Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study examines the SARS-CoV-2 immunity in an HIV positive population including the possible effects of comorbidities. It appears scientifically sound and in line with many other published observations.

Lines 62-63: The way this is written, it sounds like addiction and/or mental health challenges are common comorbidities with HIV/HCV co-infection. Provide citation(s) for this assertion.

Section 2.1 Laboratory Studies: The description of the in-house ELISA assay should be recapitulated in enough detail to ensure repeatability. While the citations are helpful, key parameters such as the plates uses (which is critical in the interpretation of well volumes provided), how plates were coated including antigen concentration, and what antibodies were used for detection including their concentration.

Section 2.2 Statistical Methods: At a minimum, please provide R package and versions used for statistical modeling. It may be prudent to include R scripts in a repository or as an appendix. Additionally, many statistical tests are named in this section, but it is unclear when each was used in the data analysis. Please update this section so that the reader can understand which tests were used for which reported data analysis.

Table 1 seems to point out that there are many significant differences between the CTN222 and CTN314 cohorts. This is particularly poignant for HCV co-infection. However, these differences are not addressed in the text.

Throughout the manuscript mental health is mentioned, however the only metric captures is self-reported depression. The authors should update the terminology from “mental health” to “major depressive disorder (MDD)”. Additionally, it is unclear whether self-reported current depression means a current diagnosis for MDD, treatment for MDD, or if the questionnaire was less specific.

Minor/grammatical comments

Define abbreviations at first use (e.g. HIV line 45; SARS CoV-2 line 47; REB line 81; RED line 101; BAU line 116

Line 74-75: seems to be missing a word: various social, [and] demographic [factors,] and therapies…

Line 96: “included” should be “including”

Line 108 & 109 ul/well should be μl/well

Line 268: There are protective levels of antibodies, but a universal threshold has not been established. Please revise this statement for clarity (with citations if necessary).

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript addresses an important topic, namely the immune response to COVID-19 vaccination and SARS-CoV-2 infection in populations of persons living with HIV who may be at increased risk of adverse outcomes. The study population and longitudinal follow-up are valuable. However, several issues related to clarity and structure should be addressed before the manuscript can be considered for publication.

Major Comments

1. It would be helpful to clarify the description of the two study cohorts in the first sentence of the abstract. The current wording makes it difficult to clearly identify the two groups under investigation. Please clarify that the cohorts consist of (1) persons living with HIV with hepatitis C virus (HCV) coinfection and (2) persons living with HIV aged ≥65 years.

2. Please clarify the abbreviation HCV at its first appearance in the abstract by defining it as hepatitis C virus (HCV).

3. It would be helpful to clarify that all 471 participants included in the analysis were persons living with HIV. This should be explicitly stated in the Methods section.

4. The authors should clarify the number of participants in each cohort (HIV–HCV coinfection and individuals aged ≥65 years). Providing these numbers in the Methods section would improve transparency.

5. Potential control cohort - Please clarify whether a third cohort (e.g., HIV-negative healthy controls) was included in the broader study. If such a cohort exists but was not included in the present analysis, the authors should briefly explain the rationale for its exclusion.

6.   The introduction would benefit from additional background explaining the immunological relevance of the SARS-CoV-2 antigens measured in the study, namely the spike trimer, receptor binding domain (RBD), and nucleocapsid (N) protein. In particular, it would be helpful to briefly describe the role of these viral proteins and the significance of antibody responses against them during natural infection and following vaccination. This would help readers better interpret the presented serological results.

7. Figure 1. Please clarify and briefly explain the use of violin plots in the figure legend or Methods section. Since not all readers may be familiar with this type of data visualization, a short explanation of what the violin plots represent    

8.   The Discussion places the findings in the context of previous studies and appropriately highlights the high rates of seroconversion and vaccine uptake in this population. However,  the authors may wish to briefly acknowledge the limitations of using binding antibody levels as a surrogate marker of protection, including the role of neutralizing antibodies and cellular immunity.   

9.   The manuscript does not appear to discuss the types of COVID-19 vaccines received by participants. Since different vaccine platforms (e.g., mRNA vs viral vector vaccines) can induce different magnitudes and durability of antibody responses, it would be helpful to clarify which vaccine types were administered in the cohort. If multiple vaccine types were used, the authors should consider discussing whether this may have influenced the observed antibody responses or acknowledge this as a potential limitation.  

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

My prior concerns have been addressed and I am comfortable recommending  publication of this manuscript in its current form.