NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial

Round 1

Reviewer 1 Report

Dear Editor,

Moll-Bernades and colleagues conducted a translational research project exploring the key immune cell profile in patients with history of hypertension, who required hospitalization for COVID-19. 156 patients were included in this study. Among other findings, the researches reported that NKG2A expression among CD8 cells was associated with progression to severe COVID-19.

I would like to thank you for the opportunity to review this work. I would also like to commend the authors. Please see my comments below:

General comment:

·         The main limitation of the study is the small population (N=156), although some one can argue that 156 patients is not a low number for a translational research project. The authors attempted to be as robust as possible in their statistical approach to mitigate this limitation.

Introduction:

• *The first sentence “Risk factors … COVID-19” needs some references. Among the plethora of available research, I would recommend PMID: 35160073, PMID: 33123973, PMID: 32422233, PMID: 33956286 
• The background is nicely written and the objective is clearly defined.

Methods:

• 2.1: I would remove the word “diagnoses” after COVID-19 in line 4 of 2.1 
• I would change “hypertensive patients” to “patients with hypertension”
• I would change “chronic … users” to “were on treatment with ACEI/ARB at baseline”
• I would change “coronary disease” to “coronary artery disease”
• Methods appear to be appropriate overall.  

Results:

• I would remove the phrase “in the present study … patients”
• I would change “were obese” to “had obesity”
• Consider presenting data on in-hospital death (n, %)

Discussion:

• I would rephrase the 1^st sentence of discussion.
• I would actually rephrase the whole 1^st paragraph of discussion.
• Otherwise, discussion is appropriate.

Author Response

Responses to Reviewer

1. General comment:

• The main limitation of the study is the small population (N=156), although some one can argue that 156 patients is not a low number for a translational research project. The authors attempted to be as robust as possible in their statistical approach to mitigate this limitation.

Response: We appreciate these comments from the reviewer.

2. Introduction:

*The first sentence “Risk factors … COVID-19” needs some references. Among the plethora of available research, I would recommend PMID: 35160073, PMID: 33123973, PMID: 32422233, PMID: 33956286 

Response: We thank the reviewer for these suggestions, and we have included the recommended references to better support our introduction.

The background is nicely written and the objective is clearly defined.

Response: We thank the reviewer for the acknowledgement.

Methods:

• 1: I would remove the word “diagnoses” after COVID-19 in line 4 of 2.1

Response: the word diagnoses was removed.

• I would change “hypertensive patients” to “patients with hypertension”

Response: We changed as recommended.

• I would change “chronic … users” to “were on treatment with ACEI/ARB at baseline”

• Response: We changed as recommended

• I would change “coronary disease” to “coronary artery disease”

Response: we corrected accordingly in methods section and also in Table1.

• Methods appear to be appropriate overall. 

Response: Thank you for this comment

Response: We are very grateful for all this suggestion to improve the clarity of the paper and we did the modifications accordingly.

Results:

• I would remove the phrase “in the present study … patients”

Response: the phrase was removed as suggested.

• I would change “were obese” to “had obesity”

Response: We changed as suggested.

• Consider presenting data on in-hospital death (n, %)

Response: We thank the reviewer for these recommendations that improved our text. We included data regarding in-hospital death in the text (item 3.1 Outcomes)

Discussion:

• I would rephrase the 1^st sentence of discussion.
• I would actually rephrase the whole 1^st paragraph of discussion.
• Otherwise, discussion is appropriate.

Response: The first paragraph was entirely rephased, according to the reviewer’s recommendation and we are thankful for this suggestion.

Reviewer 2 Report

The paper is very interesting. The study was well conducted, and the manuscript was well-written and argued. 

I believe this paper could be of interest to the readers as it highlights novel data that further explain molecular pathways triggered by SARS-CoV-2 infection and lead to severe forms of COVID-19 disease. 

The introduction provides an adequate background and the discussion is complete and well-argued. Method and Results are clearly presented. The authors pointed out the limitations of the study which was correct. 

Author Response