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

  1. Jing Sun
  2. Rena C. Patel
  3. Qulu Zheng
  4. Vithal Madhira
  5. Amy L. Olex
  6. Jessica Y. Islam
  7. Evan French
  8. Teresa Po-Yu Chiang
  9. Hana Akselrod
  10. Richard Moffitt
  11. G. Caleb Alexander
  12. Kathleen M. Andersen
  13. Amanda J. Vinson
  14. Todd T. Brown
  15. Christopher G. Chute
  16. Keith A. Crandall
  17. Nora Franceschini
  18. Roslyn B. Mannon
  19. Gregory D. Kirk
  20. National COVID Cohort Collaborative (N3C) Consortium

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Abstract

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.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.26.21261028: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: 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.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    HIV infection was defined by (1) HIV condition (ICD codes), (2) HIV-related laboratory results (ELISA antibody test or detection of HIV viral load), (3) HIV-related medications (antiretroviral therapy, [ART]) excluding pre-exposure prophylaxis (Supplementary Table S-1).
    antiretroviral therapy ,
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    History of HIV infection, SOT, comorbid conditions, demographics (age, sex, race and ethnicity [non-Hispanic Black, non-Hispanic White, Hispanic, others]), smoking history (never vs. ever vs. unknown), and study sites were extracted using custom concept sets developed from International Classification of Diseases (ICD) codes, Current Procedural Terminology (CPT) codes, and other medical codes (Supplementary table S-1 lists concept sets and codes used in definitions).
    non-Hispanic White
    suggested: None

    Results from OddPub: Thank you for sharing your code.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Despite the largest and the most representative sample to date for a U.S. population 17,18, our study has limitations. First, N3C primarily compiled data from large academic medical centers funded by NCATS. Therefore, it may be less representative of admission practices and disease severity in other settings. There has historically been a low threshold to admit PWH and SOT to these hospital because of their underlying disease. While this might have contributed somewhat to increased likelihood of hospitalization with mild/moderate disease, it would not account for the independent increased odds for ventilation among persons that were hospitalized in these groups. Potential misclassification of key exposures (e.g. HIV status, SOT, or other comorbidities) may occur due to inherent limitations of EMR data. In particular, we were more likely to identify PWH who were successfully engaged in care due to reliance on ICD codes, ART, and laboratory results in the past 2 years to define HIV status. However, HIV or SOT are unlikely to be missed on admission diagnoses due to their clinical importance. Further, these potential misclassifications are likely to be non-differential throughout the cohort and unlikely to change our conclusions. HIV laboratory values (CD4 cell counts and HIV viral load) were not universally available across all study sites and individuals. Differential laboratory assays and protocols across sites added further complexity for data harmonization and validation. Ho...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.07.26.21261028 on medRxiv