PONE-D-22-18040Pregnant women with mild COVID-19 followed in community setting by telemedicine, and factors associated with unfavorable outcomePLOS ONE

Dear Dr. Dinh,

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

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Burak Bayraktar

Academic Editor

PLOS ONE

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4. One of the noted authors is a group or consortium [the AP-HP/Universities/Inserm COVID-19 research collaboration]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address

Additional Editor Comments:

1. Introduction is short. Expand this section a bit.

In addition;

Provide information about telemedicine in one paragraph, as well as mention its uses and why it is appropriate in the COVID era. You can talk about the advantages of telemedicine in this period.

2. “Covidom includes a web application sending daily questionnaires to patients and a regional control center dealing with alerts generated by the response to questionnaires” How to make covidom, talk a little more.

3. Separate the statistical analysis paragraph as a subtitle: Statistical Analysis

4. “Child death 6 (11)” Include indications of death where possible.

5. Add Table 2 to results section (no discussion)

6. “Thus, surprisingly, our population of women with mild COVID-19 seems to have around the same rate of fetal adverse outcome than the general population” How is this situation in the literature?

7. “In our study, the other risk factor associated with adverse fetal outcome was pregnancy- induced hypertension. These results should lead to increase monitoring among pregnant women with COVID-19 if hypertension occurs.” Any ideas on the mechanism? Similar results are available in the literature. What do you think?

8. Do not analyze each research result in a separate paragraph in the Discussion section. Make a single paragraph of conclusions on similar topics.

9. Can the results regarding the periods of catching COVID 19 (first-second and third trimester) of pregnant women change? I guess you didn't group according to trimesters.

10. Indicate that you are only including mild cases of COVID 19 in the material method, where appropriate.

11. I did not see information about the vaccination status in your population.

12. Discussion section should be more organized.

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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?

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

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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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: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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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

Reviewer #5: Yes

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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: A very well done project.

I would suggest adding information related to other perinatal outcomes that have already been shown to increase in prevalence as a sequela of COVID infection, e.g., preeclamsia (early/tardia), placental abruption.

Reviewer #2: 1. Was there cross over from those who consented to telemedicine to in-person consult? From the results, it seemed that 100% of the participants had remained on telemedicine follow up. If so, probably can describe in more detail in the discussion why you were able to keep them well managed on telemedicine. How did you pick up the worsening of symptoms. Were you able to remotely measure parameters or examine the patient?

2. Besides the COVID-19 follow up, was the Ob/Gyn follow up also on telemedicine/hybrid or it was purely in person?

3. From what i understand, there is a pretty large group 55.7% (pregnant with mild COVID-19) that was on follow up with the health system but did not consent to telemedicine follow up. I thought it would have been useful to compare the 44.3% that had underwent telemedicine guided by the daily self-reporting of symptoms and whether it made a difference compared to those who only came for in-person follow ups when they were unwell, or as a routine.

4. Specifically for PIH, it did show a significant difference for adverse outcomes as defined by the study. It was not clear COVID-19 worsened the incidence of adverse outcomes or not. From my limited understanding, even without COVID-19 infection, those with PIH could have pre-eclampsia leading to SGA, IUGR, indicated pre-term deliveries already.

Reviewer #3: Thank you for your wonderful efforts and hard work that is clearly reflected in your project.

I may highlight these points, not to decline your work, but to have a better view of the project outcomes.

I am happy to reconsider your work after making some clarifications on these points:

1- Correlation between the time that the patient had COVID-19 and her gestational age? and was there any difference between different gestational ages and the outcome?

2- When you describe mild COVID-19, can you please identify all the criteria and clinical symptoms that made you consider it as mild COVID?

3- Duration between having COVID and the outcome. i.e: Can you highlight timelines? if the patient had COVID-19 (mild symptoms) when exactly she either delivered, had a preterm delivery, or had a stillbirth?

4- What do you mean by chest oppression in lines 97 & 138?

5 - Have the patients who had PIH, developed it after COVID-19 or before?

6 - Any of these ladies got vaccinations or not?

7- Any other factors that was contributing to the outcome? for example: when you mentioned stillbirth or preterm, do you know if any previous obstetric history of the same issues?

8- Any ultrasound or Doppler studies done for these patients, either before, during, or after having COVID, that identified any fetal issues?

Reviewer #4: This manuscript seems smart and clear with several meaningful tables. To my disappointed, these data are obtained from self-reported informations, which have many limitations.

For example, in case that pregnant women suffering from COVID-19 infection requires some medications, the kind of drug and the dose may be more influenced to the fetal outcomes.

After reading this manuscript, I have two requests shown as follows;

#1. Although statistic significant difference are shown undoubtedly, the number of fetal death seems much close between hospitalization group (1/102) and non-hospitalization one (5/612). The rate of pregnancy-induced hypertension are not significant differences between these two groups, so I would like you to disclose more information about these six cases such as weeks of delivery and the existence of fetal distress.

#2. In discussion you mentioned the relation between the ICU admission of newborn children and the vaccination of COVID-19. We must desire to know about the relation in this Covidom research. If you have already evaluated the relation, please let us show that.

Reviewer #5: 1. ABSTRACT: The abstract should start with a brief background to the study highlighting what is known or unknown about the proposed study.

Objective: The word “we” should be removed from the objective

Methods: The information doesn’t convey succinctly how the study was done.

Conclusion: Conclusion should also be made on the role or impact of telemedicine

2. The introduction is too short and doesn’t state the extent of the problem neither does it contain the justification for the study. A more elaborate introduction should be written.

3, The methodology should describe in details what the COVIDOM telemedicine software is all about. How does it work? What version was used for this study? Is it a video conferencing or audio-conferencing app? This information should be clearly spelt out in the methodology

4. The methodology should describe in details how the telemedicine was used for the study. How were the questionnaires delivered? Was it delivered to their phones or email? Was there an online/web based face-to-face interview?

5 Lines 114,115,116-- Pregnant women with severe COVID-19 had higher risk of preeclampsia, preterm birth, gestational diabetes, and low birthweight than pregnant women with mild disease. This outcome is expected.

6. Table 2 should be moved to the result section

7. The study involved the use of telemedicine. Was there any advantage regarding the use of telemedicine over other studies that telemedicine was not used? There should be a robust discussion on telemedicine.

8. The references were not properly written. Almost all the references still have the DOI numbers. They should be rewritten according to Vancouver guidelines.

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Reviewer #1: Yes: Borboa Olivares Hector

Reviewer #2: No

Reviewer #3: Yes: Mena Abdalla

Reviewer #4: No

Reviewer #5: No

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Pregnant women with mild COVID-19 followed in community setting by telemedicine, and factors associated with unfavorable outcome

PONE-D-22-18040R1

Dear Dr. Dinh,

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,

Burak Bayraktar

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 #2: All comments have been addressed

Reviewer #5: All comments have been addressed

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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 #2: Yes

Reviewer #5: Yes

**********

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

Reviewer #2: Yes

Reviewer #5: 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 #2: Yes

Reviewer #5: Yes

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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 #2: Yes

Reviewer #5: 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 #2: Thanks to the authors for making the edits. It looks clearer, organised and is much more informative now.

Reviewer #5: All comments have been addressed. However the abstract should start with "Background" and not Objective.

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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 #2: No

Reviewer #5: No

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