The Role of HIV Infection in the Clinical Spectrum of COVID-19: A Population-Based Cohort Analysis Based on US National COVID Cohort Collaborative (N3C) Enclave Data

Background: Evidence of whether people living with HIV (PLWH) are at elevated risk of adverse COVID-19 outcomes is limited. We aimed to investigate this association using the population based National COVID Cohort Collaborative (N3C) data in the US. Methods: The harmonized, high-granularity electronic health record data from 54 clinical sites in N3C were used for this study. Logistic and multinominal logistic regression models were employed to estimate the association between HIV infection and hospitalization, mortality and clinical severity of COVID-19, with models being initially adjusted for age and sex, then cumulatively adjusted for race and ethnicity, smoking and obesity, and a broad range of comorbidities. Interaction terms were added to assess modification effect by age, sex, and race. Findings: Among a total of 1,436,622 adult COVID-19 cases between January 2020 and May 2021, 13,170 had HIV infection. A total of 26,130 deaths occurred, with 445 among PLWH. PLWH had higher risk of COVID-19 death and hospitalization than non-PLWH after adjusting for age and sex. The associations were attenuated, but remained significant, after adjusting for lifestyle factors and comorbidities (COVID-19 death: [adjusted OR(AOR): 1.38; 95%CI: 1.25-1.54]; hospitalization: [AOR: 1.23; 95%CI: 1.18-1.28]). In terms of COVID-19 disease severity, PLWH were less likely to have mild/moderate illness but more likely to have severe illness when only controlling for demographics, smoking and BMI, although the estimated risk was obviated after controlling for comorbidities. Interaction terms revealed that the elevated risk was higher among older age group, males and black/African American. Interpretation: PLWH in the US had increased risk of COVID-19 hospitalization and mortality comparing with non-PLWH. The adverse COVID-19 outcomes might not only be accounted for by HIV but also by other risk factors that are highly prevalent in PLWH. Funding Information: National Center for Advancing Translational Sciences, National Institute of Allergy And Infectious Diseases, US. Funding Information: NCATS U24 TR002306 and the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R01AI127203-4S1. Declaration of Interests: None to declare. Ethics Approval Statement: The study protocol received approval from the institutional review board in University of South Carolina. National Institute of Health’s (NIH) National COVID Cohort Collaborative (N3C) Data Utilization Request Approval committee approved the data utilization request of this project (RPE72986).