BRAIN-2 Administrative Supplement with ORCHID-BUD

Medical teams globally are consumed in caring for patients with respiratory failure and acute comorbiditiescaused by Coronavirus Disease 2019 (COVID-19). To understand the full impact of this pandemic on the livesof survivors and the magnitude of this emerging public health crisis, we must study the brain. We helped definethe plague of disabling features suffered by millions of intensive care unit (ICU) survivors called Post-IntensiveCare Syndrome (PICS), characterized by an acquired Alzheimer's disease and related dementia (ADRD), post-traumatic stress disorder (PTSD), and depression. Approximately 10% to 15% of COVID-19 patients develophypoxemia requiring hospitalization, which can lead to acute respiratory distress syndrome and the need forlife support, including mechanical ventilation. Up to 26% of hospitalized patients with COVID-19 require ICUadmission. We hypothesize that COVID-19 survivors who are hospitalized will have a high burden of PICS-related acquired-ADRD, PTSD, and depression. To test this hypothesis, we propose this NIH AdministrativeSupplement to the BRAIN-ICU-2 Study (R01AG058639). This Administrative Supplement will allow us to usethe BRAIN-ICU-2 long-term follow-up infrastructure to collect 6-month cognition, PTSD, and depression datafor a NHLBI-sponsored randomized trial (ORCHID) that is evaluating hydroxychloroquine versus placebo on15-day death, mechanical ventilation, or oxygen supplementation. We will ascertain these 6-month outcomesusing a comprehensive phone battery that incorporates robust neuropsychological tests for memory, attention,language, reasoning, and executive function, and diagnostic evaluations for PTSD and depression. OurAdministrative Supplement is titled "Outcomes Related to COVID-19 treated with Hydroxychloroquine amongIn-patients with symptomatic Disease - Brain Outcomes and Psychological Distress (ORCHID-BUD)" and willconduct 6-month follow-up assessments in 270 adults who are hospitalized with COVID-19 infection andsurvive. ORCHID-BUD has the following specific aims: (1) To determine the epidemiology (i.e., prevalence) ofcognitive impairment (i.e., acquired-dementia) at 6 months and if hydroxychloroquine administration isassociated with improvement in these same outcomes; (2) To determine the epidemiology of PTSD anddepression at 6-months, and if hydroxychloroquine administration is associated with improvement in thesesame outcomes, and (3) To identify modifiable risk factors (e.g., sedatives, isolation, intravenous fluids,pressor, ACE-inhibitor or ARB use, etc.) associated with worse long-term cognitive impairment, PTSD, anddepression at 6 months. To our knowledge, this investigation will be the first ever to conduct robustneuropsychological assessments for SARS, MERS or COVID-19 survivors, and the first among COVID-19 toconduct diagnostic PTSD and depression assessments. This Administrative Supplement will leverage BRAIN-ICU-2 and ORCHID's resources to conduct a high impact and novel investigation at relatively low cost and helpprovide a comprehensive evaluation of COVID-19's effect on long-term cognitive and psychological outcomes.