COVID-19 Vaccine in Inherited Metabolic Disorders Patients: A Cross-Sectional Study on Rate of Acceptance, Safety Profile and Effect on Disease

Round 1

Reviewer 1 Report

Thanks for the opportunity to review this paper. This study was investigated “COVID-19 vaccine in inherited metabolic disorders patients: 2 rate of acceptance, safety profile and effect on disease”. This manuscript is well written, organized and interesting study. This study investigate COVID-19 vaccine  practice in inherited metabolic disorders.  This manuscript should be reorganized according to recommended revisions.

 

Major revisions:

-       Title of this study should be changed according to study results. 

-       Abstract section should be rewritten. In this section, the data about the study should be given numerically, detailed and much general information should be extracted.

-       Introduction section should be elaborated.  The objective of this study should be clearly explained. 

-       Material-methods section should be detailed and divided to subheadings. 

-       Power analysis should be calculated for this study. 

-       Results section should be specified.  This section should be divided to subheadings. This section is quite complicated, it should be simplified. 

-       Authors should be described astasia abasia. 

-       Statistical methods should be checked especially parametric and nonparametric values. Percentage and numerical values should be given consecutively

-       Discussion and conclusion section should be specified. Conclusion part of discussion should be added. 

-       Diagnostic limitations of this study should be summarized in discussion section. 

 

Minor revisions should be done in this study.  

-        References section should be updated. References section should be written according to the rules. Authors should be cited this references. 

§  Özalp Akın E et al. Unmet needs of children with inherited metabolic disorders in the COVID-19 pandemic. Turk Arch Pediatr. 2022;57(3):335-341.

§  Haslak F et al.  Early experience of COVID-19 vaccine-related adverse events among adolescents and young adults with rheumatic diseases: A single-center study. Int J Rheum Dis. 2022 Mar;25(3):353-363. PMID: 34978376.

 

-        All abbreviations should be summarized in this manuscript.  

-        The keywords should be added by the alphabetical order

-        There are numerous spelling mistakes in the manuscript and reference section. These must be corrected. 

-        Table headings should be more informative.

-        Manuscript should be reorganized according to journal rules. 

 

 

 

 

Author Response

Major revisions

 

- Title of this study should be changed according to study results.

R. The information given in the title, relate to the main study results, we have added the type of study “cross-sectional study” to clarify the method used for the analysis.

 

- Abstract section should be rewritten. In this section, the data about the study should be given numerically, detailed and much general information should be extracted

 

R.Many thanks for this observation, allowing us to improve this section. Abstract was rewritten and numerical data, also according to types of disorders, were added.

 

- Introduction section should be elaborated. The objective of this study should be clearly explained.

R. This section was re-elaborated and English language style improved. Objective of our study was rewritten and more circumstantiated.

 

- Material-methods section should be detailed and divided to subheadings.

R. This section was divided into two sections according with the content: study design and statistical analysis

- Power analysis should be calculated for this study

R. A sample size of 174 subjects has a study power of 0.86, alfa error: 0.05. Now it is included in the text.

- Results section should be specified. This section should be divided to subheadings. This section is quite complicated, it should be simplified.

R: The section “Results”, is divided into 5 subheadings (see text). We have semplified the text, increasing the referral to tables and figures and giving more details to the data reported. We hope this may result in improvement of clarity and readability.

- Authors should be described astasia abasia.

R. Authors contribution was rewritten.

 

-Statistical methods should be checked especially parametric and nonparametric values. Percentage and numerical values should be given consecutivel

R. In the “Statistical Analysis” section, we specified the tests used: “Differences in continuous variables between groups were compared using a Student’s t-test for normally distributed parameters, or nonparametric Mann-Whitney U Test in case of non normal distribution”.

-Discussion and conclusion section should be specified. Conclusion part of discussion should be added.

R. The section “Conclusion” has been added and text implemented.

-Diagnostic limitations of this study should be summarized in discussion section.

R. We have further expanded on the limitations of the study, also secondary to the type of investigation (cross-sectional study). We have also added some strenghs of the study.

 

 

Minor revisions should be done in this study.

 

- References section should be updated. References section should be written according to the rules.

R. References have been updated and written according to the journal style.

 

- Authors should be cited this references.

• Özalp Akın E et al. Unmet needs of children with inherited metabolic disorders in the COVID-19 pandemic. Turk Arch Pediatr. 2022;57(3):335-341.
• Haslak F et al. Early experience of COVID-19 vaccine-related adverse events among adolescents and young adults with rheumatic diseases: A single-center study. Int J Rheum Dis. 2022 Mar;25(3):353-363. PMID: 34978376.

R. The above references have been contextualized and added.

 

- All abbreviations should be summarized in this manuscript.

R. Done

- The keywords should be added by the alphabetical order

R. Done

 

- There are numerous spelling mistakes in the manuscript and reference section. These must be corrected.

R. The manuscript was throughly checked and spelling mistakes corrected.

 

- Table headings should be more informative.

R. We have added more details in the table and figures headings, thank you.

 

-       Manuscript should be reorganized according to journal rules.

R. For this manuscript, we have followed the journal rules, accessed at: https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijerph/instructions

 

Reviewer 2 Report

Reviewer’s comments on Manuscript IJERPH- 1869236

Title: COVID-19 vaccine in inherited metabolic disorders patients: 2 rate of acceptance, safety profile, and effect on disease

General Comment

The work utilized a cross-sectional telephone-based survey to understand the vaccination hesitancy towards the COVID-19 vaccine, the reasons for hesitancy, and the adverse effects among patients with Inherited Metabolic Diseases. The authors should please employ the assistance of a native English-speaking colleague or English language editing services to enhance readability.

Abstract:

1.       Please remove the numberings

2.       Line 11- significantly impact? Please explain how. Had the covid 19 vaccine reduced the spread or incidence of the disease?

3.       Line 21- Can we have data for both” Local (%) and systemic (%) effects were equally reported after the first dose

4.       Line 26: “effectively contrast hesitancy” What do you mean by this?

Introduction:

5.       Line 35- “avoided” replace with “prevented”

6.       Line 39 “million” replace with “millions”

7.       Line 42- you mean “pregnant”

8.       Line 46- these disease “s” remain unvaccinated

9.       Line 49- delete “fragile” and replace it with “immunocompromised”

10.   Lines 50-51- please rephrase.  It was free of cost and, in Apulia Region was managed in referral Hospitals????

11.   Line 58- “among a cohort of IMD patients” delete “a cohort of”. Let this just read among IMD patients

Materials and Methods

12.   Can the authors provide details of the study area?

13.   Line 63- how long did the phone interviews take? Why the choice of a telephone interview and not the use of other options?

14.   Your data analysis section is completely missing. Provide details of the data collected were managed and analyzed. A comparison of the rate of systemic reactions with that of the general population was conducted how. And what is the basis for this comparison?

15.   Lines 85-86- Please the authors should provide detailed documentation of the ethical approval for this work. Provide the name of the local ethic committee, city, town, province if applicable, the reference number, etc. Was any witness present when consent was obtained verbally?  Was anyone needing parental consent included in the study? If yes, this must be stated and how. I can see that the minimum age included in the study is 12.1 years.

Results

16.   Line 92 please report min and max values instead of range median age was 23.4 years (min.---. Max…) 12.1-61.7)

17.   Line 106 please specify these other IMDs

18.   Table 2 Why did you have reduced responses (total number of participants) to Types of vaccines and Adverse reactions to vaccines?

19.   Lines 120-121. Please rephrase the sentence for clarity.

20.   FANS meaning??

21.   Figure 1- produce an image with a better resolution

22.   Figure 2 missing

23.   Line 170-172. How were there comparisons performed? Why the choice of “young healthy adult subjects”? Considering you had minors in your study.

Discussion

24.   Lines 196 -204. Avoid repeating results or findings in the Discussion section. Please move to the appropriate section

 

25.   How do these studies relate to your findings? Tsai et al. and JK Gordon et al. 

6. you need to support your critical findings with what others have done

 

Author Response

Abstract:

 

Please remove the numberings

R. Numbering removed from the abstract section,

Line 11- significantly impact? Please explain how. Had the covid 19 vaccine reduced the spread or incidence of the disease?

R. Reducing the numbers of new infections and of deaths in several countries, this sentence has been added in the text.

Line 21- Can we have data for both” Local (%) and systemic (%) effects were equally reported after the first dose

R. The relative percentages are 51% vs 52%. Anyway, responding also to the other reviewers comments, we rewrote this part of the abstract and we decided to eliminate this data which was not enough clear.

Line 26: “effectively contrast hesitancy” What do you mean by this?

R. In many cases we had to talk with patients, actively explaining the “real” risks linked to the vaccine, distinguishing them from what patients had heard or read on websites

Introduction:

Line 35- “avoided” replace with “prevented”

R. Done

Line 39 “million” replace with “millions”

R. Done

Line 42- you mean “pregnant”

R. Corrected

Line 46- these disease “s” remain unvaccinated

R. Corrected

Line 49- delete “fragile” and replace it with “immunocompromised”

R. The concept of “fragility” has a general meaning, not just linked to the immunocompromission. For clarity, we eliminated this objective, making just reference to what is later written “affected by genetic and/or chronic conditions”

Lines 50-51- please rephrase.  It was free of cost and, in Apulia Region was managed in referral Hospitals????

R. We rewrote this sentence as follows: “It was free of cost in Apulia Region where it was managed in referral Hospitals”.

Line 58- “among a cohort of IMD patients” delete “a cohort of”. Let this just read among IMD patients

R. Done

 

Materials and Methods

Can the authors provide details of the study area?

R. The study centre is the referral centre for Apulia and Basilicata Regions (South Italy). We have specified this in the text.

Line 63- how long did the phone interviews take? Why the choice of a telephone interview and not the use of other options?

R. Each telephone interviews lasted about 20-30 minutes, we decide to use this methodology, instead of online questionnaires to reduce the self-reporting bias. We have clarified this in the Discussion section.

Your data analysis section is completely missing. Provide details of the data collected were managed and analyzed. A comparison of the rate of systemic reactions with that of the general population was conducted how. And what is the basis for this comparison?

R: Many thanks for this observation, the statistical analysis section has been added, with the tests used for the inferential statistics. The comparison of the rate of systemic reactions in our sample with that of the general population was performed using Chi-square test. It is specified in the text.

Lines 85-86- Please the authors should provide detailed documentation of the ethical approval for this work. Provide the name of the local ethic committee, city, town, province if applicable, the reference number, etc. Was any witness present when consent was obtained verbally?  Was anyone needing parental consent included in the study? If yes, this must be stated and how. I can see that the minimum age included in the study is 12.1 years.

R. Ethic commettee of Azienda Ospedaliero-Universitaria Policlinico of Bari, Bari, Apulia Region, Italy. Protocol number registration: 73656.

For patients aged between 12 and 18 years, consent was obtained both from patients and parents. We have stated that in the text.

Results

Line 92 please report min and max values instead of range median age was 23.4 years (min.---. Max…) 12.1-61.7)

R. We have now replaced “range” with “min-max”. Thanks.

Line 106 please specify these other IMDs

R. The “other IMDs” have been specified and reported under Table 1.

Table 2 Why did you have reduced responses (total number of participants) to Types of vaccines and Adverse reactions to vaccines?

R. The total number of partecipants to the study was 174, of them 163 (94%) received at least one dose of vaccine and on this number were calculated percentages for types of vaccine and adverse reaction

Lines 120-121. Please rephrase the sentence for clarity. The second dose was not given for the following reasons: COVID-19 infection after the first dose (n = 4) or second dose expected after our interview (n = 8) (lines 129-131)

R. The sentence was rephrased according with the above suggestion.

FANS meaning?? non-steroidal anti-inflammatory drugs

R. We have now replaced FANS with NSAIDs. Thanks for that.

Figure 1- produce an image with a better resolution

R. We have added an image with improved resolution.

Figure 2 missing

R. It is now reported.

Line 170-172. How were there comparisons performed? Why the choice of “young healthy adult subjects”? Considering you had minors in your study.

R. We explained the tests used in the statistical analysis section, as described in the answer to question 14. Studies on young healthy subjects were chosen for two reasons: first, the majority of highly impacted evidences available and on a high number of partecipants, come from vaccine on young adults; second, in spite of a wide age range (12.1-61.7 years) the vast majority of our patients were young adults (76 subjects aged between 20 and 30 years) as demonstrated by their median age: 23.4 years. We have specified that in the text.

 

Discussion

Lines 196 -204. Avoid repeating results or findings in the Discussion section. Please move to the appropriate section

R. We have removed the summary of results from the “Discussion” section.

How do these studies relate to your findings? Tsai et al. and JK Gordon et al. 

 R. To the best of our knowledge, there are no other studies on effects of COVID-19 vaccine in IMDs (reported in the text) therefore we had to relate to other chronic conditions of which there were enough evidences, to contextualize and give support to our results.

you need to support your critical findings with what others have done

R. Please, refer to the above answer.

Round 2

Reviewer 1 Report

All corrections and revisions are appropriate for me. 

Author Response

Many thanks for your comments. The authors

Reviewer 2 Report

I am presently satisfied with the authors' responses. However, the authors must attend to a few minor comments in the manuscript text. The manuscript will need moderate English language editing

Author Response

Many thanks for your suggestion, we performed a deep language revision, to improve English style. We hope it is sufficient to make the manuscript acceptable. The authors