Effectiveness of the Pfizer-BioNTech (BNT162b2) vaccine against the omicron variant of SARS-CoV-2 among adults aged 50 and above: A case-control study in Lebanon, June 2022

Maryo Baakliny; Nada Ghosn; Nadine Saleh; Patrick Maison

doi:10.1371/journal.pone.0318344

Peer Review History

Original SubmissionMay 20, 2024
20 May 2024 Author Response https://doi.org/10.1371/journal.pone.0318344.r001
16 Sep 2024 Decision Letter - Marwan Osman, Editor PONE-D-24-09717Effectiveness of the Pfizer-BioNTech Vaccine against the Omicron Variant of SARS-CoV-2 among Adults Aged 50 and Above: A Case-Control Study in Lebanon, June 2022PLOS ONE Dear Dr. Baakliny, 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 Oct 31 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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[Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: No ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Comments to the author Thank you for the opportunity to review the manuscript “Effectiveness of the Pfizer-BioNTech Vaccine against the Omicron Variant of SARSCoV-2 among Adults Aged 50 and Above: A Case-Control Study in Lebanon, June 2022”. The study assessed vaccine effectiveness and adjusted the model based on confounders, providing a nuanced understanding of vaccine effectiveness in real-world settings. This methodology can be adopted for various vaccines in future pandemics. The manuscript is technically sound and supports its conclusions effectively. The statistical analysis is performed rigorously, with appropriate methods and sample sizes ensuring reliable results. The manuscript is presented clearly and written in standard English, making it easily understandable. The data presented is well-aligned with the conclusions drawn. Overall, the study is well-executed and adheres to the required standards of clarity and scientific rigor. However, minor revisions are needed to improve the clarity and structure of the article. Comment 1: In the abstract, there are redundant ideas present in these two paragraphs. It is preferable to consolidate this idea into a single, clear statement to avoid duplication. “Factors such as age, province of residence, and underlying conditions significantly influenced VE. The study underscores the need for on-going monitoring and potential booster doses to enhance protection, especially against evolving variants like Omicron.” “Factors such as age, province of residence, and underlying conditions exert significant influence on VE, highlighting the need for tailored vaccination strategies. Booster doses may play a crucial role in enhancing VE and mitigating the impact of evolving strains like Omicron.” Comment 2: There seems to be an error in the percentage calculations in the following paragraph in the introduction section. Please review and update the percentages accordingly. “Whereas in Lebanon as of 17 February 2022 5,779,829 vaccine administered in total (7). The Pfizer, BioNTech vaccine was the most administered with 4,253,218 doses (82,9%) followed by AstraZeneca 717,304 (13.9%); added together they make 96.8 % of the brands administered.” Comment 3: “Introduction: This study aims to highlight the effectiveness of the Pfizer-BioNTech vaccine brand against the Omicron variant of SARS-CoV-2, focusing on individuals aged 50 and above presenting with influenza-like illness at sentinel sites.” Could you please explain why you chose to study this specific population? If there is a particular reason, it would be more informative to include this rationale in the methodology section of the article. Comment 4: Please include relevant dates in the methodology section, specifically the periods of patient recruitment. Comment 5: The methodology is clear and well written. However, I recommend creating a specific section for data analysis instead of merging it with study design or data collection sections. For example: “The outcome of interest for the primary analysis will be the detection of SARS-CoV-2 in patients eligible for vaccination and presented to ILI/CLI sites with symptoms fitting the case definition.” This information was stated in the study design section. However, this should be mentioned in the data analysis section. “Data analysis was done using R version 4.0.2 and R Studio. The measure of association is an odds ratio (OR). This can be measured by logistic regression taking into considerations all the confounding factors cited in the literature.” This information was stated in the data collection section. However, this should be mentioned in the data analysis section. In addition, it would be beneficial to provide more details on how quantitative variables were handled in the analyses and describe all statistical methods used. Comment 6: How were the confounders chosen? Did you base your selection solely on the literature, or did you also consider the results of the bivariate analysis? Comment 7: The result section is well-structured. However, there is a replication of results between the text and the tables; for example, the disease manifestations paragraph repeats all the results of table 2. To avoid duplication, it is recommended to report only the most prevalent manifestations or the significant results in the text. The remaining variables can be presented in the table. Comment 8: In the result section, specifically the “Table 2: Logistic regression adjusted to confounders with OR”, it is recommended to add the confidence interval and p-value of the OR. In addition, in this same table, it would be beneficial to add the results of the confounding variables considered in the logistic regression model, and not to present only the vaccination status variable. (you can present at least the variables with significant results). Comment 9: In the discussion section, you mentioned that: “An OR less than one were seen for the fever, headache, nausea, myalgia, vomiting, loss of taste, loss of smell this is seen when the vaccination plays a protective effect against one of the symptoms.” However, according to the table 3, the P-value for “headache” is 0.212, which is a not statistically significant. This needs to be adjusted in the text. Comment 10: The conclusion section is well-written, summarizing the main results and outlining the implications for future research. However, I suggested moving the first paragraph of the conclusion (“Knowing that we have limited facts --> for the Gamma variant during the same time frame (17)”) to the discussion section. This paragraph compares the study results with other studies conducted in the UK and South Africa, making it more appropriate for the discussion section. Comment 11: Please review the numbering of the tables. Reviewer #2: The study titled “Effectiveness of the Pfizer-BioNTech Vaccine against the Omicron Variant of SARS-CoV-2 among Adults Aged 50 and Above: A Case-Control Study in Lebanon, June 2022” focuses on an important topic however various issues are associated with the manuscript. The below recommendations should be paid attention to in order to ensure proper presentation of the paper and utilization/interpretation of results. -Please ensure to state what acronym stand for when the acronym is used for the first time (eg. SARI in study design instead of study population). -Also please keep consistent towards the terminologies used and avoid typos (SARS-CoV-2 vs SARSCoV-2 in study design section). -Ethical consideration section should have been in past tense (why were “will” and “should” included in this part?) - The manuscript needs to go through an overhaul in terms of organization. It is unclear what the table containing the chronic diseases right underneath table 1 is? Also, table formats should be consistent. - Please keep spacing and spacing before/after punctuation consistent. - The manuscript should be read very carefully to correct typos and grammatical issues. Many typos and punctuation errors exist. - A more elaborate discussion / conclusion is required to ensure that results are thoroughly discussed and elaborated on. -The authors should check to see if there is any correlation between the timing of vaccination and the symptoms observed. For instance, previous work (Barin et al., Lancet Microbe, 2022 and others) demonstrated a significant reduction in antibody titers over time so it is crucial to observe if the symptom severity is reduced in recently vaccinated individuals. Please carry out correlation studies in the light of different vaccination times and symptoms experienced. -Why weren’t the results for thyroid disorders, neurological disorders, autoimmune Diseases included in the report? This could provide interesting and novel information. ****** 6. PLOS authors have the option to publish the peer review history of their article (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 #1: No Reviewer #2: No ******** [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 . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0318344.r002
Revision 1
6 Nov 2024 Author Response We sincerely appreciate the reviewers' thoughtful feedback and have made revisions accordingly to enhance the clarity and depth of our manuscript. Below is a detailed table that outlines each of the reviewers' comments, along with our corresponding responses and the actions taken to address them. Response to Reviewer One: Thank you for your constructive feedback, which helped improve the clarity and quality of our manuscript. Comment 1: In the abstract, there are redundant ideas present in these two paragraphs. It is preferable to consolidate this idea into a single, clear statement to avoid duplication. “Factors such as age, province of residence, and underlying conditions significantly influenced VE. The study underscores the need for on-going monitoring and potential booster doses to enhance protection, especially against evolving variants like Omicron.” “Factors such as age, province of residence, and underlying conditions exert significant influence on VE, highlighting the need for tailored vaccination strategies. Booster doses may play a crucial role in enhancing VE and mitigating the impact of evolving strains like Omicron.” We agree that the two paragraphs in the abstract contained redundant ideas. We have revised and consolidated them into a single, clearer statement as follows: Factors such as age, province of residence, and underlying conditions significantly influenced VE. The study underscores the need for an on-going monitoring and potential booster doses to enhance protection, especially against evolving variants like Omicron and emphasizes the importance of proactive measures in safeguarding public health amidst evolving viral threats. Comment 2: There seems to be an error in the percentage calculations in the following paragraph in the introduction section. Please review and update the percentages accordingly. “Whereas in Lebanon as of 17 February 2022 5,779,829 vaccine administered in total (7). The Pfizer, BioNTech vaccine was the most administered with 4,253,218 doses (82,9%) followed by AstraZeneca 717,304 (13.9%); added together they make 96.8 % of the brands administered.” We have reviewed the numbers and corrected the percentages accordingly. The revised paragraph now reads: Whereas in Lebanon as of 17 February 2022 5,779,829 vaccine had been administered in total by the same time[7] .The Pfizer, BioNTech vaccine was the most administered with 4,253,218 doses (73.58 %) followed by AstraZeneca 717,304 (12.41%); added together they make 85.9% of the total brands administered. Comment 3: “Introduction: This study aims to highlight the effectiveness of the Pfizer-BioNTech vaccine brand against the Omicron variant of SARS-CoV-2, focusing on individuals aged 50 and above presenting with influenza-like illness at sentinel sites.” Could you please explain why you chose to study this specific population? If there is a particular reason, it would be more informative to include this rationale in the methodology section of the article. We chose to focus on individuals aged 50 and above in this study because in Lebanon, the Pfizer-BioNTech vaccine was primarily administered to healthcare workers and individuals in this age group due to their higher risk of severe outcomes from COVID-19. Clarification was added in the methodology section. Comment 4: Please include relevant dates in the methodology section, specifically the periods of patient recruitment. We have updated the methodology section to include the relevant dates for patient recruitment. The revised sentence now reads: Data collection was conducted from February till the end of April. Comment 5: The methodology is clear and well written. However, I recommend creating a specific section for data analysis instead of merging it with study design or data collection sections. For example: “The outcome of interest for the primary analysis will be the detection of SARS-CoV-2 in patients eligible for vaccination and presented to ILI/CLI sites with symptoms fitting the case definition.” This information was stated in the study design section. However, this should be mentioned in the data analysis section. “Data analysis was done using R version 4.0.2 and R Studio. The measure of association is an odds ratio (OR). This can be measured by logistic regression taking into considerations all the confounding factors cited in the literature.” This information was stated in the data collection section. However, this should be mentioned in the data analysis section. In addition, it would be beneficial to provide more details on how quantitative variables were handled in the analyses and describe all statistical methods used. A new section was added as suggested : Data analysis: The outcome of interest for the primary analysis was the detection of SARS-CoV-2 in patients eligible for vaccination and presented to ILI/CLI sites with symptoms fitting the case definition. Data analysis was done using R version 4.0.2 and R Studio. Descriptive statistics were calculated to summarize the demographic and clinical characteristics of the participants, frequencies and numbers were reported for categorical variables and comparisons of percentages between groups were made using Pearson's Chi-square tests for categorical variables to assess the significance of observed differences. The measure of association was the odds ratio (OR). This was can be measured by the logistic regression taking into considerations all the confounding factors cited in the literature. Comment 6: How were the confounders chosen? Did you base your selection solely on the literature, or did you also consider the results of the bivariate analysis? Explanation was added to the methods section: The selection of confounders was based on the guideline by WHO for VE studies. Following this, we performed bivariate analyses to explore associations between these factors and the outcome of interest and all variables with p value less than 0.2 were added. This dual approach allowed us to ensure that our confounder selection was comprehensive and grounded in both theoretical and empirical evidence. The chosen confounders included age groups, gender, province of residence, smoking status, underlying conditions, coverage of basic needs, recent contact with a COVID-19 case, exposure to public transportation, social events, travel, mask use, social distancing, handwashing, hand sanitizer use, and nationality. Comment 7: The result section is well-structured. However, there is a replication of results between the text and the tables; for example, the disease manifestations paragraph repeats all the results of table 2. To avoid duplication, it is recommended to report only the most prevalent manifestations or the significant results in the text. The remaining variables can be presented in the table. To enhance clarity and reduce redundancy, we revised the results section and adjusted accordingly. Comment 8: In the result section, specifically the “Table 2: Logistic regression adjusted to confounders with OR”, it is recommended to add the confidence interval and p-value of the OR. In addition, in this same table, it would be beneficial to add the results of the confounding variables considered in the logistic regression model, and not to present only the vaccination status variable. (you can present at least the variables with significant results). We have revised “Table 2” and adjusted the title to “table 8”: Logistic regression adjusted to confounders with OR” to include the confidence intervals (CIs) and p-values for the odds ratios (OR), as requested. Additionally, we have expanded the table to include the results for the confounding variables considered in the logistic regression model. Comment 9: In the discussion section, you mentioned that: “An OR less than one were seen for the fever, headache, nausea, myalgia, vomiting, loss of taste, loss of smell this is seen when the vaccination plays a protective effect against one of the symptoms.” However, according to the table 3, the P-value for “headache” is 0.212, which is a not statistically significant. This needs to be adjusted in the text. Adjusted upon your comment to be: However, while the OR for headache and dyspnea was also less than one, this result was not statistically significant. Comment 10: The conclusion section is well-written, summarizing the main results and outlining the implications for future research. However, I suggested moving the first paragraph of the conclusion (“Knowing that we have limited facts --> for the Gamma variant during the same time frame (17)”) to the discussion section. This paragraph compares the study results with other studies conducted in the UK and South Africa, making it more appropriate for the discussion section. We agree that the first paragraph of the conclusion, which compares the study results with other studies conducted in the UK and South Africa, is more suited to the discussion section. We have now moved the paragraph to the discussion section. Comment 11: Please review the numbering of the tables. Reviewed and adjusted. Response to Reviewer Two: thank you for your detailed review and insightful suggestions. Your input has significantly contributed to refining our work. Comment 1: Please ensure to state what acronym stand for when the acronym is used for the first time (eg. SARI in study design instead of study population). It was adjusted accordingly and we have also reviewed the document to confirm that other acronyms are similarly defined upon their first use to enhance clarity for readers. Comment 2: Also please keep consistent towards the terminologies used and avoid typos (SARS-CoV-2 vs SARSCoV-2 in study design section). We have carefully reviewed the manuscript to ensure that the terminology is consistent throughout the document. Comment 3: Ethical consideration section should have been in past tense (why were “will” and “should” included in this part?) We have revised the section accordingly. Comment 4: The manuscript needs to go through an overhaul in terms of organization. It is unclear what the table containing the chronic diseases right underneath table 1 is? Also, table formats should be consistent. Thank you for your feedback. We recognize the importance of a clear and consistent structure throughout the manuscript. The table containing chronic diseases beneath Table 1 was unintentionally misplaced and was relocated to the appropriate section for clarity. Additionally, we ensured that all table formats are consistent. Comment 5: Please keep spacing and spacing before/after punctuation consistent. Thank you for highlighting this. We have thoroughly reviewed the entire manuscript to ensure consistency in spacing. Comment 6: The manuscript should be read very carefully to correct typos and grammatical issues. Many typos and punctuation errors exist. The manuscript has undergone a comprehensive review to address and correct all typos, grammatical issues, and punctuation errors. Comment 7: A more elaborate discussion / conclusion is required to ensure that results are thoroughly discussed and elaborated on. We have expanded both the discussion and conclusion sections to provide a more comprehensive analysis of our results. Comment 8: The authors should check to see if there is any correlation between the timing of vaccination and the symptoms observed. For instance, previous work (Barin et al., Lancet Microbe, 2022 and others) demonstrated a significant reduction in antibody titers over time so it is crucial to observe if the symptom severity is reduced in recently vaccinated individuals. Please carry out correlation studies in the light of different vaccination times and symptoms experienced. Thank you for your valuable suggestion regarding the correlation between the timing of vaccination and the symptoms observed. However, due to the constraints of our current dataset, we were unable to perform a thorough correlation analysis between vaccination timing and the symptoms experienced by participants. We emphasized this limitation in the revised manuscript and suggest it as a direction for future studies. Comment 9: Why weren’t the results for thyroid disorders, neurological disorders and autoimmune diseases included in the report? This could provide interesting and novel information. The primary reason these results were not included in the report is due to limitations in our sample size and the statistical power needed to analyze these specific disorders. During the analysis, we found that the prevalence of these conditions within our study population was low and were cited as others in free text, which limited the ability to draw meaningful conclusions or to perform robust statistical analyses. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0318344.r003
17 Dec 2024 Decision Letter - Marwan Osman, Editor PONE-D-24-09717R1Effectiveness of the Pfizer-BioNTech Vaccine against the Omicron Variant of SARS-CoV-2 among Adults Aged 50 and Above: A Case-Control Study in Lebanon, June 2022PLOS ONE Dear Dr. Baakliny, 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 31 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. Please include the following items when submitting your revised manuscript: 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, Marwan Osman, PhD, MPH 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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #3: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #3: I Don't Know ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: All the comments have been addressed by the author which make the manuscript more organized and clearer. No additional comments are requested. Reviewer #3: My previous comments have been sufficiently addressed. Some things to add would be to state which version of Pfizer Biontech vaccine was implemented and considered during study time as many different updated vaccines emerged. Some of those were more effective against omicron than others. Similarly, please clarify what is meant by “fully vaccinated” in the “Definition of vaccination status:” section highlighting which vaccine version was considered. The originally implemented ones? If so please clarify accordingly. I agree with the statement in the discussion which states “ Key findings of the study indicate that the Pfizer-BioNTech vaccine is effective in reducing the odds of developing symptomatic COVID-19.” This should have been highlighted more and emphasized in the abstract as it is an important finding. The abstract reads almost as vaccination not having an enough positive impact where the authors' key findings clearly indicates otherwise. Please update accordingly. ****** 7. PLOS authors have the option to publish the peer review history of their article (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 #1: No Reviewer #3: No ******** [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 . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0318344.r004
Revision 2
7 Jan 2025 Author Response Greetings, Response to Reviewers: Thank you for your valuable feedback which has helped enhancing the clarity and precision of our study and for acknowledging that the previous comments have been addressed sufficiently. Review comment to the Author: Reviewer #3: My previous comments have been sufficiently addressed. Some things to add would be to state which version of Pfizer Biontech vaccine was implemented and considered during study time as many different updated vaccines emerged. Some of those were more effective against omicron than others. Similarly, please clarify what is meant by “fully vaccinated” in the “Definition of vaccination status:” section highlighting which vaccine version was considered. The originally implemented ones? If so please clarify accordingly. I agree with the statement in the discussion which states: Key findings of the study indicate that the Pfizer-BioNTech vaccine is effective in reducing the odds of developing symptomatic COVID-19. This should have been highlighted more and emphasized in the abstract as it is an important finding. The abstract reads almost as vaccination not having an enough positive impact where the authors' key findings clearly indicates otherwise. Please update accordingly. Response to reviewer #3: Response to Reviewer #3 Regarding your additional suggestions: 1. Pfizer-BioNTech Vaccine Version: We appreciate your suggestion to specify the version of the Pfizer-BioNTech vaccine implemented during the study. During the study period, the original Pfizer-BioNTech COVID-19 vaccine (BNT162b2) was the version available and administered in Lebanon. We have updated the manuscript to clarify this point. 2. Definition of “Fully Vaccinated”: We have clarified the definition of “fully vaccinated” in the “Definition of vaccination status” section. In the context of this study, “fully vaccinated” refers to individuals who received the complete initial series of the original Pfizer-BioNTech COVID-19 vaccine (two doses of BNT162b2). This definition has been adjusted in the manuscript to avoid any ambiguity. 3. Abstract adjustments: We have revised the abstract to state the protective effects of vaccination, including its role in mitigating symptom severity. Thank you again for your thoughtful remarks. Dear editors, Thank you for your feedback. We have reviewed the reference list and made the necessary updates and adjustments as per your recommendations. The following changes have been made: 1. Reference 2: The link to the Centers for Disease Control and Prevention (CDC) website has been updated as follows: o Centers for Disease Control and Prevention. (n.d.). Ncov 2019 – Variants classifications. Available from: https://www.cdc.gov/covid/?CDC_AAref_Val=https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html (visited 20-9-2022). 2. References 5 and 13: Typographical errors were corrected as follows: o Tan, S. H., Cook, A. R., Heng, D., Ong, B., Lye, D. C., Tan, K. B., et al. (2022). Effectiveness of BNT162b2 vaccine against Omicron in children 5 to 11 years of age. New England Journal of Medicine, 387(6), 525–532. https://doi.org/10.1056/NEJMoa2203209. o Li, Q. H., Ma, Y. H., Wang, N., Hu, Y., & Liu, Z. Z. (2020). New coronavirus-infected pneumonia Engulfs Wuhan. Asian Toxicology Research, 1, 1–7. Best Regards, Attachments Attachment Submitted filename: Response to Reviewers 1.docx https://doi.org/10.1371/journal.pone.0318344.r005
15 Jan 2025 Decision Letter - Marwan Osman, Editor Effectiveness of the Pfizer-BioNTech Vaccine against the Omicron Variant of SARS-CoV-2 among Adults Aged 50 and Above: A Case-Control Study in Lebanon, June 2022 PONE-D-24-09717R2 Dear Dr. Baakliny, 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Marwan Osman, PhD, MPH Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0318344.r006
Formally Accepted
Acceptance Letter - Marwan Osman, Editor PONE-D-24-09717R2 PLOS ONE Dear Dr. Baakliny, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Marwan Osman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0318344.r007

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