Project Summary/Abstract During the Coronavirus (COVID)-19 pandemic, the number of patients diagnosed with the acute respiratory distress syndrome (ARDS) has increased dramatically in the US. COVID-19-associated ARDS is characterized by high morbidity, including a requirement for protracted mechanical ventilator support. In a substantial percentage of patients who survive hospitalization, deficits including neurocognitive dysfunction and residual pulmonary impairment have been reported as so-called Post-Acute Sequelae of COVID-19 (PASC). Therefore, it is imperative to urgently establish addressable factors that drive poor outcomes. Prior to the COVID-19 pandemic, investigations by our research group demonstrated that alcohol misuse is associated with an increased severity of ARDS, which may contribute to residual pulmonary dysfunction in survivors. Alcohol misuse can also propagate development of delirium that may increase risk for cognitive impairment in recovery. Notably, delirium has been reported in half of all COVID-19 patients in the ICU, and alcohol misuse appears to increase odds for its development. Although reports of increasing alcohol misuse during the pandemic are widespread and might be one modifiable factor driving severity of illness and outcomes, its impact on the trajectory of illness in COVID-19 has not been fully evaluated. The goal of this proposal is to determine if alcohol misuse promotes ICU delirium that in turn increases requirements for mechanical ventilation among patients with COVID-19-associated ARDS. Also, we wish to establish if alcohol misuse contributes to persistent cognitive and respiratory PASC in COVID-19 survivors. To address these questions, two aims are proposed. Aim 1: In hospitalized patients with COVID-19-associated ARDS, determine if alcohol misuse is associated with increased mechanical ventilation requirements, and if delirium further influences this relationship. Investigations will be conducted in a prospectively enrolled cohort of patients with COVID-19- associated ARDS, who are in the ICU at the University of Colorado Hospital (Aim 1a), and in a retrospective cohort of hospitalized patients with COVID-19, previously admitted in the University of Colorado Health system (Aim 1b). Aim 2: Among patients recovering from COVID-19, determine the impact of alcohol misuse on cognition and respiratory function in recovery, accounting for characteristics of acute illness that include requirements for mechanical ventilation and ICU delirium. Investigations will be conducted in patients followed in a multidisciplinary COVID-19 Recovery Clinic, who will have cognitive, mental, and respiratory health evaluated over the year following hospital discharge. Our proposed research will help determine if patients with alcohol misuse warrant targeted strategies to identify and treat delirium in the setting of COVID-19-associated respiratory failure, and it will clarify if hospitalized patients with COVID-19 and alcohol misuse represent a unique subgroup at risk for PASC who may merit specific services or interventions.

Project Narrative Alcohol misuse exists among many patients in the intensive care unit, and is often associated with respiratory failure. Infection with Coronavirus (COVID)-19 commonly causes respiratory failure, along with a type of abnormal brain function known as delirium, both of which may have lasting effects on health. This proposal will determine the role of alcohol misuse and delirium on short- and long-term brain and lung function in patients who have been hospitalized with COVID-19-associated respiratory failure.