Deciphering mechanisms of COVID-19 induced anosmia

Project Summary/Abstract In this Competitive Revision proposal, we seek to investigate the non-cell autonomous effects of Covid-19 infections in olfaction. Our preliminary data suggest that induction of pro-inflammatory/antiviral pathwaysresult in disruption of inter-chromosomal genomic interactions, and downregulation of Olfactory Receptor (OR)gene expression. Since antiviral responses are expected be elicited upon Covid-19 infection, we hypothesizethat disruptions in nuclear architecture and OR expression account for the reported olfactory deficits in infectedpatients. Thus, we propose to analyze human autopsies of the olfactory epithelium, to decipher whether Covid-19 infections disrupt genomic interactions required for OR transcription. We will complement our studies inhuman autopsies with experiments using mice infected with SARS-CoV-2. RNA-seq, in situ HiC andimmunohistochemistry experiments in human and mice will reveal the molecular mechanisms by which Covid-19 induces olfactory dysfunction. Our experiments will provide critical insight to the mechanisms by which thevirus hijacks molecular and physiological processes of the host cell, opening new potential avenues for theprevention, diagnosis and treatment of Covid-19 infection.