The aging whole blood transcriptome reveals a potential role of FASLG in COVID-19

Abstract The risk for severe COVID-19 increases with age as older patients are at the highest risk. Identifying how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacts with blood components during aging is urgent. We investigated the aging whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins interacting with viral proteins. From 22 DEGs in aged blood, FASLG, CTSW, CTSE, VCAM1, and BAG3 changed their expression with involvement in immune response, inflammation, cell component and adhesion, and platelet activation/aggregation. Males and females older than 50 overexpress FASLG possibly inducing a hyper-inflammatory cascade. The expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 was increased throughout aging in both gender. By exploring publicly available Single-Cell RNA-Sequencing data on peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed in natural killer cells and CD8 + T lymphocytes, whereas BAG3 was expressed in CD4 + T cells, naive T cells, and CD14 + monocytes. The expression of FASLG in aged blood may explain why older patients are more prone to viral infection complications. The results indicate FASLG as a prognostic candidate and potential therapeutic target for the more aggressive clinical manifestation of COVID-19. The reduction of FASLG could be helpul against disease progression.