Prospective observational study and serosurvey of SARS-CoV-2 infection in asymptomatic healthcare workers at a Canadian tertiary care center

Victor H. Ferreira; Andrzej Chruscinski; Vathany Kulasingam; Trevor J. Pugh; Tamara Dus; Brad Wouters; Amit Oza; Matthew Ierullo; Terrance Ku; Beata Majchrzak-Kita; Sonika T. Humar; Ilona Bahinskaya; Natalia Pinzon; Jianhua Zhang; Lawrence E. Heisler; Paul M. Krzyzanowski; Bernard Lam; Ilinca M. Lungu; Dorin Manase; Krista M. Pace; Pouria Mashouri; Michael Brudno; Michael Garrels; Tony Mazzulli; Myron Cybulsky; Atul Humar; Deepali Kumar

doi:10.1371/journal.pone.0247258

Peer Review History

Original SubmissionNovember 2, 2020
12 Jan 2021 Decision Letter - Eric HY Lau, Editor PONE-D-20-34493 Prospective Observational Study of Screening Asymptomatic Healthcare Workers for SARS-CoV-2 at a Canadian Tertiary Care Center PLOS ONE Dear Dr. Ferreira, 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. The Authors are expected to address all the criticisms by all Reviewers. In particular, please clarify the study objectives and consider revising the title to fully reflect the study, define clearly symptoms compatible with COVID-19 (Reviewer #1), discuss study limitations and clarify selection of patients for serological test (Reviewer #2). In additional to the above comments, please address, Supp Table 2, please align the serological test results with the correct occupation. Please clarify if there were any nosocomial outbreaks in the University Health Network during the study period. Please submit your revised manuscript by Feb 25 2021 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Eric HY Lau, Ph.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data. Additional Editor Comments: The Authors are expected to address all the criticisms by all Reviewers. In particular, please clarify the study objectives and consider revising the title to fully reflect the study, define clearly symptoms compatible with COVID-19 (Reviewer #1), discuss study limitations and clarify selection of patients for serological test (Reviewer #2). In additional to the above comments, please address, 1. Supp Table 2, please align the serological test results with the correct occupation. 2. Please clarify if there were any nosocomial outbreaks in the University Health Network during the study period. [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: No ****** 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: Yes ****** 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: Dear authors, I read carefully your paper. In general my opinion about your work is positive. It is well-written, methodologically valid, the sample is adequate. Before to take a final decision about the publication I have few major concerns and some minor suggestions. Major concerns: • My first doubt concerns the structure and objectives of the article. In practice, it is as if numerous and different papers are included in your work. The main focus is the surveillance of HCWs. Then there are two secondary topics: the genetic sequencing of SARS-CoV-2, and the comparison of the performance of the different serological assays. These two secondary topics are not stated in the objectives, nor in the title, and are just mentioned in the introduction. I suggest to specify better the various topics that will be treated since from the introduction. Also, consider removing the information about genetic sequencing completely. This information is off-topic, and adds nothing to what is already known on the subject, even considering the low number of positive HCWs; • The second doubt is about the level of novelty and originality of the paper. Many reports about HCWs surveillance have been already published. Please better specify in the discussion which are the elements of novelty in your paper, and what your paper adds to the general knowledge about this topic. Minor suggestions: • You refer to asymptomatic HCW both in the title and in the short title. This suggest that the focus of your paper are asymptomatic HCWs only. This is not completely correct, because a relevant quote of symptomatic/pauci-symptomatic HCWs are included too. Please consider to revise the titles; • Among the objective it is listed “to determine the potential benefits of asymptomatic HCW screening in hospital settings”: this approach is already widely used, and many evidences (and the common sense) already validated it. I suggest removing this sentence from the objectives; • The sentence “Additional HCWs (asymptomatic or symptomatic) self-identified for voluntary screening through OHS” is unclear. Were these HCWs identified by OHS or by themselves? • About PPE used by HCWs, you refer that face shield are required for close contacts and N95 masks were used for aerosol-producing procedures. Do you refer to all patients or to suspected/confirmed COVID-19 patients only? • I suggest the remove the sentence “for an approximate infection rate of 0.25%”. To calculate the population infection rate you should know the real total number of infection, and not only those diagnosed; • In the Results, the cohort 2 was constituted by many HCWs who voluntary were tested for COVID-19. Was the recruitment period of this cohort the same as for cohort 1? The same 6 weeks period? • The third cohort is represented by HCWs who have “at least one symptom compatible with COVID-19”. You should define and list these symptoms; • Among studies in asymptomatic HCWs, consider to cite Fusco FM et al, COVID-19 among healthcare workers in a specialist infectious diseases setting in Naples, Southern Italy: results of a cross-sectional surveillance study. J Hosp Infect. 2020 Aug;105(4):596-600. In this study, as in your present paper, a combined PCR and serology approach has been used; • Please revise the alignment Supplementary Table 2, in the Occupation box. Reviewer #2: The Authors report on the experience of a Canadian tertiary care center to investigate asymptomatic COVID19 infections among healthcare workers. The topic is of high relevance right now and, while other similar reports have been published in literature, I think that this one should be shared as well. I have some comments: - limitations: I think the discussion should include better highlight limitations of the study. For example, this is not an universal screening beacuse only 1669 HCW out of 12.000 were enrolled. Is it possible that voluntary recruitment led to bias? - serology testing: the HCWs undergoing serology testing were from the 1669 people cohort enrolled for NF swabs? Figure 1 seems to suggest so, but it is not clear in the text. If yes, did they all tested negative on the NF swab? If now, was a NF swab performed in case of positive serology? Moreover, was IgM serology performed? If not why? How do you deal with positive IgG testing? We are still not sure of the timing of seroconversion. - female to male ratio: in the NF swabs cohort 1312 were female (vs. 356 males and 1 not binary) and in the serology cohort 781 were female (vs. 215 males). How do you comment this? Do you have mainly female HCWs in your hospital or females are more likely to undergo voluntary testing? - It would be nice to see if the positivity rate of the NF swab changes during the weeks accordingly with the general number of reported infection in the city and/or the hospital, as it was described in other reports on asymptomatic SARS-CoV-2 infections. ****** 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: Yes: Francesco Maria Fusco Reviewer #2: Yes:** Claudia Massarotti [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.0247258.r001
Revision 1
27 Jan 2021 Author Response PONE-D-20-34493 Prospective Observational Study of Screening Asymptomatic Healthcare Workers for SARS-CoV-2 at a Canadian Tertiary Care Center PLOS ONE Dear Academic Editor and Reviewers, We thank you for the time you have spent reviewing our manuscript and for your encouraging comments. Below you will find a point-by-point response to all critiques raised by the reviewers. Also attached is a separate file labeled “Revised Manuscript with Track Changes” with the revisions as suggested. Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Response: We have made the necessary revisions to meet the style guidelines. 2. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data. Response: We have removed the statement. It was not a core part of the research being presented. Additional Editor Comments: The Authors are expected to address all the criticisms by all Reviewers. In particular, please clarify the study objectives and consider revising the title to fully reflect the study, define clearly symptoms compatible with COVID-19 (Reviewer #1), discuss study limitations and clarify selection of patients for serological test (Reviewer #2). In additional to the above comments, please address, 1. Supp Table 2, please align the serological test results with the correct occupation. 2. Please clarify if there were any nosocomial outbreaks in the University Health Network during the study period. Response: We thank the Editorial Reviewer for highlighting these issues. We have addressed them all including a) revision to the title, b )inclusion of symptoms compatible with COVID, c) study limitations, d) clarifying selection of patients for serological testing, e) aligning serology with correct occupation, and b) nosocomial outbreaks during the study period. There were two outbreaks that were detected during this time due to participants testing positive in our study. This has been mentioned in the Discussion. We have also responded individually to each point below. Review Comments to the Author Reviewer #1: Dear authors, I read carefully your paper. In general my opinion about your work is positive. It is well-written, methodologically valid, the sample is adequate. Before to take a final decision about the publication I have few major concerns and some minor suggestions. Major concerns: • My first doubt concerns the structure and objectives of the article. In practice, it is as if numerous and different papers are included in your work. The main focus is the surveillance of HCWs. Then there are two secondary topics: the genetic sequencing of SARS-CoV-2, and the comparison of the performance of the different serological assays. These two secondary topics are not stated in the objectives, nor in the title, and are just mentioned in the introduction. I suggest to specify better the various topics that will be treated since from the introduction. Response: We have clarified the objectives and structure of the study in the Introduction. We also reworded the title to better illustrate the scope of the manuscript. We emphasized the fact that we were performing a serosurvey. We also clarified that the sequencing data was meant to complement the diagnostic PCR and made changes to the manuscript to reflect this. We hope this helps to better weave together the different components of the study. Also, consider removing the information about genetic sequencing completely. This information is off-topic, and adds nothing to what is already known on the subject, even considering the low number of positive HCWs; Response: We agree that the number of HCWs was low with regards to sequencing. However, we would respectfully like to keep this only as supplementary material as it helps to clarify whether PCR results may be falsely positive. For example, Sample 9 (Supp Table 3) had a negative convalescent antibody test result despite having a positive PCR. If we did not have supporting sequencing data, this sample could be misinterpreted as a PCR false positive. Because we have sequencing data for this sample, we can confirm presence of virus and failure to induce antibody responses, or perhaps antibody false-negative. • The second doubt is about the level of novelty and originality of the paper. Many reports about HCWs surveillance have been already published. Please better specify in the discussion which are the elements of novelty in your paper, and what your paper adds to the general knowledge about this topic. Response: We agree that other papers on HCW surveillance have been published. However, one very novel aspect of our study is using a microarray-based assay to determine protein-specific SARS-CoV-2 IgG antibodies. This is a novel adaptation of a platform which has not been described before. This is also the first data from a Canadian cohort. Minor suggestions: • You refer to asymptomatic HCW both in the title and in the short title. This suggest that the focus of your paper are asymptomatic HCWs only. This is not completely correct, because a relevant quote of symptomatic/pauci-symptomatic HCWs are included too. Please consider to revise the titles; Response: The focus of the study was in asymptomatic HCWs. We also included a cohort of symptomatic HCWs to compare rates of asymptomatic to symptomatic infection during the same window of time, however, the majority of the study, including the serosurvey, is primarily focused on asymptomatic HCWs. While there was reference to pauci-symptomatic individuals, we have reviewed the manuscript and made changes where appropriate to ensure language of the manuscript was precise. • Among the objective it is listed “to determine the potential benefits of asymptomatic HCW screening in hospital settings”: this approach is already widely used, and many evidences (and the common sense) already validated it. I suggest removing this sentence from the objectives; Response: We agree that asymptomatic screening of HCW is used at many centres, but its use is controversial at ours and other hospitals. We agree that other studies have provided some evidence for this. However, to garner evidence for asymptomatic screening was the initial goal of the study (since the study was done prior to start of asymptomatic screening at hospitals) and as such provides the evidence, we need to continue this practice. Therefore, we would respectfully like to keep this objective. • The sentence “Additional HCWs (asymptomatic or symptomatic) self-identified for voluntary screening through OHS” is unclear. Were these HCWs identified by OHS or by themselves? Response: These healthcare workers voluntarily appeared for screening at occupational health and safety. During this time, our center offered voluntary screening for any HCW, regardless of symptoms. We have now clarified this detail in the Materials and methods. • About PPE used by HCWs, you refer that face shield are required for close contacts and N95 masks were used for aerosol-producing procedures. Do you refer to all patients or to suspected/confirmed COVID-19 patients only? Response: Face shield and surgical mask were required for all patient contact regardless of COVID positivity. N95 were required for aerosol generating procedures with all patients regardless of COVID positivity. • I suggest the remove the sentence “for an approximate infection rate of 0.25%”. To calculate the population infection rate you should know the real total number of infection, and not only those diagnosed; Response: We thank the reviewer for this and have removed the statement as suggested. • In the Results, the cohort 2 was constituted by many HCWs who voluntary were tested for COVID-19. Was the recruitment period of this cohort the same as for cohort 1? The same 6 weeks period? Response: Yes, all participants were recruited from the same 6-week period of time as cohort 1. We have emphasized this point in the revision. • The third cohort is represented by HCWs who have “at least one symptom compatible with COVID-19”. You should define and list these symptoms; Response: Symptoms compatible with COVID-19 included: fever, headache, new or worsening cough, shortness of breath, sore throat, rhinorrhea, diarrhea, anosmia, myalgias, and conjunctivitis. This information has now been added to the Materials and methods section. • Among studies in asymptomatic HCWs, consider to cite Fusco FM et al, COVID-19 among healthcare workers in a specialist infectious diseases setting in Naples, Southern Italy: results of a cross-sectional surveillance study. J Hosp Infect. 2020 Aug;105(4):596-600. In this study, as in your present paper, a combined PCR and serology approach has been used; Response: Thank you for bringing this study to our attention. We have added a reference to this paper in the discussion. • Please revise the alignment Supplementary Table 2, in the Occupation box. Response: We have properly aligned the table, as requested. Apologies for this oversight. Reviewer #2: The Authors report on the experience of a Canadian tertiary care center to investigate asymptomatic COVID19 infections among healthcare workers. The topic is of high relevance right now and, while other similar reports have been published in literature, I think that this one should be shared as well. Response: We thank the reviewer for this encouraging remark. I have some comments: - limitations: I think the discussion should include better highlight limitations of the study. For example, this is not an universal screening beacuse only 1669 HCW out of 12.000 were enrolled. Is it possible that voluntary recruitment led to bias? Response: The reviewer is correct in pointing out that this was not universal screening. It was a prospective study where HCW were required to consent to participate. It was near the start of the pandemic in Canada where asymptomatic screening was not standard of care. Therefore, through a study, we sought to determine the utility of asymptomatic screening. The participants were therefore those that volunteered to participate and may be different than those that did not participate. However, we sampled a significant proportion of our HCWs (14%) so believe the risk of bias is low. Nevertheless, we have added this point to the limitations section in the Discussion. - serology testing: the HCWs undergoing serology testing were from the 1669 people cohort enrolled for NF swabs? Figure 1 seems to suggest so, but it is not clear in the text. If yes, did they all tested negative on the NF swab? If now, was a NF swab performed in case of positive serology? Moreover, was IgM serology performed? If not why? How do you deal with positive IgG testing? We are still not sure of the timing of seroconversion. Response: We have made sure to clarify that the serosurvey was performed exclusively on a subset of consenting HCWs from cohort 1 (ie those enrolled for NF swabs). Blood collection for antibody testing and swab collection were performed at the same time. Only one asymptomatic HCW who tested positive for SARS-CoV-2 had serology drawn the same day of their positive PCR. Initial serology was negative but upon follow-up antibody testing several weeks later, this HCW became seropositive. The remainder of nasopharyngeal swabs were negative. IgM serology was not performed. At the time of the study, the majority of validated commercial antibody tests were for IgG antibodies. Neutralizing antibodies are also of the IgG isotype so this information may be of more clinically relevant than IgM. The IgM response also appears to decline much faster (Dan et al., 2021; Science). As such, we focussed primarily on IgG responses. Those with positive IgG testing, and negative contemporaneous PCR, are discussed in Supp Table 4. These HCWs were felt to have past resolved infection since all had negative nasopharyngeal swabs as well. - female to male ratio: in the NF swabs cohort 1312 were female (vs. 356 males and 1 not binary) and in the serology cohort 781 were female (vs. 215 males). How do you comment this? Do you have mainly female HCWs in your hospital or females are more likely to undergo voluntary testing? Response: Yes, at UHN 73% of HCWs are female (https://www.uhn.ca/corporate/AboutUHN/Pages/uhn_at_a_glance.aspx#research). We believe this explains the significant discrepancies in sex. - It would be nice to see if the positivity rate of the NF swab changes during the weeks accordingly with the general number of reported infection in the city and/or the hospital, as it was described in other reports on asymptomatic SARS-CoV-2 infections. Response: We agree that this would be of interest. The number of swabs over the 6 weeks were overall evenly distributed over the six weeks of the study. However, due to the overall small number of positives among asymptomatic HCWs, we do not think a formal analysis is possible. Greater numbers of cases would likely be required to appropriately make this valuable comparison. Attachments Attachment Submitted filename: PLOS ONE Response to Reviewers -dk.docx https://doi.org/10.1371/journal.pone.0247258.r002
4 Feb 2021 Decision Letter - Eric HY Lau, Editor Prospective observational study and serosurvey of SARS-CoV-2 infection in asymptomatic healthcare workers at a Canadian tertiary care center PONE-D-20-34493R1 Dear Dr. Ferreira, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Eric HY Lau, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): 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 #2: 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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 #2: 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 #2: 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: (No Response) Reviewer #2: I am satisfied with the answers to my previous remarks and I therefore recommend the article for publication. ****** 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 #2: Yes:** Claudia Massarotti https://doi.org/10.1371/journal.pone.0247258.r003
Formally Accepted
5 Feb 2021 Acceptance Letter - Eric HY Lau, Editor PONE-D-20-34493R1 Prospective observational study and serosurvey of SARS-CoV-2 infection in asymptomatic healthcare workers at a Canadian tertiary care center Dear Dr. Ferreira: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Eric HY Lau Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0247258.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .