COVID-19 Disease Severity Among People With HIV Infection or Solid Organ Transplant in the United States: A Nationally-Representative, Multicenter, Observational Cohort Study

Background: Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction. Methods: We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction. Findings: Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm 3 , PWH with CD4<350 cells/mm 3 were independently at 4.4-, 5.4-, and 7.6-times higher odds for hospitalization, requiring ventilation, and death, respectively. Increased COVID-19 severity was associated with higher levels of HIV viremia. Interpretation: Individuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT. Funding Information: NCATS U24 TR002306. ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Dr. Gregory Kirk is supported in part by NIAID K24AI118591. Dr. Rena C. Patel’s effort was supported by NIAID of the NIH (K23AI120855). Ms. Andersen received doctoral training support from the National Heart, Lung and Blood Institute Pharmacoepidemiology T32 Training Program (T32HL139426). Dr. Todd Brown is supported in part by NIAID K24AI120834. Declaration of Interests: None to declare. Ethics Approval Statement: The N3C Data Enclave is approved under the authority of the NIH Institutional Review Board (IRB, IRB00249128) with Johns Hopkins University School of Medicine as a central IRB for data transfer. Institutional IRB at each study site approved the study protocol or ceded to this single IRB. The current study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.