HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave

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    Evaluation Summary:

    This manuscript is of primary interest to readers in the field of infectious diseases especially the ones involved in COVID-19 research. The identification of immunological signatures caused by SARS-CoV-2 in HIV-infected individuals is important not only to better predict disease outcomes but also to predict vaccine efficacy and to potentially identify sources of viral variants. In here, the authors leverage a combination of clinical parameters, limited virologic information and extensive flow cytometry data to reach descriptive conclusions.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

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Abstract

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes.

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  1. Author Response:

    Evaluation Summary:

    This manuscript is of primary interest to readers in the field of infectious diseases especially the ones involved in COVID-19 research. The identification of immunological signatures caused by SARS-CoV-2 in HIV-infected individuals is important not only to better predict disease outcomes but also to predict vaccine efficacy and to potentially identify sources of viral variants. In here, the authors leverage a combination of clinical parameters, limited virologic information and extensive flow cytometry data to reach descriptive conclusions.

    We have extensively reworked the paper.

    Reviewer #1 (Public Review):

    The methods appear sound. The introduction of vaccines for COVID-19 and the emergence of variants in South Africa and how they may impact PLWH is well discussed making the findings …

  2. Evaluation Summary:

    This manuscript is of primary interest to readers in the field of infectious diseases especially the ones involved in COVID-19 research. The identification of immunological signatures caused by SARS-CoV-2 in HIV-infected individuals is important not only to better predict disease outcomes but also to predict vaccine efficacy and to potentially identify sources of viral variants. In here, the authors leverage a combination of clinical parameters, limited virologic information and extensive flow cytometry data to reach descriptive conclusions.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

  3. Reviewer #1 (Public Review):

    The methods appear sound. The introduction of vaccines for COVID-19 and the emergence of variants in South Africa and how they may impact PLWH is well discussed making the findings presented a good reference backdrop for future assessment. Good literature review is also presented. Specific suggestions for improving the manuscript have been identified and conveyed to the authors.

  4. Reviewer #2 (Public Review):

    Karima, Gazy, Cele, Zungu, Krause et al. described the impact of HIV status on the immune cell dynamics in response to SARS-CoV-2 infection. To do so, during the peak of the KwaZulu-Natal pandemic, in July 2020, they enrolled a robust observational longitudinal cohort of 124 participants all positive for SARS-CoV-2. Of the participants, a group of 55 people (44%) were HIV-infected individuals. No difference is COVID-19 high risk comorbidities of clinical manifestations were observed in people living with HIV (PLWH) versus HIV-uninfected individuals exception made for joint ache which was more present in HIV-uninfected individuals. In this study, the authors leverage and combine extensive clinical information, virologic data and immune cells quantification by flow cytometry to show changes in T cells such as …

  5. Reviewer #3 (Public Review):

    Karim et al have assembled a large cohort of PLWH with acute COVID-19 and well-matched controls. The main finding is that, despite similar clinical and viral (e.g., shedding) outcomes, the immune response to COVID-19 in PLWH differs from the immune response to COVID-19 in HIV uninfected individuals. More specifically, they find that viral loads are comparable between the groups at the time of diagnosis, and that the time to viral clearance (by PCR) is also similar between the two groups. They find that PLWH have higher proportions and also higher absolute number of CD8 cells in the 2-3 weeks after initial infection.

    The authors do a wonderful job of clinically characterizing the research participants. I was most impressed by the attention to detail with respect to timing of viral diagnosis as it related to …

  6. SciScore for 10.1101/2020.11.23.20236828: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical statement and study participants: The study protocol was approved by the University of KwaZulu-Natal Institutional Review Board (approval BREC/00001275/2020).
    Consent: Adult patients (>18 years old) presenting either at King Edward VIII or Clairwood Hospitals in Durban, South Africa, between 8 June to 25 September 2020, diagnosed to be SARS-CoV-2 positive as part of their clinical workup and able to provide informed consent were eligible for the study.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Cells were then washed …