Dear Dr. Ghazy,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: No comment

==============================

Please submit your revised manuscript by Oct 26 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

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Stephen Dajaan Dubik, BSc, MPH, MPhil

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Dear Authors,

This is an interesting paper. I have the following comments

1) Kindly define the outcome terms in methods section - example normal fear/extreme fear. What do they mean? What were their cut-offs? How did you come to that

2) What is good confidence/intermediate/poor confidence

Most of your results and discussion are from these outcomes. It will be useful for the reader to understand it.

Hope these comments are useful

Reviewer #2: This cross-national study titled ‘Cross-National Disparities in Healthcare Workers' Perceptions: Examining Fear of Infection and Confidence in COVID-19 Vaccines in the Context of Emerging Variants’ examined healthcare workers' (HCWs) perceptions of COVID-19 infection fear and vaccine confidence in the context of emerging variants. The research involved 5,843 HCWs from various global regions, with a mean age of 32.1 years. Data was collected through online surveys and face-to-face interviews between November 1 and December 5, 2023, using validated scales to assess fear levels and vaccine confidence. The study sample was diverse, with 42.5% of participants from the Eastern Mediterranean Region, 24.2% from the African Region, 14.4% from Western countries, and 18.9% from other world regions. A majority (72.8%) of participants were vaccinated, with Pfizer, AstraZeneca, and Sinopharm being the most common vaccines received.

Results indicated that a significant portion of HCWs experienced fear related to COVID-19, with 30.4% feeling uncomfortable and 28.4% fearing for their lives. However, 35.3% of participants demonstrated good attitudes and confidence towards the vaccine. Factors associated with higher vaccine confidence included older age, male gender, presence of chronic and mental disorders, larger family size, and previous COVID-19 infection. Conversely, concerns about side effects were linked to lower vaccine confidence. The study revealed regional differences in attitudes towards the COVID-19 vaccine among HCWs, so the authors concluded that targeted educational programs should be implemented to address uncertainties and promote widespread vaccine acceptance among healthcare workers. These findings provide valuable insights for developing strategies to enhance vaccine confidence and address fears among HCWs in different global regions.

I think the idea of this article may be of interest to the readers of Plos One. However, some comments, as well as some crucial evidence that should be included to support the authors’ argumentation, needed to be addressed to improve the quality of the manuscript, its adequacy, and its readability prior to the publication in the present form. My overall judgment is to publish this research article after the authors have carefully considered my suggestions below, in particular reshaping parts of the Introduction and Methods sections by adding more evidence.

Strengths:

• Large, diverse sample size (5,843 healthcare workers) across multiple regions provides good statistical power and cross-national comparisons.

• Use of validated scales to measure fear (FCS) and vaccine confidence (ARAB-VAX-CONF) strengthens the reliability of the findings.

Please consider the following comments:

• The introduction should provide more background on the emergence of new COVID-19 variants and their potential impact on healthcare workers' perceptions and behaviors. In my opinion, this is crucial for understanding the study's relevance.

• A brief review of previous studies on healthcare workers' attitudes towards COVID-19 vaccines and their fears related to infection would be beneficial, as this would help establish the current state of knowledge and identify gaps this study aims to fill. Additionally, the authors could strengthen the rationale for their study by explaining why understanding healthcare workers' perceptions is particularly important in the context of emerging variants.

• The authors may consider incorporating a brief discussion on the potential neural substrates underlying fear responses and vaccine confidence among healthcare workers. Recent neuroimaging studies have identified brain regions involved in processing fear and anxiety, such as the amygdala, insula, and prefrontal cortex, which could be relevant to understanding the neurobiological basis of COVID-19 related fears. Additionally, exploring the neural correlates of decision-making processes related to vaccine acceptance could provide valuable insights. Including this perspective could strengthen the paper's theoretical framework and suggest directions for future research combining psychological and neuroscientific approaches to vaccine hesitancy among healthcare professionals [1-3].

• The manuscript lacks details on how participants were recruited across different regions. More information is needed on the sampling method and how representativeness was ensured.

• While they mention both online surveys and face-to-face interviews were used, authors have provided no explanation of how face-to-face interviews were conducted safely during the pandemic. The process for distributing the online survey is also not described: authors should provide more details on this.

• The methods section does not describe any statistical analysis techniques used to analyze the data. This is a significant omission.

• There's no mention of statistical tests performed or p-values to indicate the significance of the findings.

• The results don't address potential confounding factors that could influence fear levels or vaccine confidence among healthcare workers.

• The discussion would benefit from comparing these findings to other relevant studies on healthcare worker vaccine confidence and fear levels during the pandemic.

• While regional differences are mentioned, there's minimal exploration of potential reasons behind these disparities. I would suggest expanding on this point.

• The conclusions could be strengthened with more specific recommendations for practice and policy based on the findings.

References:

1. https://doi.org/10.1038/s41398-020-01150-4

2. https://doi.org/10.1111/acps.13602

3. DOI: 10.3390/biomedicines12051083

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

**********

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Dear Dr. Ghazy,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 03 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Stephen Dajaan Dubik, BSc, MPH, MPhil

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

**********

Reviewer #2: Dear Authors,

Thank you for the opportunity to review your manuscript. I appreciate the thorough and detailed responses to the comments I have raised in the precedent revision. It is evident that you have carefully considered the feedback and made significant improvements to the manuscript.

Below, I provide a summary of the changes and my responses to each of the comments.

• The study claims broad representation across various regions; however, clarifying the sampling method (e.g., were the samples proportionate to the healthcare workforce distribution?) would strengthen claims of cross-national comparison. Additionally, authors should specify why certain countries or regions may have lower representation could provide context for the sampling limitations.

• Since the authors report a correlation between mental health issues and vaccine hesitancy, additional context on how mental health was assessed or any screening tools used might be useful.

• The discussion might benefit from a more cautious interpretation of causality in observed relationships (e.g., family size, personal COVID-19 history) with vaccine confidence and fear. Since this is a cross-sectional study, it might be helpful to remind readers that causation cannot be firmly established.

• Although some limitations are implied, I recommend adding a dedicated limitations section discussing potential biases (e.g., self-reported data, convenience sampling) and limitations in the survey's cross-sectional design for a complete discussion.

In conclusion, the revisions made to the manuscript have significantly strengthened the quality and rigor of the work.

I commend the thoroughness of your responses and the attention to detail in addressing the concerns raised. The manuscript is now well-positioned for potential publication.

Sincerely,

Reviewer

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #2: No

**********

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

Dear Dr. Ghazy,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Apr 11 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Jennifer Tucker, PhD (Associate Editor, PLOS One) on behalf of

Stephen Dajaan Dubik, BSc, MPH, MPhil

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

Dear Dr. Ghazy,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Mona Gamal Mohamed

Academic Editor

PLOS ONE

Additional Editor Comments:

Dear Authors,

Thank you for your submission. Your study explores an important topic, but several key areas require revision to improve clarity, methodological rigor, and overall impact. Below are my detailed comments:

Title Revision: Please revise the title to include “…amid Emerging Variants” to better reflect the evolving pandemic context.

Introduction Restructuring: The introduction is too long and lacks coherence. Some sections include information that is not directly relevant to the study. Please restructure this section to ensure a logical flow and conciseness.

Sample Selection Bias: The study relies on a convenience sample of HCWs with internet access, which may introduce selection bias, particularly in regions with limited connectivity. Please discuss this limitation and explain any measures taken to mitigate its impact.

Data Collection Tools: This section should be more concise. Move detailed survey questions to an appendix and minimize descriptions of previously validated scales, referring instead to original sources.

Questionnaire Language: Clarify whether the questionnaire was administered in English across all countries. If so, discuss potential limitations for non-native speakers.

Results Section Revision: Given the large number of tables and figures, consider moving sociodemographic characteristics to a supplementary file. Additionally, refine the narrative to avoid excessive repetition of data already presented in the tables.

Sample Representativeness: The rationale for selecting specific countries is unclear. Please clarify why these countries were chosen and assess whether the sample represents the broader HCW population in each country based on demographics such as gender, age, and occupation.

Multivariate Analysis: The analysis does not appear to adjust for country-level differences, which may be a confounding factor. Given the diversity of the countries studied, it is crucial to account for these variations in attitudes toward vaccination. Please consider adjusting for country in the analysis.

Discussion Section Restructuring: The discussion is lengthy and difficult to follow. Structuring it into clear subsections will improve readability and enhance the clarity of your key findings.

Additionally, there is an interesting contrast between your findings and existing literature on vaccine hesitancy in the general population. Studies such as Dumitra et al. identify vaccine refusal primarily due to perceived lack of necessity or belief in natural immunity, while your study suggests that prior COVID-19 infection and vaccine side effects were associated with lower vaccine confidence among HCWs. This difference may be due to professional exposure, firsthand experience with COVID-19 severity, and evolving attitudes across different pandemic waves. Furthermore, studies like Savulescu et al. suggest that declining disease severity and the relatively short-lived protection of boosters may have influenced HCWs’ vaccine confidence. Incorporating this perspective into the discussion will strengthen your argument.

Thank you

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

Reviewer #4: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

Reviewer #4: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

Reviewer #4: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

Reviewer #4: No

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Reviewer #3: Dear Colleagues, thank you for your significant effort to collect and analyse such amount of data.

Several studies addressing vaccine hesitancy or acceptance in lay-people are documenting a more complex picture than just fear/extreme fear. A recent paper [Dumitra GG et al - Segmenting attitudes toward vaccination – behavioural insights into influenza vaccination refusal in Romania. GERMS. 2024;14(4):362-374. doi: 10.18683/germs.2024.1446] documented 3 distinct latent-class groups of people regarding vaccine and disease perception. Highest refusal was present in people that perceived lack of necessity and belief in natural immunity. A smaller degree of refusal was documented in people with past negative experiences with vaccines or distrust in vaccines.

Can you comment about these findings compared with your statement in page 25 "personal history of COVID-19 infection, and experiencing side effects of COVID vaccination were associated with lower vaccine confidence" after stating in page 24 "Research investigating vaccine confidence in HCWs with a previous history of COVID-19 infection also yields mixed results, with some studies reporting high confidence [75], while others suggest low confidence [76]. It is worth emphasizing that the firsthand experience of the disease's severity and its impact play a crucial role in shaping confidence toward vaccination"

These seem to document different perception models from HCW in your study and general population, probably because of major differences in disease perception [did you ask in your study if responding HCW were working in a unit where COVID-19 patients were isolated/treated?].

Experiencing first-hand disease severity decrease during different waves of pandemic (after Delta wave all subsequent Omicron lineages were less and less devastating), several groups of HCW decreased in fear and potentially developed a more relaxed behaviour and less adoption of recurrent boosters. Some sense of "futility" of boosting was inflicted by a certain perception bias, when confronted with the relative short period of protection gained by boosting as documented in an European study performed in 10 countries and 19 hospitals (Savulescu C, et al. Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021–May 2023. Vaccines. 2024; 12(11):1295. https://doi.org/10.3390/vaccines12111295).

Reviewer #4: Dear Authors,

I want to congratulate you on the topic of your article, given the crucial importance of vaccination among healthcare professionals from a preventive perspective. Understanding the psychosocial factors influencing COVID-19 vaccination is essential—not only for protecting healthcare workers themselves but also for their patients, as they play a direct role in their immunization efforts.

However, I believe the manuscript requires some revisions before it can be considered for publication. Below, I outline the necessary changes and provide several questions that I would like to see addressed:

1. Title: Please revise to include the phrase “…amid Emerging Variants”.

2. Introduction: The section is too long and needs to be restructured. It includes a significant amount of information that is not directly relevant to the study. Additionally, there is a lack of coherence between successive paragraphs, which seem to have been written independently. The introduction should have a clear and logical flow, which is currently missing. Please revise.

3. Sample Selection Bias: The study relies on a convenience sample, including only healthcare professionals with internet access. Could this introduce a significant selection bias, particularly in countries where internet access may be limited? How was this issue addressed? Was any measure taken to mitigate its impact?

4. Data Collection Tools section: This section should be more concise, with detailed information on survey questions moved to an appendix. Additionally, since previously validated scales were used, their descriptions should be minimized, referring readers to the original publications for further details.

5. Language of the Questionnaire: was the questionnaire administered in English in all countries? If so, could this be a limitation for participants in certain regions?

6. Results Section: Given the large number of tables and figures, I suggest moving the initial tables on sociodemographic characteristics to a supplementary file. Moreover, the narrative description is overly detailed, often repeating information already provided in the tables. Please revise.

7. Sample Representativeness: While the study appears methodologically well performed, I have concerns about the representativeness of the sample. First, the rationale for grouping these specific countries together is unclear. Second, to what extent do the selected healthcare professionals represent the broader population of healthcare workers in each country? Was any assessment of representativeness conducted? For example, does the sample reflect national distributions in terms of gender, age group, and occupation?

8. Multivariate Analysis: The analysis does not appear to adjust for country. Given the diversity of the countries studied, do you not consider this a potential confounding factor? Beliefs and attitudes toward vaccination are likely influenced by the socioeconomic and cultural contexts of each country, making it essential to account for these differences in the analysis. Please consider this suggestion.

9. Discussion Section: The discussion lacks structure and is difficult to follow. Given its length, I recommend restructuring it into subsections to improve readability and comprehension.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #3: Yes:  Mihai Craiu

Reviewer #4: No

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Dear Dr. Ghazy,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Thank you for your submission addressing a timely and important topic. The focus on vaccine hesitancy during the pandemic is highly relevant, and your efforts to capture cross-national perspectives are commendable. However, to improve the scientific rigor and clarity of the manuscript, several key areas require attention. Please ensure that all figures are correctly embedded in the manuscript and that abbreviations such as "VH" are clearly defined upon first use. Additionally, clarify ambiguous response categories (e.g., "others" in place of residence) to enhance interpretability. The Results section could be more concise by removing redundant tables (e.g., Tables 1 and 2), as the content is already described in the narrative. It would also be helpful to specify the type of vaccine (e.g., monovalent or bivalent) referenced, to align with evolving public health contexts. While the cross-sectional design limits causal inference, your findings still offer valuable insights and may serve as a useful foundation for future research and policy discussions. I encourage you to revise the manuscript accordingly to improve its clarity, coherence, and contribution to the field.

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Please submit your revised manuscript by Aug 24 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

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Mona Gamal Mohamed

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The aim of this research is timely and relevant, particularly in the context of ongoing global discussions surrounding vaccine hesitancy and the evolving dynamics of the COVID-19 pandemic. While the cross-sectional design and use of a simple questionnaire limit the depth of scientific inquiry, the inclusion of participants from multiple countries adds value by offering broad, generalized insights that could inform future research and public health policy. However, several critical revisions are necessary to strengthen the manuscript. First, clarify abbreviations such as "VH" upon first use and specify what is included under "others" in the place of residence category. Please also ensure that all figures are correctly displayed and embedded in the manuscript. Consider whether it would be beneficial to indicate the version of the vaccine (monovalent or bivalent) to align with variant-specific developments. To improve the clarity and conciseness of the Results section, we recommend removing Tables 1 and 2, as their content is already described in the text, and consider including Supplementary Table 2, which appears to be missing. Addressing these points will enhance the manuscript’s overall clarity, relevance, and impact for a broad audience.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

Reviewer #5: (No Response)

Reviewer #6: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

Reviewer #5: Yes

Reviewer #6: Partly

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3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

Reviewer #5: N/A

Reviewer #6: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

Reviewer #5: Yes

Reviewer #6: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

Reviewer #5: Yes

Reviewer #6: No

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Reviewer #3: Dear colleagues, thank you for the persistent effort made in improvement of your research especially in the Discussion section that was significantly improved by inserting clarifications in sections like "Fear of Emerging COVID-19 Variants Among HCWs", "Confidence in the received COVID-19 Vaccines" or "Interplay between fear of new SARS-Cov-2 variant infection and confidence in the received vaccine". Also valuable improvement has been implemented in Study Limitations section. Congratulations for your detailed revision of this paper.

Reviewer #5: Thanks to all authors for their competitive work, please find some comments below:

1- Introduction: A study on 2,336 HWCs reported an increasing rate of severe COVID-19 fear from 9% to 15% please give details how you concluded its increase, is it a longitudinal study?

2- Methods: You mentioned (A nationwide); however, this study has a global outreach, what nation did you mean?

3- Regarding age distribution, 86 was the maximum, this age for healthcare worker is a bit weird.

4- In conclusion, HCWs exhibited notable fear of SARS-CoV-2 new variants with low confidence. Better to add infection to be notable fear of infection with SARS-CoV-2 new variants with low confidence

5- Sample size calculation: We multiplied by 4 to compensate for stratification (Western region, Arab region, African region, and Others). I would advise you to add the total sample size

6- Kindly note that WHO classifies variants as variants of concern, variants of interest and variants under monitoring. CDC classifies variants as variants of concern, variants of interest, and variants of high consequence. Nomenclature by WHO is a bit more recent.

7- Do you add the version of vaccine Monovalent / bivalent to coincide with the updated form of variants?

8- Please clarify what is VH in the first time its mentioned in the text.

9- Please take care that figures are not displayed in the manuscript provided to me for review, you must ensure their inclusion.

10- Place of residence included others, please define what are the others?

11- Discussion: Key brain regions, such as the amygdala, insula, and prefrontal cortex, play important roles in processing fear, risk perception, and decision making. What does this statement add to the discussion?

Reviewer #6: The aim of this research is pertinent topic for examination at this phase of pandemic and with the common concerns about the pharmaceutical intervention. The cross-sectional study design, with broad questions in simple questionnaire survey, mean that depth is lacking for true scientific inquiry (thus, "partly" for Review Question #2), but the inclusion of multiple countries mean that these generalized findings may help understanding for non-specific audience of readers. The claims could be useful, even if refuted by more rigorous design, for further medical research and informing public health policy.

With these strengths, there are some suggestions (in response to Question #1) made by previous reviewers which could vastly improve the study manuscript. I agree that the Results sections has too many tables with the same information are already written in the text. My suggestion is to delete Tables 1 and 2 to reduce the size of this section and possibly include the Supplementary Table #2 (unavailable in the current manuscript).

Major omissions in document will require fix for the final submission (in response to Question #4): Figure 1 & 2 are missing from Pages 24 & 27 in the version I received; and there is no "Supplementary Table 2" available. I was unable to review these inserts of results.

As noted in previous reviews and still not resolved satisfyingly, the wording in the manuscript is imprecise and also the flow of introduction & discussion are too general and off-topic ("no" on Question #5) seemingly like an early draft. I have some specific improvements here:

Page 1: Short title: Misspelling "SARS-Cov2"

Page 1: Abstract conclusion: Revise to "In conclusion, HCWs exhibited notable fear of emerging SARS-CoV2 variants and there is low level of confidence in COVID-19 vaccination"

Page 16: In stead of "vaccine effectiveness concerns surfaced", there were new questions about "duration of protection" and "effectiveness against new variants" questions post-Omicron variant emergence

"SARS-Cov-2 vaccine approval" should be written "COVID-19 vaccine approval,".. Moreover, there are concerns over "how immunity from vaccines might influence viral evolution of spike protein"

Page 18: Use "of either sex" because you can't have a study participant who is both sexes at once

Page 23: Hypertension is chronic "condition" not disease. Use "the most reported health problems"

Page 28: Table 5 Row title use "Area of practice in healthcare work" deleting Field of study to support statement in discussion on Page 32 "Working as a physician, dentist, pharmacist, or physiotherapist was associated with

lower levels of fear."

Page 31 "Neural substrates" is off topic and should be removed. Focus discussion on study related measurements, like which HCW had increased fear, or Discussion documented number of deaths in surveyed countries correlate with fear?

Again, a general discussion about marital happiness is out of focus on COVID-19 fear. What about illness support through marriage

Page 32 Discussion missed a large issue of interest, on if Confidence is related according to vaccine received?

Page 34 What about high non-response rate? Is the missing population a limitation in your findings?

Page 34 Length of time (2 years +) since vaccines introduced should be discussed as aspect of study finding on confidence of vaccine (as well as fear of new variants); Furthermore, have better treatments become available during the time since pandemic to ease fears of death and severe illness from new COvID-19 infection

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #3: Yes:  Mihai Craiu

Reviewer #5: No

Reviewer #6: Yes:  C. Jason McKnight

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

Cross-National disparities in healthcare workers' perceptions: examining fear of infection and confidence in the received COVID-19 vaccines amid emerging variants

PONE-D-24-28390R5

Dear Dr. Ramy

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Eman Abdelaziz Rashad Dabou, Ph.D, M.S.N

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

After reviewing the peer reviewers’ comments and noting that all concerns satisfactorily addressed, I accept the manuscript.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

Reviewer #5: All comments have been addressed

Reviewer #6: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #3: Yes

Reviewer #5: Yes

Reviewer #6: Yes

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3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #3: Yes

Reviewer #5: I Don't Know

Reviewer #6: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #3: Yes

Reviewer #5: Yes

Reviewer #6: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #3: Yes

Reviewer #5: Yes

Reviewer #6: Yes

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Reviewer #3: Dear colleagues in page 33 of your revised version you are stating that tailoring approach is paramount: "These findings underscore the need for providing targeted educational programs and personalized psychological support and encourage open communication to address these concerns effectively and to dispel uncertainties, particularly regarding efficacy and side effects."

Do you think that new AI tools that can be used to screen across Social Media posts could be used to target such perception threats that can be approached in a timely manner, in a similar strategy like one used in commercial trends analysis that is used to boost managing options and sales?

Big data mining processes could uncover some perception threats or bottlenecks in adopting proactive preventive measures like immunizations in a much faster rhythm compared to conventional cross-sectional studies delivered by various platforms, like current study.

Vaccine hesitancy will probably increase globally because of polarization of communication and because of recent official statements of extremely important public figures. So, we will need a more accurate and rapid pathway of exploring VH future trends, not only simple cross-sectional approaches, and newly developing AI tools could be implemented in the foreseeable research.

Reviewer #5: Thanks a lot, dear authors for addressing my comments.

I have final suggestion that might enhance the presentation of your results.

Can you please use the same nomenclature to classify the regions of data collection to WHO regions include the African Region (AFRO), the Eastern Mediterranean Region (EMRO), the South-East Asia Region (SEARO), the Region of the Americas (AMRO), the Western Pacific Region (WPRO), and the European Region (EURO)

Reviewer #6: Overall: Accept. The author has revised the manuscript and made substantial changes based on the reviewer feedback. The document is now acceptable for publication.

Remaining Correction:

Page 13 of Results (23 of Document: “Approximately 30%” or “Exactly 30.4%” not Exact to start sentence

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #3: Yes:  Mihai Craiu MD PhD

Reviewer #5: No

Reviewer #6: Yes:  C. Jason McKnight

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Attachments

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Submitted filename: Comments COVID19 FEAR - REVIEWER5.doc