Fig. 7

Long-COVID could impact brain functionality through vasculo-proliferative events possibly hosted by the blood–brain barrier. A Heatmaps reflect the levels of the most significant neurological markers per OLINK panels I, II and III, which were largely changed in Long-COVID patient plasma. Values were hierarchically clustered based on Pearson correlation algorithms. For data visualization we used Morpheus software, a tool designed by the Broad Institute. B Table shows functional annotation terms obtained with tools from the Gene Set Enrichment Analysis (GSEA) platform. These clusters refer to leucocyte migration, positive immune signals, glial cell differentiation, neurogenesis and MAPK regulatory pathways. At the right, diagram shows a segment of brain degeneration pathways as described by KEGG charts and processed for protein–protein interaction capacities with STRING software (confirmed by iPathwayGuide). TNF and APP proteins are highlighted as major players. The latter finding suggests that Lecanemab, a humanized IgG1 monoclonal antibody that targets amyloid beta, could be considered as a disease modifying immunotherapy. According to KEGG encyclopedia (target-based classification of drugs chapter), Bepranemab is a humanized, monoclonal antibody that binds to the central region of the Tau protein whose primary role is maintenance of the microtubules in neuronal axons. Bepranemab affects three target pathways in the brain: i) Neurodegeneration, ii) Alzheimer Disease, and MAPK pathways related to cell survival. Taken together, this data is indirectly pointing to a possible blood brain barrier dysfunctionality based on cell proliferation. C The expression levels of markers from the above functional groups have been plotted on graphs, where comparison has been done among all study groups. P-value was considered significant if < 0.05 with ANOVA. One highly expressed biomarker marker was the Amyloid Precursor Protein (APP/Presenilin) that is mainly known as a pathognomonic marker for Alzheimer disease and/or brain inflammation