ABSTRACT The SARS-CoV-2 coronavirus 2019 (COVID-19) pandemic continues to impact the world and the fourth wave of the pandemic has Louisiana and the city of New Orleans leading in per capita cases and hospitalizations. There is an urgent and ongoing need to determine asymptomatic cases, treatment and health impacts of COVID-19. The pandemic has caused weeks of uncertainly, anxiety, and social isolation imposed by alarming infection rates and mandates for social distancing, self-quarantine, and shelter-in-place measures. Alcohol consumption can increase during times of duress and uncertainty and is often misused to cope with stress, anxiety, and depression. Minority populations and PLWH are vulnerable populations who have an excessively high rate of exposure to chronic and lifetime social stressors, linked to elevated rates of poorer mental health including depressive disorders, alcohol use disorders (AUDs), and post-traumatic stress disorder. Cognitive and behavioral deficits associated with AUD are commonly attributed to persistent neuro adaptations, as both former and current AUD patients demonstrate cognitive impairments including deficits in working memory, executive functioning, and impulsivity, all contributing to maladaptive decision-making. Excessive alcohol exposure also damages elements of the peripheral nervous system to produce a characteristic small fiber neuropathy, and the resulting hyperalgesia (or increased pain sensitivity) is hypothesized to contribute to motivational factors to drink. Our preliminary data identifies a state of hyperalgesia (increased pain sensitivity) in PLWH relative to HIV- negative individuals. Neurological deficits, such as cognitive decline and pain, have been associated with post- acute sequelae of COVID-19 (PASC). Our preliminary data also demonstrates a significant increase in alcohol use, smoking, and psychosocial stressors post government-issued restrictions to control COVID-19 in a cohort of PLWH and HIV-negative individuals. Our overarching hypothesis is that alcohol misuse increases the risk and severity of PACS. To test this hypothesis, our research team is prepared to conduct an ambidirectional study leveraging the New Orleans Alcohol Use and HIV (NOAH) longitudinal study cohort including both PLWH and HIV-negative individuals. Utilizing the existing NOAH cohort, we can respond in a timely manner with minimal start up time identifying asymptomatic cases and increasing access to care for on-going under reported health concerns in a vulnerable population. Data from our proposed NOAH-PACS study will characterize the full spectrum of PACS and emerging phenotypes of disease and identify risk factors for their development. Results will advance the science behind social determinants of comorbidities, alcohol use, and care-related outcomes among PLWH and those that are HIV-negative. Results of this proposal will inform the management of PACS and will inform future research projects to develop targets fo...