Postacute sequelae and adaptive immune responses in people with HIV recovering from SARS-COV-2 infection

  1. Michael J. Peluso
  2. Matthew A. Spinelli
  3. Tyler-Marie Deveau
  4. Carrie A. Forman
  5. Sadie E. Munter
  6. Sujata Mathur
  7. Alex F. Tang
  8. Scott Lu
  9. Sarah A. Goldberg
  10. Mireya I. Arreguin
  11. Rebecca Hoh
  12. Viva Tai
  13. Jessica Y. Chen
  14. Enrique O. Martinez
  15. Brandon C. Yee
  16. Ahmed Chenna
  17. John W. Winslow
  18. Christos J. Petropoulos
  19. Alessandro Sette
  20. Daniella Weiskopf
  21. Nitasha Kumar
  22. Kara L. Lynch
  23. Peter W. Hunt
  24. Matthew S. Durstenfeld
  25. Priscilla Y. Hsue
  26. J. Daniel Kelly
  27. Jeffrey N. Martin
  28. David V. Glidden
  29. Monica Gandhi
  30. Steven G. Deeks
  31. Rachel L. Rutishauser
  32. Timothy J. Henrich

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Abstract

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).

Methods:

We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 ( n  = 39 and n  = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2 infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.

Results:

Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8 + T cells ( P  = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4 + T cells ( P  = 0.007). Higher CD4 + /CD8 + ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8 + T cells (0.34-fold effect, P  = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P  = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.

Conclusion:

We identified potentially important differences in SARS-CoV-2-specific CD4 + and CD8 + T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

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  1. Version published to 10.1097/qad.0000000000003338
  2. Version published to 10.1101/2022.02.10.22270471v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.02.10.22270471: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Informed consent: The study was approved by the Institutional Review Board at the University of California, San Francisco (UCSF).
    Consent: All participants provided written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingSamples were assayed blinded with respect to associated patient and clinical information.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    For the primary analysis, we defined PASC as any COVID-19 attributed symptom that was present during a study visit >6 weeks following SARS-CoV-2 infection; this definition was selected because it is consistent with prior work and consensus definitions [48,49].
    PASC
    suggested: (PASC , RRID:SCR_016642)
    All samples were acquired on a BD LSR-II analyzer and analyzed with FlowJo X software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    This study has several limitations. The sample size was small, as relatively few PWH were infected with SARS-CoV-2 during the first year of the pandemic in our geographic area [73]. As there were few PWH without PASC, we were likely underpowered to make comparisons within the PWH sub-group; larger cohorts will be needed to do so. Our case definition, although potentially overly sensitive, is in line with consensus case definitions [16,17] and the association between HIV status and PASC was maintained in sensitivity analyses using more stringent definitions. However, given the nature of our recruitment, we emphasize that the high prevalence of PASC in our study cohort should not be considered to represent the population-level prevalence of this condition, which is likely much lower [27]. In addition, while the groups with and without HIV infection were well-matched on key variables demonstrated to be important in the immune response to SARS-CoV-2 infection and in PASC, the potential for residual confounding remains. For example, data on additional clinical factors that may be related to both HIV status and PASC, including comorbid mental health conditions and substance use, were unavailable. We used concurrent CD4+ T cell count and CD4/CD8 ratio as markers of immune reconstitution; CD4+ T cell nadir might be an important factor but we were unable to confirm these values in most participants due to fragmentation of healthcare records. Regarding laboratory measurements, we used ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04362150RecruitingLong-term Impact of Infection With Novel Coronavirus (COVID-…

    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.

    About SciScore

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  4. Version published to 10.1101/2022.02.10.22270471v1 on medRxiv