Communications Medicine (Apr 2025)

Distinct immune responses in people living with HIV following SARS-CoV-2 recovery

  • Dieter Mielke,
  • Shuying Sue Li,
  • Daniel J. Schuster,
  • Xiaohong Li,
  • Jiani Hu,
  • Shelly Karuna,
  • Kelly E. Seaton,
  • Caroline Brackett,
  • Brooke Dunn,
  • Taylor Keyes,
  • Adam Zalaquett,
  • Sherry Stanfield-Oakley,
  • Lu Zhang,
  • Martina S. Wesley,
  • Nathan Eisel,
  • Nicole L. Yates,
  • Xiaoying Shen,
  • Lakshmanane Premkumar,
  • Russell St. Germain,
  • Anton M. Sholukh,
  • Kristen Cohen,
  • Stephen de Rosa,
  • April Kaur Randhawa,
  • John A. Hural,
  • Lawrence Corey,
  • M. Julianna McElrath,
  • Georgia D. Tomaras,
  • Ollivier Hyrien,
  • Guido Ferrari

DOI
https://doi.org/10.1038/s43856-025-00839-1
Journal volume & issue
Vol. 5, no. 1
pp. 1 – 15

Abstract

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Abstract Background SARS-CoV-2 infection results in greater disease severity among immunocompromised individuals compared to healthy individuals. However, there is conflicting information about the impact of chronic HIV infection on immune responses to SARS-CoV-2 infection and vaccination. Method We used a combination of machine learning approaches and network analysis to explore 56 immune markers and comprehensively profile humoral and cellular immunity in a cross-sectional observational cohort of people without HIV (PWOH; n = 216) and people living with HIV (PLWH; n = 43) who recovered from SARS-CoV-2 infection (13–131 days since SARS-COV-2 diagnosis) early in the pandemic. Results PLWH recovered from symptomatic outpatient COVID-19 exhibit lower humoral and B cell responses to SARS-CoV-2 vs. PWOH but, surprisingly, both symptomatic outpatient and hospitalized PLWH have higher anti-endemic coronavirus antibody responses compared to PWOH counterparts and asymptomatic PLWH. The latter observation suggests that this was not strictly due to broadly elevated levels of anti-endemic coronavirus antibodies in PLWH. Moreover, correlation-based analysis reveals that while different compartments of the immune response to SARS-CoV-2 infection are positively correlated in PWOH recovered from symptomatic outpatient COVID-19, these correlations are weaker in PLWH. Conclusion Our analyses reveal significant differences in the coordinated immune responses elicited by infection in PLWH compared to PWOH.