PONE-D-22-03333COVID-19 population-based survey in Maricá, Brazil: the impact of vaccination in viral incidence.PLOS ONE

Dear Dr. Tanuri,

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 by both reviewers.

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Odir Antonio Dellagostin

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?

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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: No

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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5. Review Comments to the Author

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Reviewer #1: The manuscript “COVID-19 population-based survey in Maricá, Brazil: the impact of vaccination in viral incidence” submitted to PlosOne Journal presented data about the decrease in the incidence of COVID-19 according to the level of vaccination in a Brazilian city, investigating data of three repeated cross-sectional from 1134 subjects in a population-based epidemiological study from May to August 2021.

It is an interesting study. However, I would like to discuss some aspects with the authors to improve the manuscript before publication. I recommend the authors revise the results description and indications of the figures and tables in the text. Also, a revision of the conclusion. In summary, the study can be published after minor revision. Questions, comments, and suggestions are listed below:

Major comments:

#1 Introduction: Since it is currently well known that vaccination prevents COVID-19 infection, I recommend including the reasons to explore this issue in this article. Some points:

For example, in comparison or sequence with other studies, what novelty this relevant study may corroborate? Is it because of the Brazilian context during the period? Is it because of the specific behavior of the population in this local? Was it not expected that the vaccine promotes an increase of neutralizing antibody levels, or during this period, this was unknown information? The type of vaccine applied vs. variant prevalence can be included as a novel aspect for readers?

To summarize, it is not clear the novelty end contribution of the study for readers in the introduction section. The authors presented clearly the study objective in the introduction: “our aim is to investigate SARS-CoV-2 antibody (anti-SCOV2) prevalence by city and RT-PCR results in a repeated cross-sectional study in a municipality”. However, the lack of information in the field that can be answered with the study is not completely clear in the introduction. For example, there are some comparisons made about vaccine type in the study. After reading the introduction section, this type of comparison is not expected for readers.

#2 Methods: The authors informed: “Subjects below 18 years old were excluded, and if the selected individual did not provide a sample, another household member was randomly selected.” During the period, teenagers had access to vaccination in this place? If they don’t, I suggest including this information as a reason not to include < 18 yo subjects. If they had access to the vaccine, please inform readers why not include them. All other information was adequately presented in methods such as ethical approval, population-based sampling procedures (areas and subjects), sample collection and analytical procedures (RT-PCR, serological tests…),

#3 Figure 1B showed an increase in the N1 target CT during the 2° transversal data collection cycle and a decrease in the next cycle. Is there some special meaning about this result according to the variant/period to be interpreted and discussed in the manuscript?

#4 The description of the results presented in figure 2 needs a revision. There is some repetition of information. Also, the text informed (line 292): “On the third cycle the anti-SCOV2 IgG positive rate decreased in vaccinated individuals with age above 60yo (Fig 2C)”. However, the decreasing is showed in the figure of unvaccinated individuals in the figure. (is it possible that groups were presented in the figure changed?). Also, the legend of figure 2 includes figures 2D, 2E, and 2F. However, these figures were not presented. In another hand, the results about the prevalence of NAB+ in unvaccinated vs. vaccinated subjects showed in the figure 2 were not described in the text.

#5 The discussion is adequately centered on the effect of vaccines on the reduction of COVID-19 impact. Also, there is a discussion about the type of vaccine. Because of these, I recommend above to include this expectation in the introduction for readers. Also, since the vaccine is not only the way to avoid the incidence of COVID-19, I recommend authors include a short paragraph in the discussion about the local recommendations and adherence of subjects in the period of the study in terms of social distancing and use of masks, for example. This is necessary to better understand of the context and also may help to improve the support of the conclusion: “The effect of vaccines”.

#6 Conclusion: I recommend deleting the text between lines 531-535, it is a description of the study again. Also, authors concluded an additional point not expected: “We also found a drop in the anti-SCOV2 IgG levels as well as NAb in individuals vaccinated CoronaVac more than 10 weeks supporting the use of an additional vaccine dose to boost the immune response in these individuals.” However, the study showed that Coronavac presented lower levels of protection in comparison with AstraZeneca and argued that these findings were due to the time after completing the vaccination scheme. For supporting this conclusion adequately, It was necessary to include results about the analysis of protection levels vs. time after vaccination in both vaccine regimens. However, the authors agree that this is not possible since “We could not see these drops in the AstraZeneca, Pfizer and Janssen vaccines due to a short period of time after immunization before our sampling”. Thus, since the decrease in the protection was not adequately presented in the study, this conclusion may not be adequate. I would like to hear the authors about it.

Minor points:

#7 Authors described the result of 26% of family history of COVID-19 as follows: “almost one-third of the 211 interviewed participants reported disease in relatives cohabiting the household.”. I suggest that the authors change this text for approximately one-fourth, not one-third.

#8 After the description of the results on lines 223-229, please indicate for readers to find these results in table S1;

#9 Is the text described in lines 348-351 about the results presented in figure 3? The comparison about IGG levels using only COVID positive subjects could be presented with more details, in the text of including a graph in figure 3.

Reviewer #2: The study evaluates the seropositive gains CPVO-19 according with vaccinal status, over time in Marica-RJ.

1. I suggest that the authors followed the STROBE statement Statement—Checklist of items that should be included in reports of cross-sectional studies.

2. The title must contain the study design.

3. The title specifies that the study evaluates the impact of the vaccination in viral incidence, but in the abstract the objectives was to evaluate the immunological status (antibodies against SARS-COV2), not the viral incidence (see title, pg 57 and pg 105-107). Please adapt the title.

4. The conclusion of the abstract refers to drop in mortality, that was not supported in the data presented. There is no mortality data in the study.

5. In the methods section, the sampling process description should include the period of recruitment and also explain how the study size was arrived at. The eligibility criteria and exclusion must be described. How the study handled with illiterate participants or individual with special needs?

6. The main outcomes need to be clearly defined, as well as exposures, predictors, potential confounders, and effect modifiers.

7. The data analysis must contain the test used do calculate effectiveness and also include how the immunological variables were handled. Additionally, must contain the software used for data analysis.

8. Regarding the results, please confirm that the number of participants with previous COVID was the same (13) in all three cycles – Table 1.

9. Please include a measure of difference in the S1 table and Table 1 or add the measurements to the text. The paragraph 223-229 stated that there are differences between groups, but there is no statistical test associated to that.

10. In line 275 the authors stated that there is an increase in % of participants, but there is no statistical test associated. Please include a statistical test in Table 3.

11. The Figure 2 need a legend for the abbreviations - NAb+.

12. Please correct the figure 3 and add p-value for the differences between groups or add a legend to state what the number 1 1 1 1 means.

13. Please specify which figure/table the results from lines 348-351 refers to sentence 360-362. As well as for the correlation states in lines 371-372.

14. In Figure 5 is very confuse. The Y axis goes from 0-3 and the secondary axes from 0-100% without axis specification.

15. Inline 401, is not clear with outcome the effectiveness analysis refers to. Please clarify and add the statistical test.

16. The authors make different statements regarding the association of risk factors and the PCR positivity. These affirmation needs to be based on multivariate analysis to avoid confounding bias. Please add a multivariate analysis to evaluate the risk factors (Pgs 438-448) or modify the paragraph.

17. The authors should include a paragraph with the weaknesses of the study.

18. The incidence of COVID-19 could be not only because of vaccination status but also due to the probability of infection in a specific period of time, that depend also from community transmission rates and mitigation measurements. Please discuss this.

19. The manuscript needs a grammar English review.

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Reviewer #1: Yes: Thiago Gomes Heck

Reviewer #2: No

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PONE-D-22-03333R1COVID-19 cross-sectional study in Maricá, Brazil: the impact of vaccination coverage in viral incidencePLOS ONE

Dear Dr. Tanuri,

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, especially regarding the use of standard English.  Therefore, we invite you to submit a revised version of the manuscript after it has been checked for spelling, grammatical and punctuation errors. For exemple, in the abstract, the following sentences contain erros: "We made three cycles of study sampling a total of 59 1134 subjects during May to August 2021"; "...individuals carrying detectable IgG antibodies and neutralizing antibody (NAb) 61 levels was bigger in the vaccinated when compared to unvaccinated groups...". We recommend that the manuscript be revised by a native English speaker.

Please submit your revised manuscript by Jun 15 2022 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,

Odir Antonio Dellagostin

Academic Editor

PLOS ONE

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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:

[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.]

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COVID-19 cross-sectional study in Maricá, Brazil: the impact of vaccination coverage in viral incidence

PONE-D-22-03333R2

Dear Dr. Tanuri,

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.

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Kind regards,

Odir Antonio Dellagostin

Academic Editor

PLOS ONE

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