Auditory Insights into Post-Acute Sequelae of SARS-CoV-2 Infection: Unveiling Abnormal Auditory Perception and Diagnostic Markers through Complex Auditory Performance Tests. - Summary: Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) include auditory symptoms such as impaired speech understanding in background noise, increased ringing in the ears (tinnitus), and heightened sound sensitivity (hyperacusis). These symptoms likely originate in the central nervous system (CNS), not the ear, and so reflect CNS involvement in PACS. This means that tests of the brain’s ability to process sound (Complex Auditory Performance Tests - CAPTs) might provide a window into CNS dysfunction in PASC and may be related to other prevalent subjective PASC symptoms such as cognitive fatigue. If so, CAPTs would offer an innovative and objective way to diagnose and track patients with PASC. We compared performance on a central-auditory- focused test battery between 40 individuals with PASC to 36 controls. This work showed PASC patients had: 1) increased prevalence of self-reported abnormal perceptions/reactions to sound such as ringing in the ears and inability to tolerate loud sounds, 2.) worse performance on a challenging behavioral CAPTs, and 3.) increased auditory brainstem response V/I amplitudes that resemble the neurophysiological profile of aberrant sound perception and suggests dysregulated central gain. The objective of this project seeks to expand on this work and evaluate CAPTs as tools to assess CNS function in PASC. Building on the team's preliminary work and leveraging expertise in auditory processing, neuropsychology, and statistics, the research goal is to link CNS function and subjective cognitive concerns in persons with PASC, providing an approach to identifying the relationship between the CNS, neurocognitive symptomology (cognitive fatigue), and auditory processing in individuals with PASC. Three specific aims will focus on: 1.) quantifying subjective auditory symptomology, 2.) determining auditory deficits using an improved suite of behavioral CAPTs, and 3.) assessing alterations in neural gain in individuals with PASC using an expanded set of neurophysiological tests focused central auditory processing. The expected outcome is a comprehensive understanding of auditory symptomology and the identification of deficits in behavioral and neurophysiological CAPTs, offering potential diagnostic markers for PASC and paving the way for their use in tracking treatment effects. The project capitalizes on a unique clinic at Dartmouth-Hitchcock Medical Center dedicated to the diagnosis and treatment of PASC and unites a multidisciplinary team. The PI and study team have extensive experience in using CAPTs to assess the neurocognitive effects of viral infections from their work with individuals living with HIV. The results are anticipated to provide evidence-based proof of principal for CAPTs' development as crucial diagnostic tools for PASC and potentially other conditions with diffuse CNS dysfunction.