Immune response and cognitive impairment in Post Covid Syndrome

Cognitive difficulties are very frequently reported by people with Post Covid Syndrome (PCS), but there is limited understanding of the underpinning mechanisms leading to these changes. It is possible that cognitive difficulties are related to immune status and/or low mood. The aim of this thesis was to examine the relationship between immune status and cognitive functioning in PCS, while considering whether depression symptoms also influence this association. Study 1 aimed to systematically review the literature examining the relationship between immune status and cognitive difficulties in PCS, as well as evaluate if depression impacts on this relationship. Of 762 articles retrieved from four databases, twelve studies met criteria for our review. Most studies described affected domains of cognition in PCS, with four studies specifically assessing the relationship between immune status and cognition. Three studies presented results indicating an association between elevated immune response and cognitive difficulties. Similarly, three studies suggested an association between mood and cognitive difficulties. No studies included in this review assessed an association between immune status, cognitive functioning and mood concurrently. This review highlights the frequency of cognitive difficulties after COVID-19 infection, and explores predictors of this change in cognitive function. However, we were unable to establish whether immune status is an independent predictor of cognitive function, or whether this association is influenced by mood. Study 2 aimed to examine the relationship between immune status and cognitive functioning in PCS, while considering whether depression symptoms also influence this association. Participants were recruited from an online study of cognitive and psychological consequences of PCS, involving individuals attending a post-COVID service in an acute general hospital, and a comparison sample of age and gender matched community controls who had also been infected with COVID-19, but do not report PCS symptoms. Participants with PCS (n=71) and community controls (n=51) completed the Immune Status Questionnaire (ISQ), Cognitive Failures Questionnaire (CFQ), Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F). Significant differences were observed between groups in terms of immune status, cognitive function, depression, fatigue, with the ‘PCS’ group demonstrating lower immune status, more cognitive difficulties, and higher levels of depression and fatigue. Regression analysis in the PCS group only indicated that immune status and depression significantly contributed to variance in subjective cognitive functioning, with immune status remaining a significant predictor of cognitive functioning scores even when accounting for depression, fatigue and other covariates related to PCS, such as BMI. Our findings suggest that cognitive functioning is influenced by immune status in PCS, emphasising the importance of immune status, cognitive, and mood screening as part of routine clinical care.
The current findings support the need for further study of the relationship between immune status, cognition and depression in PCS, to explore if inflammation impacts on brain function leading to both depression and cognitive symptoms. This could help to uncover underlying mechanisms contributing to PCS, so that interventions are best tailored to improve quality of life for those with cognitive difficulties. Findings from this thesis have the potential to guide better psychoeducation, formal and informal supports, and resilience building for people with PCS.