Review Reports - Effect of Distress, Anxiety, and Depressive Symptoms on SARS-CoV-2 mRNA BNT162b2 Vaccine Efficacy in Cancer Patients

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Prospective, observational cohort study to assess the antibody titer reactogenicity to 30 μg of BNT162b2-SARS-COV-2 vaccine in cancer patients on active treatment. In the evaluated 218 cancer patients, besides age metastatic disease stage and high distress were the only independent significant variables. In addition, the possible nocebo effects of SARS-COV-2 vaccine should be discussed.

Author Response

Reviewer 1:

Comments and Suggestions for Authors

Authors: Thank you for your comment, we have included a brief discussion of the possible nocebo effect within the discussion.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review the manuscript "

Effect of distress, anxiety and depressive symptoms on SARS-2 CoV-2 mRNA BNT162b2 vaccine efficacy in cancer patients. "

The study is particularly interesting because it involves a population of people who are difficult to study.

There are some important issues that the authors need to address before the manuscript can be considered for publication.

Below are my comments describing these issues.

1. Introduction

Line 56-61 These sentences are more appropriate for inclusion in the Materials and Methods section.

Authors should focus on the topic of their work in the introduction rather than describe the research they have conducted. Please correct it.

2. Materials and Methods

Please provide information about the study group, including details about when the study was conducted. Additionally, outline the inclusion and exclusion criteria for the study. Present this information in a diagram and relocate it from Supplemental Figure 1 to the Materials and Methods section.

3. Results

Line 169-170 – This sentence is more appropriate for inclusion in the Materials and Methods section.

Line 170- 290 were assessable at 42 days and 218 at 6 months, as shown in the CONSORT statement in Supplemental Figure 1.

However, in Supplemental Figure 1. there are 291 subjects. Please explain this.

And in the abstract, there are also 291 subjects.

Please correct and explain it.

In the results section, the authors should place a table or figures after the description of the results, then the results would be more transparent.

Line 187- The authors describe individuals who smoke cigarettes, but this group is not mentioned in the materials and methods, nor is it included in Table 1, which outlines the characteristics of the study participants.

Please correct and explain it.

Line 207- Please describe the abbreviations used in table 2 below the table

4. Discussion

Line 226-230- These sentences are more appropriate for inclusion in the Materials and Methods section.

Line 243- The sentence should not begin with the words "for example”.

Line 245-246- This has already been discussed in the introduction.

Line 265-270- Please add references.

In the discussion, please reference studies by other authors regarding vaccinations against SARS-CoV-2 in patients with cancer.

In the manuscript, avoid referring to your previous research unless absolutely necessary.

Author Response

Reviewer 2:

Comments and Suggestions for Authors

Thank you for the opportunity to review the manuscript.

Effect of distress, anxiety and depressive symptoms on SARS-2 CoV-2 mRNA BNT162b2 vaccine efficacy in cancer patients. "

The study is particularly interesting because it involves a population of people who are difficult to study. There are some important issues that the authors need to address before the manuscript can be considered for publication.

Below are my comments describing these issues.

Introduction

Line 56-61 These sentences are more appropriate for inclusion in the Materials and Methods section.

Authors: done.

Authors should focus on the topic of their work in the introduction rather than describe the research they have conducted. Please correct it.

Authors: done.

Materials and Methods

Please provide information about the study group, including details about when the study was conducted. Additionally, outline the inclusion and exclusion criteria for the study.

Authors: done.

Present this information in a diagram and relocate it from Supplemental Figure 1 to the Materials and Methods section.

Authors: done.

Results

Line 169-170 – This sentence is more appropriate for inclusion in the Materials and Methods section.

Authors: done.

Line 170- 290 were assessable at 42 days and 218 at 6 months, as shown in the CONSORT statement in Supplemental Figure 1.

Authors: done.

However, in Supplemental Figure 1. there are 291 subjects. Please explain this.

Authors: done.

And in the abstract, there are also 291 subjects. Please correct and explain it.

Authors: done.

In the results section, the authors should place a table or figures after the description of the results, then the results would be more transparent.

Authors: done.

Line 187- The authors describe individuals who smoke cigarettes, but this group is not mentioned in the materials and methods, nor is it included in Table 1, which outlines the characteristics of the study participants. Please correct and explain it.

Authors: We deleted this section of smoking since it was previously pubblished in the first paper in European Journal of Cancer.

Line 207- Please describe the abbreviations used in table 2 below the table

Authors: done.

Discussion

Line 226-230- These sentences are more appropriate for inclusion in the Materials and Methods section.
Line 243- The sentence should not begin with the words "for example”.
Line 245-246- This has already been discussed in the introduction.
Line 265-270- Please add references.
In the discussion, please reference studies by other authors regarding vaccinations against SARS-CoV-2 in patients with cancer.
In the manuscript, avoid referring to your previous research unless absolutely necessary.

Authors: thanks for the suggestions we have improved the text.

Reviewer 3 Report

Comments and Suggestions for Authors

This paper investigates the association between mental health (depression and anxiety) and COVID-19 vaccine efficacy in cancer patients (N=218). The authors used multivariable regression with a mixed effects model. The results indicate a significant correlation between the variables of interest. The implications of this study are important, emphasizing the effect of mental health on vaccine efficacy, particularly for those with pre-existing conditions.

Overall, this paper presents valuable findings with appropriate analytical tools, and the presentation is generally well done. However, there are some concerns that need to be addressed to improve the quality of the manuscript.

Major Concerns

1. Discrepancy in Participant Numbers in Table 1 and Supplementary Figure 1: Table 1 indicates that there were 219 participants in the study, while Supplementary Figure 1 shows 291 participants at 42 days and 218 at 6 months. Although this discrepancy might seem minor, it is important to address this inconsistency to avoid confusion.

2. (Optional) Consideration of Hazard Ratio (Cox Regression): While the statistical analysis in the paper is robust, there might be an omitted effect due to survival bias. The authors may want to consider using Cox regression to account for participants who passed away before the 6-month time point. Alternatively, the authors could justify or confirm that the 37 deaths were not COVID-19 related, thereby eliminating the possibility of survival bias.

Minor Concerns

1. Inconsistent Plot: It appears that ggplot from R was used to generate the plots. Please ensure consistency in the plot themes throughout the manuscript. Some plots have a grey background (e.g., Supplemental Fig 2), while others use themes like `theme_minimal` or `theme_classic` (e.g., Fig 1). Consistent formatting will improve the visual presentation of the paper.

2. Potential Overclaim in the Second-to-Last Paragraph: Specifically, lines 282-284 state, "Our study indicates that current and former smokers …" This statement seems to reference findings from a previous study rather than the results of this study. The authors should clarify the source of this statement to avoid overclaiming and ensure accuracy.

Author Response

Reviewer 3:

Comments and Suggestions for Authors

Major Concerns

Discrepancy in Participant Numbers in Table 1 and Supplementary Figure 1: Table 1 indicates that there were 219 participants in the study, while Supplementary Figure 1 shows 291 participants at 42 days and 218 at 6 months. Although this discrepancy might seem minor, it is important to address this inconsistency to avoid confusion.

Authors: done.

(Optional) Consideration of Hazard Ratio (Cox Regression): While the statistical analysis in the paper is robust, there might be an omitted effect due to survival bias. The authors may want to consider using Cox regression to account for participants who passed away before the 6-month time point. Alternatively, the authors could justify or confirm that the 37 deaths were not COVID-19 related, thereby eliminating the possibility of survival bias.

Authors: We appreciate the reviewer’s suggestion regarding survival bias. We confirm that the 37 participants lost to follow-up before the 6-month time point did not pass away due to COVID-19. Therefore, survival bias related to COVID-19 does not impact our findings.

Minor Concerns

Inconsistent Plot: It appears that ggplot from R was used to generate the plots. Please ensure consistency in the plot themes throughout the manuscript. Some plots have a grey background (e.g., Supplemental Fig 2), while others use themes like `theme_minimal` or `theme_classic` (e.g., Fig 1). Consistent formatting will improve the visual presentation of the paper.

Authors: done.

Potential Overclaim in the Second-to-Last Paragraph: Specifically, lines 282-284 state, "Our study indicates that current and former smokers …" This statement seems to reference findings from a previous study rather than the results of this study. The authors should clarify the source of this statement to avoid overclaiming and ensure accuracy.

Authors: done.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your thorough correction of the manuscript.

I have a question regarding the paragraph in the discussion on lines 226-230 (now 243-248). Is it necessary to repeat this paragraph, as it has already been explained in the Materials and Methods section?

Author Response

Comments 1: I have a question regarding the paragraph in the discussion on lines 226-230 (now 243-248). Is it necessary to repeat this paragraph, as it has already been explained in the Materials and Methods section?

Response 1: Thank you for your comment. You are absolutely right; it results in repetition. We have removed the paragraph.

Reviewer 3 Report

Comments and Suggestions for Authors

Thank you for your response. All comments have been addressed. The supplement Figure 1 still has some paragraph marks. Please fix it and I think it is ready to go

Author Response

Comments: Thank you for your response. All comments have been addressed. The supplement Figure 1 still has some paragraph marks. Please fix it and I think it is ready to go.

Response: Thank you for your comment, we have corrected Supplemental Figure 1.