Mapping the Potential Genes and Associated Pathways Involved in Long COVID-Associated Brain Fog Using Integrative Bioinformatics and Systems Biology Strategy

One of the recent emerging global health issues is long COVID. Among long COVID patients, long COVID-associated brain fog is an important area. We noted an immense gap in understanding the genes and associated pathways involved in long COVID-associated brain fog. Therefore, the study has been selected to understand the genes and pathways involved in patients with long COVID-associated brain fog. A GEO dataset, which was developed through the RNA-seq, was used for the analysis. The dataset encompasses 22 human samples of PBMC. The dataset (human samples of PBMC) was grouped into four cohorts for this study: healthy cohort, COVID convalescent, long COVID, and long COVID brain fog. Therefore, the selection criteria for the 22 PBMC samples were based on the individual infection type (COVID convalescent, long COVID, and long COVID brain fog) and the healthy cohort. Using DEG profile evaluation, we revealed 250 top-ranked DEGs with P values, Padj, baseMean, etc. From the top-ranked DEGs, we listed 24 significant DEGs and some significant DEGs are SMAD3 (P value = 6.34e-07), PF4 (P value = 1.88e-05), TNFAIP3 (P value = 3.70e-06), CXCL5 (P value = 1.22e-08), etc. Among the top-ranked DEGs, we found some genes linked with different biological functions, such as inflammatory cytokine secretion, inflammation, microclot formation, and BBB disruption. From our investigation, we found some genes that are associated with this condition, namely PF4, SMAD3, CXCL5, TNFAIP3, etc. From the literature survey and functional pathway enrichment analysis, we noted the function of the genes such as PF4, SMAD3, and CXCL5. We found that PF4 assists in clot formation, and SMAD3 is associated with neuroinflammation. Similarly, CXCL5 is an inflammatory marker associated with neuroinflammation and BBB damage. At the same time, the study with functional pathway enrichment analysis reflects that DEGs of long COVID-related brain fog might be associated with several biological pathways and processes, cell signatures, and gene-disease associations. It reflects that the disease is a highly complex one. Our study will provide an understanding of the genes and associated pathways in long COVID-related brain fog, which will assist in the next-generation biomarker discovery and therapeutics for these patients.