Subtle cognitive impairments in memory, attention, and executive functioning in patients with post-COVID syndrome and their relationships with clinical variables and subjective complaints

Background and objectives Cognitive symptoms persisting beyond three months following COVID-19 present a considerable disease burden. We aimed to establish a domain-specific cognitive profile of post-COVID syndrome (PCS) and relationships with subjective cognitive complaints and clinical variables to provide relevant information for the understanding of cognitive dysfunction and its predictors in a clinical cohort with PCS. Methods In this cross-sectional study, we compared cognitive performance on the clinically viable Oxford Cognitive Screen-Plus between a large post-COVID cohort ( n = 282) and a socio-demographically matched healthy control group ( n = 52). We assessed group differences in terms of fatigue and depression as well as relationships between cognitive dysfunction and clinical and patient-reported outcomes. Results On a group-level, patients scored significantly lower on delayed verbal memory (non-parametric effect size r = .13), attention ( r = .1), and executive functioning ( r =.1) than healthy controls. In each of these domains, 10-20% of patients performed more than 1.5 SD below the healthy control mean. Delayed Memory was particularly affected and a small proportion of its variance was explained by hospitalisation ( β = -.72, p < .01) and age ( β = -.03, p < .05; R2adj. = .08). Attention scores were significantly predicted by hospitalisation ( β = -.78, p < .01) and fatigue ( β = -.04, p < .05; R2adj. = .06). Discussion PCS is associated with long-term cognitive dysfunction, particularly in delayed verbal memory, attention, and executive functioning. Deficits in delayed memory performance seem to be of particular relevance to patients’ subjective experience of impairment. Initial disease severity, current level of fatigue, and age seem to predict cognitive performance, while time since infection, depression, and pre-existing conditions do not. Longitudinal data are needed to map long-term course of cognitive dysfunction in PCS. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The post-COVID Centre was supported by the Thueringer Aufbaubank (2021 FGI 0060). This work was further supported by funds to KF from the German Forschungsgemeinschaft [DFG, FI 1424/2-1] and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, identifier H2020-MSCA-ITN-2019-859890). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics committee of the Friedrich-Schiller-University gave ethical approval for this study [amendment to 5082-02/17]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.