COVID-19 and the MWCCS: Pathophysiology, Impact and Outcomes

COVID-19 and the MWCCS: Pathophysiology, Impact and OutcomesAbstract: COVID-19 cases continue to rise, with over 3,000,000 cases and 130,000 deaths in the US[1] and almost 12million cases worldwide[2] to date. Manifestations of SARS CoV-2 infection range from asymptomatic to mild,moderate, or severe disease, and primarily affects the lung, but increasing data suggests involvement of otherorgan and blood systems.[3] Studies document more severe disease and higher mortality among people whoare older and/or have co-morbidities, such as hypertension, diabetes, obesity, and chronic lung disease.[4-7]However, there is a paucity of data regarding the acquisition, occurrence and severity of infection amongpeople with HIV (PWH). There is also little data to guide prevention and treatment recommendations for thispopulation, many of whom are older and have comorbidities that may increase not only their risk for acquiringinfection, but also the morbidity and mortality among those who acquire infection. Moreover, early reportssuggest substantial racial disparities in US COVID-19 rates, with increases in mortality among AfricanAmericans.[8] The MACS-WIHS Combined Cohort Study (MWCCS), the largest and longest-runningobservational cohort of men and women living with or at risk for HIV in the US provides a unique opportunity toaddress important knowledge gaps in the acquisition, occurrence, severity and outcomes of COVID-19. TheMWCCS is a geographically and racially/ethnically diverse cohort of aging men and women with a highprevalence of risk factors for progression to severe COVID-19 disease including hypertension, diabetes,obesity, and smoking. The MWCCS has a rich biorepository of specimens, collects rigorous clinical measuresincluding pulmonary, cardiac, kidney, neurocognitive, and physical function, body composition and hasperformed cohort-wide genome association studies. The overarching goal of this application is to understandthe impact of the COVID-19 epidemic among US men and women with or at risk for HIV infection and toevaluate host factors that contribute to disease acquisition, expression, severity and recovery. The proposedstudies will determine COVID incidence, short-term and long-term clinical outcomes, including thrombotic andpulmonary sequelae, and how racial and geographic disparities; immune and genetic risk factors impact theseoutcomes in the MWCCS.