Spatial Mapping of Genes Implicated in SARS-CoV-2 Neuroinvasion to Dorsolateral Prefrontal Cortex Gray Matter

Abstract

Introduction: SARS-CoV-2 is the newest beta coronavirus family member to demonstrate neuroinvasive capability in severe cases of infection. Despite much research activity in the SARS-CoV-2/COVID-19 space, the gene-level biology of this phenomenon remains poorly understood. In the present analysis, we leveraged spatial transcriptomics methodologies to examine relevant gene heterogeneity in tissue retrieved from the human prefrontal cortex. Methods: Expression profiles of genes with established relations to the SARS-CoV-2 neuroinvasion process were spatially resolved in dorsolateral prefrontal cortex tissue (N = 4). Spotplots were generated with mapping to six (6) previously defined gray matter layers. Results: Docking gene BSG, processing gene CTSB, and viral defense gene LY6E demonstrated similar spatial enrichment. Docking gene ACE2 and transmembrane series proteases involved in spike protein processing were lowly expressed across DLPFC samples. Numerous other findings were obtained. Conclusion: Efforts to spatially represent expression levels of key SARS-CoV-2 brain infiltration genes remain paltry to date. Understanding the sobering history of beta coronavirus neuroinvasion represents a weak point in viral research. Here we provide the first efforts to characterize a motley of such genes in the dorsolateral prefrontal cortex.

Sequelae of long COVID, known and unknown: A review of updated information

“…SARS-CoV-2 is a neurotropic virus, and ACE2 plays a role as a docking gene for cellular entry. Along with other genes such as neuropilin-1, basigin (BSG; CD147), and transmembrane protease serine 2 (TMPRSS2), SARS-CoV-2 can enter the brain (102,103). In addition, SARS-CoV-2-related cytokines, such as IL-6, IL-1β, IL-17, and TNF-α, may contribute to disruption of the blood-brain barrier (BBB) and allow entry of the virus (104).…”