Avaliação de marcadores inflamatórios periféricos em pacientes com sintomas cognitivos pós-COVID-19

Abstract

Long COVID is frequently associated with the persistence of cognitive symptoms; however, the biological mechanisms involved have not yet been fully elucidated. This study aimed to investigate the association between peripheral plasma cytokines and cognitive performance in individuals with long neuroCOVID, as well as to assess the discriminatory potential of these biomarkers. This was a cross-sectional observational study comprising 46 participants: 22 individuals with a history of SARS-CoV-2 infection confirmed by PCR and persistent cognitive symptoms in the post-COVID-19 period, and 24 controls without a history of COVID-19. Participants were recruited through public dissemination of the study and underwent a comprehensive neuropsychological assessment to investigate and objectively confirm cognitive impairments, including tests of attention, memory, processing speed, executive functions, language, and functionality, in addition to plasma measurement of the cytokines IL-1β, IL-4, IL-6, IL-10, IL-18, and TNF by ELISA. Between-group comparisons, correlation analyses, linear regression, and ROC curves were used to investigate the relationship between the molecules and cognitive performance. The results showed greater impairment in executive functions, attentional processes, and the retrieval of long-term verbal episodic memory, whereas language, abstract reasoning, and global functionality remained preserved. Plasma levels of TNF, IL-10, and IL-18 were significantly reduced in the long neuroCOVID group, whereas IL-4 and IL-6 did not differ between groups, and IL-1β was not detected. IL-18 showed a marked alteration in the organization of the cytokine correlation network and, after adjustment for time since infection and depressive symptoms, was positively associated with immediate verbal memory performance. In addition, IL-18 showed exceptional discriminatory capacity for distinguishing individuals with long neuroCOVID from controls (AUC = 0.94). It is concluded that cognitive impairment in long neuroCOVID is associated with alterations in the plasma cytokine profile. In this context, the findings reinforce the potential of IL-18 as a promising biomarker of long neuroCOVID, given its alterations in the organization of the inflammatory network, its association with cognitive performance, and its excellent discriminatory capacity between groups, contributing to the understanding of the underlying pathophysiological mechanisms and to future investigations into its clinical application, although longitudinal studies with larger sample sizes are needed.