The Efficacy of COVID-19 Vaccines in Chronic Kidney Disease and Kidney Transplantation Patients: A Narrative Review
Round 1
Reviewer 1 Report
In the review by Hou et al, the authors provide a comprehensive examination of the COVID-19 high risks in patients suffering from chronic kidney disease (CKD) or those receiving a kidney transplant. The authors highlight COVID-19 vaccine efficacy in patients receiving various treatments to lower their immune systems. This review provides important evidence on the effects of immunosuppressants and vaccination responses for individuals suffering from CKD. Most importantly, this work provides awareness to the importance of creating specific vaccination protocols for these patients. The manuscript is well written but deserves another round of revision for grammar and style. There are a series of typos and unclear acronyms that need correction. Please see my comments below:
Line 17: Please add the abbreviated form for chronic kidney disease in this line.
Line 22: the sentence should read: “chronic use of immunosuppressive agents…”
The abstract will benefit of a final sentence that highlights the important of this review (i.e. vaccination protocols for CKD patients)
Line 60: please add the abbreviated form for renin-angiotensin-aldosterone system (RAAS) in this sentence.
Line 77: “ESRD” should be define in line 75-76
Line 112: “a dose of 1011 viral particles” is this referring to 10e11 or ~10e3 viral particles? Please correct.
Line 117: “perfusion transformation by proline”. I think the authors are describing a prefusion state of the spike protein when prolines are added at specific places. This sentence should be rewritten.
Line 136: “infection28” typo
Line 152: CKD stages should be referred as CKD3 and CKD5
Line 155: include the abbreviated form for kidney transplantation in the tittle of Table 1
Table 1: for clarity the authors should use the same subtitles that describe the different COVID-19 vaccines available (i.e., subunit, viral vectors, etc.) Change “purified virus components for subunit vaccines. Vertical lines for each of the columns should add more clarity to the table.
Line 326: “T cells61” typo
Line 328: “hematglutin” typo
Line 341: it should read “study by Garcia Jr. et al.,
Author Response
First, we would like to thank the Reviewers’ for critically reviewing this manuscript and providing us many invaluable comments and suggestions. We responded to each of the reviewers’ comments and clarified/amended every necessary part raised by the reviewer. The detailed statements, reviewer-by-reviewer, and point-by-point are enclosed as following. We highly appreciate all your help and further arrangement. We hope that the revised version of the manuscript could meet the academic standard of Vaccines.
Yours truly,
Ko-Lin Kuo, MD. PhD
Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City
E-mail: [email protected]
Reviewer 1 comment:
- Line 17: Please add the abbreviated form for chronic kidney disease in this line.
Ans:
Thank you for your suggestion. We have added the abbreviation at this line. - Line 22: the sentence should read: “chronic use of immunosuppressive agents…”
Ans:
Thank you for your valuable comment. We have revised the sentence according to the reviewer’s comment accordingly. - The abstract will benefit of a final sentence that highlights the important of this review (i.e. vaccination protocols for CKD patients)
Ans:
Thank you for the valuable comments. We would add the relevant sentence in the abstract in line 25 as follows:
Boosting dosage more than the protocol might increase the titer of the neutralizing antibody in CKD patients. - Line 60: please add the abbreviated form for renin-angiotensin-aldosterone system (RAAS) in this sentence.
Ans:
Thank you for the reminding on the abbreviation RAAS. We added the abbreviation accordingly. - Line 77: “ESRD” should be define in line 75-76
Ans:
Thank you for reminding. We added the definition at line 75-76 with end-stage renal disease accordingly. - Line 112: “a dose of 1011 viral particles” is this referring to 10e11 or ~10e3 viral particles? Please correct.
Ans:
Thank you for reminding. It is a dose of 10e11. We revised the sentence accordingly. - Line 117: “perfusion transformation by proline”. I think the authors are describing a prefusion state of the spike protein when prolines are added at specific places. This sentence should be rewritten.
Ans:
Thank you for the valuable comment. We re-write the sentence to provide the more proper expression as follows:
For BNT162b2, the full-length RNA with 2 mutation modified by proline can translate the locked-in perfusion transformation in order to augment the production of neutralizing antibody - Line 136: “infection28” typo
Ans: Thank you for the reminding. We correct the typo according. - Line 152: CKD stages should be referred as CKD3 and CKD5
Ans: Thank you for reminding. We rephrased into CKD stage 3-5. - Line 155: include the abbreviated form for kidney transplantation in the tittle of Table 1
Ans: Thank you for the comment on the abbreviation for kidney transplantation. We added the abbreviation with kidney transplantation as KT in line 18 in abstract and line 45 in the manuscript and table 1 legend in line 156. - Table 1: for clarity the authors should use the same subtitles that describe the different COVID-19 vaccines available (i.e., subunit, viral vectors, etc.) Change “purified virus components for subunit vaccines. Vertical lines for each of the columns should add more clarity to the table.
Ans:
Thank you for the comments on the consistency of the table and the subtitle of the manuscript. We modify the subtitle in line 111, line 134 in order to make the consistency with the table. We also modify the vertical lines to clarify the subtitle of the table and different categories. - Line 326: “T cells61” typo:
Ans:
Thank you for reminding. We rephased the sentence into T cells [61] with reference. - Line 328: “hematglutin” typo
Ans: Thank you for reminding. After reviewing the sentence, we deleted the typo. - Line 341: it should read “study by Garcia Jr. et al.
Ans: Thank you for the suggestion. We rephased the sentence into “The study from Garcia Jr. et al. stated…”
Reviewer 2 Report
Strenght. In views that coronavirus sars cov 2, enters cells via the interaction between its spike protein and angiotensin-converting enzyme 2 (ACE-2) and produce systemic inflammation and organ dysfunction by activating the NF-κB-associated inflammasome and cascade responses in immune system, the proposal is that Chronic immunosuppressive agents can disturb the immune response to the SARS-CoV-2 spike protein, specially in sick people and that multiple comorbidities and the impaired immune system is showed in renal injured patients and thus In this interesting review or explanation paper, nephrology researchers explain that the use of antimetabolites might hamper the power of neutralizing SARS-CoV-2 antibodies in those special patients. Based on some evidence, chronic kidney disease CKD patients should receive regular vaccinations
and even booster doses during the SARS-CoV-2 pandemic to improve their response to pandemia. They propose on the basis of some little evidence, the immune compromised status of CKD patients might decrease neutralizing antibody development after a single dose of a specific vaccine. According to the Open-SAFELY database from the UK, the hazard ratio for COVID-19-related death increased with the severity of CKD status researcher explain all variabilities implicated in renal injuries calcineurin inhibitors:, immunosuppressive therapies, antimetabolites, plus the higher incidence of critical illness and acute kidney injury in patients with CKD. However, as authors say, Further evidence is needed to understand the factors disturbing the immunogenicity of the SARS-CoV-2, vaccine, and CKD patients status.
Weakness 1 please check typos or mispelling in english language
2 adding some pictures or diagrams covering the topics included in the paper, could be more interesting and readable for the reader
in line 75 phrase: The risk of SARS-CoV-2 infection was high in 75 ESRD patients (15) is missing reference 15
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 3 Report
In this review the Authors report the scientific evidences about SARS-CoV2 vaccine effect in CKD, HD and KT patients. The topic is quite interesting and useful even in clinical practice.
Comments:
- In general the Authors must specify (both in the title and aim) if this is a narrative or systemic review. In the latter case, the selection criteria must be added.
- The Authors should shortly reveal in advance what is the thread of the paper in order to make the reader easy to understand (and find) the contents.
- L213 is the GC dose express in "PDN-equivalent"?
Author Response
Please see the attachment
Author Response File: Author Response.docx
Reviewer 4 Report
The manuscript is a review about the efficacy of COVID-19 vaccination in patients with chronic kidney disease (CKD) and kidney transplantation. The review brings interesting and updated information, the English is clear and understandable. Minor spelling errors and typos should be corrected, as pointed and annotated in the pdf file (attached).
Comments for author File: 
Comments.pdf
Author Response
To
Editor-in-Chief
Vaccines
Respected Sir,
Thank you for considering the manuscript, entitled “The efficacy of COVID-19 vaccines in chronic kidney disease 2 and kidney transplantation patients” by Yi-Chou Hou, et al for publication in Vaccines after revision.
First, we would like to thank the Reviewers’ for critically reviewing this manuscript and providing us many invaluable comments and suggestions. We responded to each of the reviewers’ comments and clarified/amended every necessary part raised by the reviewer. The detailed statements, reviewer-by-reviewer, and point-by-point are enclosed as following. We highly appreciate all your help and further arrangement. We hope that the revised version of the manuscript could meet the academic standard of Vaccines.
Yours truly,
Ko-Lin Kuo, MD. PhD
Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City
E-mail: [email protected]
Comments from Reviewer 4:
The manuscript is a review about the efficacy of COVID-19 vaccination in patients with chronic kidney disease (CKD) and kidney transplantation. The review brings interesting and updated information, the English is clear and understandable. Minor spelling errors and typos should be corrected, as pointed and annotated in the pdf file (attached).
ANS Thank you for valuable opinion for the thoroughly reviewing the misspelling and typos we made. We highly appreciate the reviewer’s comment and made the revision according to the reviewer’s suggest with highlight. We kindly ask the reviewer to view the revision.
Again, we deeply felt grateful for the reviewer’s comments on the manuscript. We revised and added the essential revision in order to match the comments from the reviewer and the academic standard for Vaccines.
Author Response File: Author Response.docx
Round 2
Reviewer 3 Report
None
