Associations between HIV infection and clinical spectrum of COVID-19: a population level analysis based on US National COVID Cohort Collaborative (N3C) data

Abstract

Background: Evidence of whether people living with HIV are at elevated risk of adverse COVID-19 outcomes is inconclusive. We aimed to investigate this association using the population-based National COVID Cohort Collaborative (N3C) data in the USA.

Methods: We included all adult (aged ≥18 years) COVID-19 cases with any health-care encounter from 54 clinical sites in the USA, with data being deposited into the N3C. The outcomes were COVID-19 disease severity, hospitalisation, and mortality. Encounters in the same health-care system beginning on or after January 1, 2018, were also included to provide information about pre-existing health conditions (eg, comorbidities). Logistic regression models were employed to estimate the association of HIV infection and HIV markers (CD4 cell count, viral load) with hospitalisation, mortality, and clinical severity of COVID-19 (multinomial). The models were initially adjusted for demographic characteristics, then subsequently adjusted for smoking, obesity, and a broad range of comorbidities. Interaction terms were added to assess moderation effects by demographic characteristics.

Findings: In the harmonised N3C data release set from Jan 1, 2020, to May 8, 2021, there were 1 436 622 adult COVID-19 cases, of these, 13 170 individuals had HIV infection. A total of 26 130 COVID-19 related deaths occurred, with 445 among people with HIV. After adjusting for all the covariates, people with HIV had higher odds of COVID-19 death (adjusted odds ratio 1·29, 95% CI 1·16-1·44) and hospitalisation (1·20, 1·15-1·26), but lower odds of mild or moderate COVID-19 (0·61, 0·59-0·64) than people without HIV. Interaction terms revealed that the elevated odds were higher among older age groups, male, Black, African American, Hispanic, or Latinx adults. A lower CD4 cell count (<200 cells per μL) was associated with all the adverse COVID-19 outcomes, while viral suppression was only associated with reduced hospitalisation.

Interpretation: Given the COVID-19 pandemic's exacerbating effects on health inequities, public health and clinical communities must strengthen services and support to prevent aggravated COVID-19 outcomes among people with HIV, particularly for those with pronounced immunodeficiency.

Funding: National Center for Advancing Translational Sciences, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

Figure 1

Study participant selection *The numbers for missing race data and missing ethnicity data did not add up to 730 because some records missed both data.

Figure 2

Estimates for the associations between HIV status and COVID-19 clinical spectrum outcomes (A) Mild or moderate disease. (B) Severe disease. (C) Hospitalisation. (D) Death. All stratified models (by age, sex, and race) were adjusted for age, sex, race, ethnicity, smoking, BMI, and comorbidities, including hemiplegia or paraplegia, dementia, liver disease, myocardial infarction, congestive heart failure, chronic pulmonary disease, cancer, diabetes, stroke, peripheral vascular disease, rheumatologic disease, renal disease, and peptic ulcer disease. Mild COVID-19 includes both the mild (outpatient, WHO severity 1–3) and mild emergency department (outpatient with emergency department visit, WHO severity ∼3) categories. Moderate COVID-19 includes patients who were hospitalised but without invasive ventilation (WHO severity 4–6). Severe COVID-19 includes both severe (hospitalised with invasive ventilation or extracorporeal membrane oxygenation, WHO severity 7–9) and mortality or hospice (hospital mortality or discharge to hospice, WHO severity 10) categories based on WHO criterion. BMI=body-mass index.