Executive Function Decline and Its Association With TNF-α in the Later Stages of Post-Acute Sequelae of COVID

Abstract

Beyond the immediate impact of the COVID-19 pandemic, survivors often grapple with incapacitating post-infection symptoms, referred to as Post-Acute Sequelae of COVID (PASC) when persistent beyond 90 days. Cognitive manifestations, encompassing attention, memory, and executive functions (EF), collectively termed brain fog, contribute to functional challenges in PASC. This infection also elicits a long-lasting pro-inflammatory response that persists even after viral clearance, potentially correlated with brain fog. However, it is unclear whether pro-inflammatory responses and cognitive sequelae persist beyond 1 year after the onset of infection. Thus, this study sought to investigate the long-term consequences of PASC on EFs as well as a potential association with markers of inflammation. Forty individuals with PASC who passed performance validity testing (PVT) and 40 matched healthy controls (HC) underwent neuropsychological assessments, including the Montreal Cognitive Assessment to assess global cognition, Victoria Stroop Test to assess inhibitory control, Wisconsin Card Sorting Test to assess cognitive flexibility, Digit Span Task to assess working memory, and Mackworth Clock Test to assess sustained attention on the Psychology Experiment Building Language (PEBL) toolkit. Serum was assayed for tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). Results indicate significant EF decline in PASC, inversely correlated with serum TNF-α concentrations, approximately 562 ± 225 days after the onset of infection. Thus, there exists protracted EF decline in PASC, persistent even beyond 1 year after the onset of infection. Increased levels of TNF-α are observed to be associated with poorer executive functioning in PASC.