Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France

Jérémie Mattern; Christelle Vauloup-Fellous; Hoda Zakaria; Alexandra Benachi; Julie Carrara; Alexandra Letourneau; Nadège Bourgeois-Nicolaos; Daniele De Luca; Florence Doucet-Populaire; Alexandre J. Vivanti

doi:10.1371/journal.pone.0240782

Peer Review History

Original SubmissionJuly 7, 2020
7 Aug 2020 Decision Letter - Frank T. Spradley, Editor PONE-D-20-20995 Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France PLOS ONE Dear Dr. Vivanti, 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. Four experts in the field handled your manuscript. We are thankful for their time and efforts. Although some interest was found in your study, several major comments arose that overshadowed this enthusiasm. These comments include that: several statements need citations; there are concerns about specifics of diagnosis and testing for COVID-19; numerous questions about the study design, including how the women were experimentally grouped and sensitivity of assays; the data presentation needs work, including the inclusion of data for the local evaluations; the discussion needs to be more developed; and the conclusions should better reflect the findings. ALL of the reviewers' comments must be addressed in your revised manuscript. Please submit your revised manuscript by Sep 21 2020 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, Frank T. Spradley 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 indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 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: Partly Reviewer #2: Yes Reviewer #3: Partly Reviewer #4: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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: Yes Reviewer #3: No Reviewer #4: 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 Reviewer #3: Yes Reviewer #4: 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: The background and methods of this study are very good. It is impressive that you have managed to collect this amount of data for such a specific patient demographic. The data analysis has also been performed well. I feel however that the discussion needs to have more detail. Furthermore, you have only written your conclusion in the abstract; you also need a conclusion section in the main body of the manuscript. The conclusion you have reached is that SARS-Cov-2 negative women need to be taken into consideration in case of a second wave. However, I feel that you need more justification of this stance. Your results state that 47.4% of the positive women did not have any symptoms and those who did have symptoms appear relatively mild. Furthermore, your results also state that the majority of women were uninfected. Did you find any serious sequelae of SARS-CoV-2 infection in your study as a whole? If yes, you need to include this. If not, then how have you come to the conclusion that these patients require more consideration than the general population? In summary, you need to do further work in your discussion, because your actual results do not really justify your conclusion. You need to elaborate further on the potential consequences of SARS-CoV-2 infection in pregnant women if this is the conclusion you have made, and this requires more research into maternal and neonatal morbidity and mortality due to SARS-CoV-2. You need to compare and contrast your results to other research on this topic, and write a discussion that properly debates whether pregnancy puts mothers and neonates at higher risk of death or not. Reviewer #2: Review: “Post lockdown COVID-19 seroprevalence and circulation at the time of delivery,France” General comments: This is a research involving the first wave of the COVID-19 pandemic in Paris and the effect of lockdown on seroprevalence in your maternity ward, which has been significantly affected by the virus (more than 40 confirmed infections among pregnant women between March 12 and April 20). Pregnancy as a severity risk factor of severe acute respiratory syndrome coronavirus 2 77 (SARS-CoV-2) infection is still debated.This study prospectively to evaluate the impact of the first wave of the COVID-19 pandemic at the Antoine Béclère Hospital maternity ward (Paris area, France) from May 4 (one week before the end of lockdown) to May 31, 2020 86 (three weeks after the end of lockdown). I recommend a publication of this paper with major revisions. Abstract: 1.Study design:“All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well concomitant SARS-CoV-2 RT-PCR on a nasopharyngeal sample”.As we all known, Throat swab nucleic acid positive rate is low,how many times do your study deign If the first nucleic acid test is negative? 2.Result: “A history of symptoms during the epidemic, such as fever, 54 myalgia and anosmia, was suggestive of previous infection.” What is the distribution of various clinical symptoms. Key words: Please add on. Introduction: 1.The introduction is too simple to state the current studies of COVID-19. 2.“more than 40 confirmed infections among pregnant women between March 12 and April 20”，Do you have some references? Materials and Methods: 1.“All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well as SARS-CoV-2 RT-PCR on a nasopharyngeal sample”. Did the serological testing include IgM and why it is’t mentioned in the full text? 2.“All data (clinical, laboratory, from both mothers and newborns) were prospectively collected from medical records.” This is a prospective study. Have you list which laboratory indicators need to be tested? Results: 1. “Only one (0.5%) test was positive and this 143 patient remained asymptomatic during delivery and early post-partum”, Does this patient have a CT scan and how about the Image performance? Reviewer #3: “Post lockdown COVID-19 seroprevalence and circulation at the time of 1 delivery, France” reported that the positive rates of SARS-COV2 IgG and virus RNA of throat samples in group of patients in maternity ward around the end of LOCKdown timepoints. Although the data is convincing, it does not look conclusive since no data was shown the positive rates before the end of lockdown(ie. 14 days before lockdown; lockdown periods, postlockdown). Secondly, except that the only diagnosed patients were both RNAand IgG positive and had symptoms and epidemiological evidence, no current infections of SARS-COV-2 were completely tested for all other patients since no IgM test were performed(sensitivity of RNA detection is usually low). So , the conclusion that the virus was no longer circulating up to three weeks after the end of the lockdown may not be acurate. Thirdly. “ half of the SARS-CoV-2-IgG-positive pregnant women were completely asymptomatic “may not be acurate since a longer time (more than 5 months )of history of symptoms may be required. Therefore I do not think the manuscript merit to publish in Plos one Journal unless these issues are resolved. However, the conclusion that “a high proportion of SARS-CoV-2-IgG-negative pregnant women must be taken into into consideration in the event of a resurgence of the pandemic...” is helpful. Reviewer #4: The authors have investigated an important issue for the field of obstetrics during the current pandemic. The reasoning behind and the research set up is sound. The results have additional value and provide insights into the clinical presentation and pathogenesis of COVID19 during pregnancy. Comments: Line 71-72: reference is missing Line 73: reference is missing Line 77-78 Please do explain the third trimester is a consensual factor for SARS-CoV-2 infection, including reference. Line 79: the effect of the lockdown: how is the effect exactly investigated or evaluated? Line 99: why not show the data of the local evaluation. This will added to the impact of the results. Is there a control group, on what is the threshold of < 0.8 based? Lin 106: what is Cepheid, where is it based? Line 107: why use different assay? What is the difference in sensitivity between assay or it there none? Line 145: perhaps elaborate on the CT value, based on the used assay. Line 161: how come 3 women report anosmia (in general)? Does this occur often in Paris? Line 164: which group did the woman who did not respect the lockdown belong to? Line 173: were they also asymptomatic during possible infection? With positive seroprevalence, one can assume she was post-infection. Meaning: did they report symptoms at any time? Do pregnant women have asymptomatic infection? Discussion. There should be more details about the IgG-positive women and possible presentation, effect, risks and implications for pregnancy and hypotheses behind. What are the recommendation at a second wave based on the results. ****** 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:** Shuliang Oliver Cheng Reviewer #2: No Reviewer #3: No Reviewer #4: 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. Attachments Attachment Submitted filename: Review of Post lockdown COVID.docx https://doi.org/10.1371/journal.pone.0240782.r001
Revision 1
10 Sep 2020 Author Response Clamart, September 7, 2020 Dear Editor, Thank you for the opportunity to revise our paper. On behalf of all authors, I’m sending you a revised version of our manuscript entitled “Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France”. We have carefully considered the suggestions and comments of the reviewers to improve the quality of our work. We are willing to provide other changes or clarification if you so wish. We hope that this revised version of the manuscript will still be considered for publication in Plos One. Thank you again for your work, Yours sincerely, Alexandre VIVANTI (MD, PhD) Reviewer #1 The background and methods of this study are very good. It is impressive that you have managed to collect this amount of data for such a specific patient demographic. The data analysis has also been performed well. I feel however that the discussion needs to have more detail. Furthermore, you have only written your conclusion in the abstract; you also need a conclusion section in the main body of the manuscript. Thank you for your comments. We have added a conclusion to the main text of the manuscript. The conclusion you have reached is that SARS-Cov-2 negative women need to be taken into consideration in case of a second wave. However, I feel that you need more justification of this stance. Your results state that 47.4% of the positive women did not have any symptoms and those who did have symptoms appear relatively mild. Furthermore, your results also state that the majority of women were uninfected. Did you find any serious sequelae of SARS-CoV-2 infection in your study as a whole? If yes, you need to include this. If not, then how have you come to the conclusion that these patients require more consideration than the general population? The design of our study did not allow us to assess the existence of sequelae in our patient population. However, it has recently been shown that pregnancy in the 2nd and 3rd trimesters represents an independent risk factor for oxygen therapy, hospitalization in an intensive care unit and use of mechanical ventilation (1,2). It is important to note that pregnant women are subject to specific recommendations to limit the risk of infection and it appears that seroprevalence, although not high, is similar to that observed in the general population at the same time. For these reasons, it is imperative that special attention be paid to this at-risk population in the event of a second wave of infections. We have provided further details in the manuscript. 1) Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD, et al. Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020. MMWR Morb Mortal Wkly Rep. 2020;69: 769–775. doi:10.15585/mmwr.mm6925a1 2) Badr DA, Mattern J, Carlin A, Cordier A-G, Maillart E, Hachem LE, et al. Are clinical outcomes worse for pregnant women ≥ 20 weeks’ gestation infected with COVID-19? A multicenter case-control study with propensity score matching. American Journal of Obstetrics & Gynecology. 2020;0. doi:10.1016/j.ajog.2020.07.045 In summary, you need to do further work in your discussion, because your actual results do not really justify your conclusion. You need to elaborate further on the potential consequences of SARS-CoV-2 infection in pregnant women if this is the conclusion you have made, and this requires more research into maternal and neonatal morbidity and mortality due to SARS-CoV-2. You need to compare and contrast your results to other research on this topic, and write a discussion that properly debates whether pregnancy puts mothers and neonates at higher risk of death or not. Consistent with your suggestions, we have enhanced the discussion in relation to recent data in the literature. Reviewer #2 Review: “Post lockdown COVID-19 seroprevalence and circulation at the time of delivery,France” General comments: This is a research involving the first wave of the COVID-19 pandemic in Paris and the effect of lockdown on seroprevalence in your maternity ward, which has been significantly affected by the virus (more than 40 confirmed infections among pregnant women between March 12 and April 20). Pregnancy as a severity risk factor of severe acute respiratory syndrome coronavirus 2 77 (SARS-CoV-2) infection is still debated. This study prospectively to evaluate the impact of the first wave of the COVID-19 pandemic at the Antoine Béclère Hospital maternity ward (Paris area, France) from May 4 (one week before the end of lockdown) to May 31, 2020 86 (three weeks after the end of lockdown). I recommend a publication of this paper with major revisions. Abstract: 1.Study design:“All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well concomitant SARS-CoV-2 RT-PCR on a nasopharyngeal sample”. As we all known, Throat swab nucleic acid positive rate is low,how many times do your study deign If the first nucleic acid test is negative? Indeed, the sensitivity of the PCR is considered average (60-80%). As this is a routine screening in a population of asymptomatic women, we performed only one nasopharyngeal swab. In our opinion, multiple tests can be considered when there is a strong clinical presumption. We have added details to the abstract. 2.Result: “A history of symptoms during the epidemic, such as fever, 54 myalgia and anosmia, was suggestive of previous infection.” What is the distribution of various clinical symptoms. A history of symptoms during the epidemic, such as fever (15.8%), myalgia (36.8%) and anosmia (31.6%), was suggestive of previous infection. Details added to the abstract Key words: Please add on. Keywords added: Pregnancy, SARS-CoV-2, Covid-19, Seroprevalence, RT-PCR Introduction: 1.The introduction is too simple to state the current studies of COVID-19. We have provided more information about the issues that justify a seroprevalence study in pregnant women. 2.“more than 40 confirmed infections among pregnant women between March 12 and April 20”，Do you have some references? Pregnant patients in our maternity ward who were infected with SARS-CoV-2 were the subject of a publication. We have provided the reference in the manuscript. Vivanti AJ, Mattern J, Vauloup-Fellous C, Jani J, Rigonnot L, El Hachem L, et al. Retrospective description of 100 pregnant women with SARS-CoV-2 infection, France. Emerg Infect Dis. 2020. Materials and Methods: 1.“All patients admitted to the delivery room during this period were offered a SARS-CoV-2 serology test as well as SARS-CoV-2 RT-PCR on a nasopharyngeal sample”. Did the serological testing include IgM and why it is’t mentioned in the full text? The serological test did not not include IgM. Mention added. 2.“All data (clinical, laboratory, from both mothers and newborns) were prospectively collected from medical records.” This is a prospective study. Have you list which laboratory indicators need to be tested? Only serological data and RT-PCR results were collected. Results: 1. “Only one (0.5%) test was positive and this 143 patient remained asymptomatic during delivery and early post-partum”, Does this patient have a CT scan and how about the Image performance? The patient did not have a CT scan. In our center, patients with a positive RT-PCR test with no sign of severity do not undergo a CT scan. The design of our study does not allow us to evaluate the performance of the scanner in pregnant women infected with COVID-19. Reviewer #3 “Post lockdown COVID-19 seroprevalence and circulation at the time of 1 delivery, France” reported that the positive rates of SARS-COV2 IgG and virus RNA of throat samples in group of patients in maternity ward around the end of LOCKdown timepoints. Although the data is convincing, it does not look conclusive since no data was shown the positive rates before the end of lockdownc(ie. 14 days before lockdown; lockdown periods, postlockdown). We didn’t test all the patients during the lockdown (only symptomatic women), so we didn’t have the previous positive rate, but we assumed that this one was much higher. Secondly, except that the only diagnosed patients were both RNA and IgG positive and had symptoms and epidemiological evidence, no current infections of SARS-COV-2 were completely tested for all other patients since no IgM test were performed (sensitivity of RNA detection is usually low). So, the conclusion that the virus was no longer circulating up to three weeks after the end of the lockdown may not be acurate. You are right, RT-PCR sensitivity must be taken into account. However, we used the same RT-PCR test that resulted in the diagnosis of over 40 patients with symptoms related to the 15/03 -18/04 period. Even taking into account a sensitivity of 60% of the RT-PCR test (low range), one could imagine that the detection of IgM could have allowed diagnosis for one more patient. We have, however, tempered the conclusions regarding the non-circulation of the virus. Thirdly. “ half of the SARS-CoV-2-IgG-positive pregnant women were completely asymptomatic “may not be acurate since a longer time (more than 5 months) of history of symptoms may be required. We do not fully agree with this assertion, since to date no robust published data have defined the monitoring period that enables us to assert the absence of symptoms/sequelae. Consistent with your suggestion, we mention that the absence of symptoms was related to the duration of the study. Therefore I do not think the manuscript merit to publish in Plos one Journal unless these issues are resolved. However, the conclusion that “a high proportion of SARS-CoV-2-IgG-negative pregnant women must be taken into into consideration in the event of a resurgence of the pandemic...” is helpful. Reviewer #4 The authors have investigated an important issue for the field of obstetrics during the current pandemic. The reasoning behind and the research set up is sound. The results have additional value and provide insights into the clinical presentation and pathogenesis of COVID19 during pregnancy. Comments: Line 71-72: reference is missing Added Line 73: reference is missing Added Line 77-78 Please do explain the third trimester is a consensual factor for SARS-CoV-2 infection, including reference. It has recently been shown that pregnancy in the 2nd and 3rd trimesters represents an independent risk factor for oxygen therapy, hospitalization in an intensive care unit and use of mechanical ventilation. These data are from case-control studies using a propensity score, which allows a robust response regarding the involvement of pregnancy as an independent risk factor. 1) Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD, et al. Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020. MMWR Morb Mortal Wkly Rep. 2020;69: 769–775. doi:10.15585/mmwr.mm6925a1 2) Badr DA, Mattern J, Carlin A, Cordier A-G, Maillart E, Hachem LE, et al. Are clinical outcomes worse for pregnant women ≥ 20 weeks’ gestation infected with COVID-19? A multicenter case-control study with propensity score matching. American Journal of Obstetrics & Gynecology. 2020;0. doi:10.1016/j.ajog.2020.07.045 Line 79: the effect of the lockdown: how is the effect exactly investigated or evaluated? Lockdown has been shown to result in a very significant decrease in the incidence of COVID-19 infections in pregnant women in France. Kayem G, Alessandrini V, Azria E, Blanc J, Bohec C, Bornes M, et al. A snapshot of the Covid-19 pandemic among pregnant women in France. Journal of Gynecology Obstetrics and Human Reproduction. 2020; 101826. doi:10.1016/j.jogoh.2020.101826 We aimed to evaluate the effects of the lifting of lockdown on a possible increase of the incidence of COVID-19 infection rates. We provide extra information throughout the manuscript. Line 99: why not show the data of the local evaluation. This will added to the impact of the results. Is there a control group, on what is the threshold of < 0.8 based? The data are from a large cohort of patients. A control group is required to set a threshold. These data will be submitted for publication. A manuscript is in preparation Lin 106: what is Cepheid, where is it based? Cepheid is an American molecular diagnostics company based in California, USA. We have detailed this in the manuscript. Line 107: why use different assay? What is the difference in sensitivity between assay or it there none? We adapted our algorithm of the assay choice to our workflow, to our reagent supply possibilities and to the urgency of the results for clinical management of some parturients. We now mention this in the manuscript The GeneFinder assay was used as our routine test during the day and this technique requires personnel qualified in molecular biology and a relatively high turnaround time (4 hours). We specify this in the manuscript: It was used as our routine test during the day. The Xpert Xpress SARS-CoV-2 assay (Cepheid) and the GenMark ePlex SARS-CoV-2 assay (ELItech) are two platforms that integrate specimen processing, nucleic acid extraction and reverse transcription PCR. Samples can be tested as soon as they are received, and results are generated in about 45 min. They were used during the night, on weekends and for urgent results. We now mention this in the manuscript All assays used have the same analytical performances. Line 145: perhaps elaborate on the CT value, based on the used assay. Only one PCR was positive and only nucleocapsid (N2) gene was detected at a CT value of 41.4 within the valid range and an endpoint above the minimum setting of this FDA-approved assay. This indicates that the viral load of the sample is at the limit of detection of the Xpert Xpress assay. We now mention this in the manuscript Loeffelholz MJ, Alland D, Butler-Wu SM, Pandey U, Perno CF, Nava A, Carroll KC, Mostafa H, Davies E, McEwan A, Rakeman JL, Fowler RC, Pawlotsky JM, Fourati S, Banik S, Banada PP, Swaminathan S, Chakravorty S, Kwiatkowski RW, Chu VC, Kop J, Gaur R, Sin MLY, Nguyen D, Singh S, Zhang N, Persing DH. Multicenter Evaluation of the Cepheid Xpert Xpress SARS-CoV-2 Test. J Clin Microbiol 2020 23;58(8):e00926-20. doi: 10.1128/JCM.00926-20. Line 161: how come 3 women report anosmia (in general)? Does this occur often in Paris? We have not particularly explored these specific patient responses. We do not have any data that could lead us to believe that anosmia often happens in Paris, but we can report that this symptom has been highly publicized in France. These reported symptoms may come from impressions reinforced by the strong media coverage of anosmia during the peak of the epidemic, making this benign symptom a potential marker of an infection encountered just before lockdown. It could also be the result of false-negative IgG test Line 164: which group did the woman who did not respect the lockdown belong to? She belonged to the negative group (now specified). Line 173: were they also asymptomatic during possible infection? With positive seroprevalence, one can assume she was post-infection. Meaning: did they report symptoms at any time? Do pregnant women have asymptomatic infection? Patients from this cohort have reported any symptoms occurring from January 1st. We have no reason to think that pregnant patients have more asymptomatic infections than the general population. Rather, the tendency is to believe that pregnancy increases the severity of symptoms. The test used to assess the presence of SARS-CoV-2 IgG is a commercial chemiluminescent immunoassay validated for clinical use by the FDA with high analytical and clinical performances. Ref: Bryan A, Pepper G, Wener MH, Fink SL, Morishima C, Chaudhary A, Jerome KR, Mathias PC, Greninger AL. Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho. J Clin Microbiol. 2020 Jul 23;58(8):e00941-20. EUA Authorized Serology Test Performance. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance) In just the past few months, multiple studies have characterized the kinetics of IgM and IgG, in the immune response to SARS-CoV-2 infection. IgM antibodies are readily produced as early as 1 day after infection, and the time of IgG seroconversion is expected to be in the range of 7 to 14 days after the onset of symptoms. However, Okba et al. reported that IgG and IgA kinetics depended on disease severity, and especially that patients with more severe disease developed an antibody response sooner and in higher concentrations. As our patients had mild symptoms, a late seroconversion is possible. Unfortunately, sera collected later were not available. Ref: Wang Y, Zhang L, Sang L. Kinetics of viral load and Antibody Responses in relation to COVID-19 severity. J Clin Invest. 2020; 138759. DOI: 10.1172/JCI138759. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581(7809): 465-9. DOI: 10.1038/s41586-020-2196-x Long QX, Liu BZ, Deng HJ, et al. Antibody responses to SARS-CoV-2 in patients with COVID19. Nature Med 2020; 26(6): 845-8. DOI: 10.1038/s41591-020-0897-1. Okba NMA, Müller MA, Li W, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients. Emerg Infect Dis. 2020; 26(7): 1478-88. DOI: 10.3201/eid2607.200841 Discussion. There should be more details about the IgG-positive women and possible presentation, effect, risks and implications for pregnancy and hypotheses behind. What are the recommendation at a second wave based on the results. We have added extra explanations to the discussion section Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0240782.r002
5 Oct 2020 Decision Letter - Frank T. Spradley, Editor Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France PONE-D-20-20995R1 Dear Dr. Vivanti, 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, Frank T. Spradley Academic Editor PLOS ONE 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: 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 #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: Thank you for adding to the discussion and highlighting recommendations that ought to be made to pregnant women to reduce transmission of SARS-CoV-2. Furthermore, thank you for highlighting the added risk due to pregnancy of severe sequelae of SARS-CoV-2 infection. Reviewer #3: The author has answered all the questions and I recommend publication of this manuscript in Plos One ****** 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: Yes:** Shuliang Oliver Cheng Reviewer #3: No Attachments Attachment Submitted filename: Dear Editor.docx https://doi.org/10.1371/journal.pone.0240782.r003
Formally Accepted
7 Oct 2020 Acceptance Letter - Frank T. Spradley, Editor PONE-D-20-20995R1 Post lockdown COVID-19 seroprevalence and circulation at the time of delivery, France Dear Dr. Vivanti: 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. Frank T. Spradley Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0240782.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 .