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

Abstract

The risk for severe illness from COVID-19 increases with age as older patients are at the highest risk. Although it is still unclear whether the virus is blood-transmitted, the viral RNA is detected in serum. Identifying how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) interacts with specific blood components during aging is expected to guide proper therapies. Considering that all human coronavirus require host cellular molecules to promote infection, we investigated the aging whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins potentially interacting with viral proteins. From a total of 22 DEGs in aged blood, five genes (FASLG, CTSW, CTSE, VCAM1, and BAG3) changed expression during aging. These age-related genes are involved in immune response, inflammation, cell component and cell adhesion, and platelet activation/aggregation. Both males and females older than 50 overexpress FASLG compared with younger adults (20-30 years old), possibly inducing a hyper-inflammatory cascade that activates specific immune cells. Furthermore, the expression of cathepsins (CTSW and CTSE) and the anti-apoptotic co-chaperone molecule BAG3 was significantly increased throughout aging in both gender. By exploring publicly available Single-Cell RNA-Sequencing (scRNA-Seq) data on peripheral blood of SARS-CoV-2-infected patients, we found FASLG and CTSW expressed mainly in natural killer (NK) cells and CD8+ (cytotoxic) T lymphocytes whereas BAG3 was expressed in CD4+ T cells, naive T cells, and CD14+ monocytes. The increased expression of FASLG in blood during aging may explain why older patients are more prone to severe acute viral infection complications. These results indicate FASLG as a prognostic candidate and potential therapeutic target for more aggressive clinical manifestation of COVID-19.

Epigenetic modifications associated with genes implicated in cytokine storm: The potential biotherapeutic effects of vitamins and minerals in COVID‐19

“…Similarly, FASLG gene expression in the blood has been linked to severe acute viral infection consequences in older people. As the FASLG gene is found in older adults and majorly expressed by the T lymphocytes and the natural killer, it may cause a hyper-inflammatory cascade that stimulates certain immune cells (Chuffa et al, 2021), perhaps leading to a cytokine storm. Gene ontology analysis of 210 genes that were upregulated in 4 different SARS-CoV-2-infected tissues (normal human bronchial epithelial cells, PBMC, BALF, and COVID-19 postmortem) revealed significant enrichment of host response pathways.…”

“…Similarly, FASLG gene expression in the blood has been linked to severe acute viral infection consequences in older people. As the FASLG gene is found in older adults and majorly expressed by the T lymphocytes and the natural killer, it may cause a hyper‐inflammatory cascade that stimulates certain immune cells (Chuffa et al., 2021), perhaps leading to a cytokine storm.…”

Expression profile analysis of COVID-19 patients

“…They are involved in immune response, inflammation, cellular component and cell adhesion, and platelet activation/aggregation. Moreover, the expression profile changed differently in men and women with aging 3 . In general, the transcriptomic signature of COVID-19 overlaps to a large extent with that of influenza and other acute respiratory infections.…”