PONE-D-22-08926Cardiovascular diseases worsen the maternal prognosis of COVID-19PLOS ONE

Dear Dr. Luciana Graziela de Godoi,

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

Please carefully consider all of the reviewers’ comments, criticisms and suggestions below particularly confirmed diagnosis of COVID-19 and the definition of cardiovascular diseases and several others that are required to define clearly. In addition, please carefully follow all comments concerning methodology, statistical analysis, results, conclusions and limitations of the study.

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Vipa Thanachartwet, M.D.

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?

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

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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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

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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

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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: This is an observational study with a large sample size on the evaluation whether the presence of CVD in pregnant women and in postpartum women with COVID-19 is associated with a worse prognosis. Authors used an anonymized open database. They concluded that “Hospitalized obstetric patients with CVD and COVID-19 are more symptomatic.” and that “Their management demand more ICU admission and ventilatory support and the mortality is higher.”

I think that this is a publishable work, but I have some points that need reconsideration.

In the abstract, as in the whole text, there must be clearer distinctions for the groups studied and compared.

In the introduction section, the rationale should be revisited. The aim of the study should be clearly stated in the last sentence.

In the materials and methods, parts from there should be moved in the introduction section; authors should make clear what their comparisons should be and the exact methods; this should be followed in all the next sections, for the reader to understand exactly the correlations. The hospitalized COVID positive patients could be divided according to trimesters (as the results show afterwards), to their state (for e.g. incubated or not e.t.c), days of hospitalization, of NICU stay etc.; other comorbidities should be discriminated – for example a subgroup analysis there might be of essence.

The results should contain the exact results of the comparisons.

The limitations of the study should be presented.

The conclusions should adhere to the exact aim, findings and type of the study presented.

Reviewer #2: The authors present convincing data on the worse prognosis of pregnant women with COVID-19 infection and cardiovascular diseases (CVD). However, some points need to be clarified:

1. Could the authors present both groups of women with the WHO classification of symptoms (asymptomatic, mild-moderate, and severe infection).

2. Lack of information on the baseline and follow-up of CVD patients. Please provide how many years CVD before COVID-19 infection, treatment for CVD (yes or no) and type of treatment, lost of follow-up during COVID-19 infection, treatment delay during COVID-19 infection.

3. Please explain why the propensity score matching was used as the method for balancing weights.

Reviewer #3: The paper has major problems, denying it the right to be published. The main problems are (1) The large proportion of missing data of the patients’ background diseases, which can highly influence the results. (2) The lack of information on CVD definition. (3) The diagnosis method of COVID-19, which is clinically based and not confirmed by PCR in my understanding.

- English editing is required.

- Abstract: “cardiovascular diseases” definition required. Which diseases were included?

- Methods:

o “The case definition of SARS is of an individual with flu-like syndrome”- A confirming PCR test was not obligatory for diagnosis?

o Children were included (age 10-18), in my opinion this population deserves a sub-analysis.

o “To control selection biases in non-experimental studies, the CVD and non-CVD groups were balanced with respect to..”- “balanced” needs to be written “adjusted”.

- Results:

o “We selected only the confirmed and hospitalized cases of COVID-19”- The confirmation methods needs to be specified in details in the “Methods” section.

o 602 of 3,562 cases had CVD? It is a young population, so it seems to me to be over-estimated. Please, again, specify the definition of CVD in this study. Which ICD codes were included?

o “We noticed that the absolute numbers were increased in both groups from March to May 2020, with a high level until July.” – What absolute numbers?

o “This was different from what happened in the 2nd wave in which CVD patients were mostly affected.” – How did you conclude this? Did you calculate the proportion out of the entire “maternal” population (including non-COVID)?

o In table 1-

� What is included under “Hemopathy”? “Hepatopathy”? “Pneumopathy”? “Immunosuppression”? “Nephropathy”?

� How did you define obesity?

o What was the absolute mortality rate in every group?

- Conclusions- Most of the conclusions cannot be referred to without the above information. That is why, in fact, the paper is rejected.

- Limitation-

o “limitations of the study, we should consider that the completion of the notification system included information about the presence or absence of CVD in 39.58% of the notifications, with a high percentage of loss.” Can you clarify this sentence? Is approximately 60% of the patients’ background status missing?

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Reviewer #1: Yes: Charalampos S Siristatidis

Reviewer #2: No

Reviewer #3: No

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Cardiovascular diseases worsen the maternal prognosis of COVID-19

PONE-D-22-08926R1

Dear Dr. Luciana Graziela de Godoi,

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.

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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,

Vipa Thanachartwet, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

All issues were revised according to the reviewers' comments and suggestions.

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: (No Response)

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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 #1: (No Response)

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

Reviewer #1: (No Response)

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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: (No Response)

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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 #1: (No Response)

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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)

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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 #1: No

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