Immune Response and Cognitive Impairment in Post-COVID Syndrome: A Systematic Review

Background: Altered immune response and cognitive difficulties have been demonstrated in studies of post-COVID syndrome, including differences in immune status and cognitive functioning in the months following infection. This review aimed to examine immune status and cognitive differences in post-COVID syndrome 12 or more weeks after COVID-19 infection. A further aim of this review was to explore a link between immune response and the cognitive deficits observed in this group. Methods: A systematic review was carried out using PubMed, PsychInfo, EMBASE, and Web of Science electronic databases of observational studies 12+ weeks after COVID-19 infection, with assessment of immune status and cognitive function in post-COVID syndrome samples. This review protocol was recorded on PROSPERO with registration number CRD42022366920. Results: Following eligibility screening, 11 studies met inclusion criteria and were selected for our review. Six of eight studies that examined between-group differences in specific domains suggested impaired cognition in the post-COVID syndrome population, with the domain of executive function particularly affected. Of 11 studies with immune data, 7 studies reported increased markers of inflammation in the post-COVID syndrome group, when compared with an age- and sex-matched “healthy control” sample, or population norms. Finally, when immune function and cognition are examined together, 6 studies presented results indicating a significant association between elevated immune response and cognitive function in post-COVID syndrome. Conclusion: This review highlights the frequency of cognitive difficulties months after COVID-19 infection and explores heightened immune response as a predictor of this change. Six studies suggest that immune status is a predictor of cognitive function, examining a marker of immune function and objective cognitive performance at 12 or more weeks following infection. Future studies of cognitive function in post-COVID syndrome are needed to explore this relationship and underlying mechanisms leading to changes in cognitive performance.