. Group comparisons and discriminant analysis (p = .065) identified the tests that best differentiate the groups, while exploratory cluster analysis allowed for data-driven group assignment. In this study, N = 54 PCS, N = 42 HC, N = 25 CV, and N = 12 PV were included. Patients with PCS show low mean scores and cluster into two subgroups: 7.5% with severe objective cognitive impairments (PCS_SCI) and 92.5% with cognitive performance comparable to CV, HC, and PV (Mixed_(non-SCI)). The PCS_SCI subgroup showed pronounced objective impairments, particularly in attentional, memory, and executive domains. Across the entire PCS sample, objective cognitive impairments were not predicted by fatigue severity or affective state (depression or anxiety), although lifetime psychiatric disorders and cognitive fatigue were significantly more prevalent in PCS_SCI. Among patients with PCS, a distinct subgroup of individuals presents with severe cognitive deficits, significant cognitive fatigue, and an increased lifetime vulnerability for psychiatric disorders, highlighting the need for targeted diagnostic assessments and personalized (psycho-)therapeutic interventions.