ABSTRACT COVID-19 cases continue to rise, with over 3,000,000 cases and 130,000 deaths in the US and almost 12 million cases worldwide 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 other organ and blood systems. Studies document more severe disease and higher mortality among people who are older and/or have co-morbidities, such as hypertension, diabetes, obesity, and chronic lung disease. However, there is a paucity of data regarding the acquisition, occurrence and severity of infection among people with HIV (PWH). There is also little data to guide prevention and treatment recommendations for this population, many of whom are older and have comorbidities that may increase not only their risk for acquiring infection, but also the morbidity and mortality among those who acquire infection. Moreover, early reports suggest substantial racial disparities in US COVID-19 rates, with increases in mortality among African Americans. The MACS- WIHS Combined Cohort Study (MWCCS), the largest and longest-running observational cohort of men and women living with or at risk for HIV in the US provides a unique opportunity to address important knowledge gaps in the acquisition, occurrence, severity and outcomes of COVID-19. The MWCCS is a geographically and racially/ethnically diverse cohort of aging men and women with a high prevalence 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 measures including pulmonary, cardiac, kidney, neurocognitive, and physical function, body composition and has performed cohort-wide genome association studies. The overarching goal of this application is to understand the impact of the COVID-19 epidemic among US men and women with or at risk for HIV infection and to evaluate host factors that contribute to disease acquisition, expression, severity and recovery. The proposed studies will determine COVID incidence, short- term and long-term clinical outcomes, including thrombotic and pulmonary sequelae, and how racial and geographic disparities; immune and genetic risk factors impact these outcomes in the MWCCS.

Narrative This research would contribute to improved understanding of COVID-19 manifestations, the social factors that drive distribution and outcomes of disease in vulnerable populations, pathophysiologic and genetic factors, as well as the interactions between comorbid conditions, such as HIV. Improved understanding of these factors could improve care and aid development of therapies, and inform efforts to control future outbreaks.