Assistance and Delivery of COVID-19 Vaccinations to Patients with Rare Diseases

Round 1

Reviewer 1 Report

(1) COVID-19 is not a type of flu.   They are different viruses and identified differently.

(2) Be consistent in the discussing the Brazilian National Vaccination Plan.  In the abstract it state National Vaccination Program.  In the Introduction the Plan is identified as the Brazilian National Vaccination Plan.  Under Vaccination on Page 4 it is identified National Immunization Program (PNI).  On Page 5 it states  National Plan for the Operationalization of Vaccination against COVID-19.    Are all these the same?  If not, then explain a little better the differences.  If so, then use one way of identifying the plan.

(3) The statement under Rare Disorders “There are approximately 7,000 diseases worldwide that are currently considered to be rare……..  Needs a reference.

(4) Suggest stating the objectives in a different order and organizing the narrative in the same order.  Suggest

a)    Describe the evolution of the diseases from its discovery to the mutations that followed it,

b)    Identify the procedures implemented by the National Vaccination Plan for the Brazilian population over 18 years old

c)    Analyze the care provided to rare disease patients in the Anti-COVID-19 vaccination campaign

d)    Assess the effectiveness of the plan implemented from the perspective of the “rare” person.

The way the content/narrative is currently presented it  too choppy and hard to follow given the order of objectives stated at the beginning of the manuscript.

English language was fine. 

Author Response

Dear reviewer,

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in the changes banner in the re-uploaded files.

(1) COVID-19 is not a type of flu. They are different viruses and identified differently.

• COVID-19 is an acute respiratory disease caused by SARS-CoV-2 with numerous mutations and its treatment has led to new studies and new and/or constant immunization processes.

(2) Be consistent in the discussing the Brazilian National Vaccination Plan.  In the abstract it state National Vaccination Program.  In the Introduction the Plan is identified as the Brazilian National Vaccination Plan.  Under Vaccination on Page 4 it is identified National Immunization Program (PNI).  On Page 5 it states  National Plan for the Operationalization of Vaccination against COVID-19.    Are all these the same?  If not, then explain a little better the differences.  If so, then use one way of identifying the plan.

2.1- In Brazil, the National Immunization Program (PNI), also known as the National Vaccination Plan, established on September 18, 1973, is responsible for the national immunization policy. Its mission is to reduce morbidity and mortality from vaccine-preventable diseases by strengthening integrated health surveillance actions to promote, protect, and prevent the health of the Brazilian population. The NIP is one of the largest vaccination programs in the world, nationally and internationally recognized. Within the Pan American Health Organization (PAHO), a branch of the World Health Organization (WHO), the Brazilian NIP is cited as a global reference. The PNI serves the entire Brazilian population, currently estimated at 213.3 million people, and is considered one of the assets of the Brazilian state, maintained through the commitment and dedication of healthcare professionals, managers, and the entire population. However, in response to the COVID-19 pandemic, which has been classified as a Public Health Emergency of International Concern, the National Plan for the Operationalization of COVID-19 Vaccination was created in Brazil on May 10, 2021. Its objective is to provide guidelines for a National COVID-19 Vaccination Campaign, considering the availability of vaccines, the specificities of each region in the country, and changes in the pandemic's scenario.

2.2- In the Brazilian National Immunization Program (PNI), which has been referenced worldwide due to its effectiveness and free, universal coverage, rare disease patients—people with extreme comorbidities—did not receive due deference in the vaccination

(3) The statement under Rare Disorders “There are approximately 7,000 diseases worldwide that are currently considered to be rare……..  Needs a reference.

3.1- The following references have been added:

Zurynski Y, Frith K, Leonard H, et al. Rare childhood diseases: how should we respond?. Archives of Disease in Childhood 2008;93:1071-1074.

Patricia Szajner & Timur Yusufzai. (2013) Introducing Rare Diseases. Rare Diseases 1:1.

(4) Suggest stating the objectives in a different order and organizing the narrative in the same order.  Suggest

4.1- The structure of the manuscript was adequate, following the reviewer’s instructions:

1. a) Describe the evolution of diseases from their discovery to the mutations that followed,

1. b) Identify the procedures implemented by the National Vaccination Plan for the Brazilian population over 18 years of age

1. c) Analyze the care provided to people with rare diseases in the Anti-COVID-19 vaccination campaign

d)Evaluate the effectiveness of the implemented plan from the perspective of the “rare” person.

Considering that all suggested changes were made, I present the final version of the manuscript and thank you immensely for your dedication in reviewing it. Therefore, these changes were essential for the better quality and clarity of the manuscript.

Yours sincerely,

Mariana Carvalho

Reviewer 2 Report

Dear authors,

I had the opportunity to review your, and I would like to commend you for your efforts to contribute to the field of vaccine strategy analyses. Your synthesis presents a compelling narrative; however, I have some concerns regarding the clarity and transparency of the methods underpinning your synthesis and conclusions. In this report, I will provide feedback and suggestions to enhance the quality and transparency of your manuscript.

Overall Comments: Your manuscript explores the political choices regarding the covid-19 vaccine strategy in Brazil. It is evident that a substantial effort has gone into collecting and synthesizing the available evidence. The narrative is engaging, but can improve from improvements in terms of structure, rigor and reproducibility. It is imperative that you clarify your methods better, and the structure of the remainder of the text should be announced in the introduction section.

Methods Section: The methods section should serve as the backbone of your synthesis, providing readers with a clear understanding of how you conducted your synthesis. To address this, I recommend the following:

1. Introduction to the Methods: In the beginning of the methods section, provide a concise yet comprehensive introduction that explains the rationale behind choosing a narrative synthesis approach. Why did you opt for this method as opposed to other synthesis techniques? This will help readers understand the underlying motivations for your choice.

2. Resource Identification: Clearly outline the sources you used to synthesize the evidence. Specify whether these were databases, published literature, grey literature, or any other resources. Be explicit in listing the databases or search engines used, as well as the search terms or strategies employed.

3.  

4. Data Synthesis: Elaborate on the techniques used for synthesizing the data. How were findings from different studies integrated into the narrative? Were any statistical or qualitative analyses applied, and if so, what methods were employed?

5. Quality Appraisal: If you assessed the quality of the included studies, provide information on the tools or criteria used for this assessment. Explain how this quality appraisal informed your synthesis and any potential biases associated with this process.

6. Interpretation: Clarify the process of interpreting the synthesized evidence. How were the findings integrated into the narrative, and what implications do they hold for the research question?

7. Limitations: Discuss the limitations of your synthesis methodology and how these limitations may affect the validity and generalizability of your results.

By addressing these points in your methods section, you will significantly enhance the transparency and comprehensibility of your research, thereby ensuring that readers can fully appreciate the rigor of your synthesis process.

In conclusion, your manuscript presents an interesting narrative synthesis. However, improving the clarity and transparency of the methods section is essential for the broader research community to understand how you arrived at your conclusions. I encourage you to carefully consider these suggestions and make the necessary revisions to strengthen your manuscript.

Thank you for considering my feedback, and I look forward to seeing the improved version of your manuscript.

Just double check for interpunction (e.g. use " " for citing individuals).

Author Response

Dear reviewer,

Thank you very much for taking the time to review this manuscript. Please find the detailed responses below and the corresponding revisions/corrections highlighted/in the changes banner in the re-uploaded files.

General Comments: Your manuscript explores political choices regarding the Covid-19 vaccine strategy in Brazil. It is clear that a substantial effort was made in collecting and synthesizing the available evidence. The narrative is engaging, but could improve with improvements in terms of structure, rigor and reproducibility. It is essential that you clarify your methods better, and the structure of the rest of the text must be announced in the introduction section.

Methods Section: The methods section should serve as the backbone of your synthesis, providing readers with a clear understanding of how you conducted your synthesis. To resolve this, I recommend the following:

Introduction to the Methods: In the beginning of the methods section, provide a concise yet comprehensive introduction that explains the rationale behind choosing a narrative synthesis approach. Why did you opt for this method as opposed to other synthesis techniques? This will help readers understand the underlying motivations for your choice.

Resource Identification: Clearly outline the sources you used to synthesize the evidence. Specify whether these were databases, published literature, grey literature, or any other resources. Be explicit in listing the databases or search engines used, as well as the search terms or strategies employed.

Data Synthesis: Elaborate on the techniques used for synthesizing the data. How were findings from different studies integrated into the narrative? Were any statistical or qualitative analyses applied, and if so, what methods were employed?

Quality Appraisal: If you assessed the quality of the included studies, provide information on the tools or criteria used for this assessment. Explain how this quality appraisal informed your synthesis and any potential biases associated with this process.

Interpretation: Clarify the process of interpreting the synthesized evidence. How were the findings integrated into the narrative, and what implications do they hold for the research question?

Limitations: Discuss the limitations of your synthesis methodology and how these limitations may affect the validity and generalizability of your results.

    Response:

A detailed methodology was included in the manuscript:

In order to conduct a comprehensive systematic documentary review of scientific and public health evidence, various data sources were employed, including academic data-bases, government official documents, technical reports, and grey literature. Primary data sources encompassed PubMed, Scopus, Web of Science, Google Scholar, the Virtual Health Library (BVS), websites of the Ministry of Health of Brazil, and specialized organizations' websites dedicated to rare disease patients. The search strategy was designed in accord-ance with the research objectives, entailing a combination of descriptors and relevant Boolean operators. Descriptors such as "COVID-19," "vaccination," "rare diseases," "Na-tional Vaccination Plan," "mutations," and others related to the research were used. The search strategy was adapted for each specific data source.

Inclusion criteria consisted of studies describing the evolution of COVID-19 from its discovery to subsequent mutations, documents identifying procedures implemented by the National Immunization Program for the Brazilian population aged over 18 years, re-ports analyzing the care provided to rare disease patients during the Anti-COVID-19 vac-cination campaign, and studies evaluating the effectiveness of the plan from the perspec-tive of individuals with rare diseases. Exclusion criteria encompassed studies or docu-ments unrelated to the research objectives, duplicated publications, and works lacking full accessibility.

For literature selection, two independent reviewers conducted the initial screening of studies and documents based on the inclusion and exclusion criteria. Disagreements were resolved through consensus, or in cases of persisting discrepancies, a third reviewer in-tervened. The quality of the included studies was assessed using specific criteria tailored to each study type. For non-academic documents, such as government reports, a credibil-ity and relevance assessment were conducted by two independent reviewers. Relevant data from each study/document were extracted and organized into a database, incorpo-rating information about disease evolution, vaccination procedures, care for rare disease patients, and evaluation of vaccination plan efficacy.

    Heterogeneity among studies/documents was evaluated, taking into consideration differences in study populations, methodologies, and outcomes. Substantial heterogeneity was addressed during qualitative analysis. The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) scale, considering criteria of quality and result consistency (GUYATT et al., 2008). Re-garding study limitations, non-academic documents may have limitations in terms of methodology and statistical analysis, which can influence the quality of evidence, and the focus on the Brazilian perspective may limit the generalization of results.

    Guyatt, GH, Oxman, AD, Vist, GE, Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., ... & Schünemann, HJ (2008). GRADE: um consenso emergente sobre a classificação da qualidade das evidências e a força das recomendações. BMJ, 336(7650), 924-926.

Considering that all suggested changes were made, I present the final version of the manuscript and thank you immensely for your dedication in reviewing it. Therefore, these changes were essential for the better quality and clarity of the manuscript.

Yours sincerely,

Mariana Carvalho

Reviewer 3 Report

Overall, this article promotes knowledge and I agree with this format

Author Response

Reviewer 3

Dear Reviewer,

Thank you very much for taking the time to review this manuscript, the changes suggested by the other reviewers were made, therefore, I present the final version of the manuscript and thank you immensely for your dedication in reviewing it. These changes were essential for the better quality and clarity of the manuscript.

Yours sincerely,

Mariana Carvalho

Round 2

Reviewer 2 Report

Dear authors,

Thanks for this revision. The text has definitely improved in terms of clarity. Yet, I would like to suggest the following changes:

- Introduction section: this has become very long- please summarize this.

- Lines 54-66: please clarify that your research pertains in particular the situation in Brazil.

- Line 56-58: "Describe the evolution of the disease from its discovery to the mutations that followed it." This is a rather generic statement and is not a goal of this research as such. Please omit this section.

Although the English is definitely comprehensible, the manuscript would benefit from a proof read by a native speaker; mainly for improvements in term of flow. Furthermore, as I outlined above, the introduction section should be shorter.

Author Response

Dear Reviewer,

Thank you very much for your positive evaluation regarding the improvements to the manuscript and for contributing even more to the final text.

Introduction section: this has become very long- please summarize this.

Response:

The introduction was summarized maintaining the context, importance of the research and its objectives. However, in order to maintain the clarity of the methodological stage as requested by the reviewers, a topic of materials and methods was added.

- Lines 54-66: please clarify that your research pertains in particular the situation in Brazil.

- Line 56-58: "Describe the evolution of the disease from its discovery to the mutations that followed it." This is a rather generic statement and is not a goal of this research as such. Please omit this section.

Response:

The text has been adjusted as follows:

The aim of this study is to conduct a critical analysis, focusing on the procedures of the National Immunization Program for the Brazilian population aged over 18, the care provided to individuals with rare diseases during the anti-COVID-19 vaccination campaign, and the evaluation of the plan's effectiveness from the perspective of individuals with rare diseases in Brazil.

Comments on the Quality of English Language

Although the English is definitely comprehensible, the manuscript would benefit from a proof read by a native speaker; mainly for improvements in term of flow. Furthermore, as I outlined above, the introduction section should be shorter.

Response:

I inform you that the English has been revised as per the data below:

We certify that the following article COVID-19 VACCINATION HOW THE ASSISTANCE TO THE PATIENT OF RARE DISEASE WAS DELIVERED Mariana Carvalho de Moraes *, Ivone Duarte, Rui Nunes has undergone English language editing by MDPI. The text has been checked for correct use of grammar and common technical terms, and edited to a level suitable for reporting research in a scholarly journal. MDPI uses experienced, native English speaking editors. Full details of the editing service can be found at ► https://www.mdpi.com/authors/english.

Yours sincerely,

Mariana Carvalho