COVID-19 Not Hypertension or Diabetes Increases the Risk of Preeclampsia among a High-Risk Population

Round 1

Reviewer 1 Report

Comments for author File: Comments.pdf

Author Response

Overall, this is a clear, concise, and well-written manuscript demonstrating that COVID 19 infection during pregnancy increases the risk for preeclampsia in pregnant women with preexisting hypertension or Diabetes. The introduction is relevant, and theory based. Sufficient information about the previous study findings is presented for readers to follow the present study rationale and procedures. The methods are generally appropriate, and the results are clear and compelling. The authors make a systematic contribution to the research literature in this area of outcomes of pregnancies affected by COVID19. The prospective nature of the work, with COVID19 pregnancies, is a welcome addition. However, some specific concerns need to be addressed.

 

1) Table-1 and 2 should be presented like supplemental table with lines separating the columns and rows

Response. We thank the reviewer for this suggestion and have made the appropriate table revisions in the revised manuscript.

2) Several places in the manuscript, such as in line# 177, please replace “not a statistical difference “with “no statistical difference”

Response. We thank the reviewer for this comment and have made the suggested changes in the revised manuscript.

3) In line#212, add “for” after “the risk”

Response. We thank the reviewer for this comment and have made the suggested addition in the revised manuscript.

4) In line# 245, please add “of these “after 1-5% and replace “with” by ‘had”.

Response. We thank the reviewer for this comment and have made the suggested changes in the revised manuscript.

Author Response File: Author Response.docx

Reviewer 2 Report

In the present study, the authors report that COVID-19 infection increases the risk of preeclampsia and preterm delivery. This fact has already been reported and is not particularly new. Nevertheless, I appreciate that the present paper analyses the racial background of the patients and the attention paid to comorbidities such as obesity and essential hypertension.

However, there are several problems with this manuscript

1 Gestational hypertension is not a single disease; there is a group with early onset and poor prognosis and a group with late onset and mild prognosis. This paper categorises all into one patient group, which cannot be assessed. We want to assess whether the number of difficult-to-treat early―onset groups has increased.

 

2. The developmental pathology of gestational hypertension is important regarding placental villus invasion failure in early-onset and placental dysfunction in mid to late-onset, particularly villus degeneration and thrombus formation. I understand that COVID-19 infection is involved in the latter, but it may also have an effect on trophoblastic invasion in early pregnancy. Periodontal disease and chronic urinary tract infection affect early trophoblastic invasion (Hirohata et al J.Periodontoogy2017 https://doi.org/10.1902/jop.2017.170193) . In this context, the prognosis of pregnant women infected in early pregnancy should be investigated.

Author Response

In the present study, the authors report that COVID-19 infection increases the risk of preeclampsia and preterm delivery. This fact has already been reported and is not particularly new. Nevertheless, I appreciate that the present paper analyses the racial background of the patients and the attention paid to comorbidities such as obesity and essential hypertension.

However, there are several problems with this manuscript

 

1 Gestational hypertension is not a single disease; there is a group with early onset and poor prognosis and a group with late onset and mild prognosis. This paper categorises all into one patient group, which cannot be assessed. We want to assess whether the number of difficult-to-treat early―onset groups has increased.

Response. We appreciate the reviewer’s comments and whole heartedly agree that gestational hypertension itself is not a single disease. Our hospital practices utilize a variety of hypertensive disorders of pregnancies as defined by the American College of Obstetrics and Gynecology. Under this umbrella are gestational hypertension, chronic hypertension, preeclampsia, super-imposed preeclampsia, HELLP syndrome and eclampsia. We apologize if there is any confusion, however the current manuscript does not focus or highlight gestational hypertension, but instead focuses on the diagnosis and outcome of preeclampsia. As outlined in the methods for statistical purposes we did categorize women diagnosed with gestational or chronic hypertension together. In the revised manuscript we tried to increase the transparency of this by adding the number of women who had gestational hypertension instead of chronic hypertension for both the controls and cases (lines 171-173). Additionally, we added a sentence clarifying that pre-existing hypertension was a diagnosis of chronic or gestational hypertension at the time of admission (lines 189-190).

 

2. The developmental pathology of gestational hypertension is important regarding placental villus invasion failure in early-onset and placental dysfunction in mid to late-onset, particularly villus degeneration and thrombus formation. I understand that COVID-19 infection is involved in the latter, but it may also have an effect on trophoblastic invasion in early pregnancy. Periodontal disease and chronic urinary tract infection affect early trophoblastic invasion (Hirohata et al J.Periodontoogy2017 https://doi.org/10.1902/jop.2017.170193) . In this context, the prognosis of pregnant women infected in early pregnancy should be investigated.

Response. We thank the reviewer for their insight and we definitely do agree that the full affect of women infected early in pregnancy needs to be examined. As a matter of fact, we are currently performing laboratory analysis on placentas from women infected during the 1^st trimester and who contracted COVID immediately prior to conception to compare placental villous trophoblast invasion.  We have added a statement to our conclusion highlighting the importance of the placental investigations.

Reviewer 3 Report

I have reviewed the article “COVID-19 Not Hypertension or Diabetes Increases the Risk of 2 Preeclampsia among a High-Risk Population”.
The theme of the article is very important as the COVID 19 starts as a respiratory infection and usually ends as a vascular disease. There is a lot of literature showing that COVID 19 disease is influenced by Hypertension and preeclampsia and these two diseases are negatively influenced by COVIC 19.

The manuscript is clear and it evaluates a number of 100 patients in a region with important heterogeneity of the population concerning race/ethnicity, BMI, chronic hypertension and diabetes mellitus. The only comment is that the power of the statistics is limited to the relatively small number of the patients.

The design of the study is proper and the statistical analyze of the data is provided clear and comprehensive. The figures and the tables are expressive and the statistics is presented.

The conclusions are arising from the data and statistical analyze and are consistent with the evidence presented.

The bibliography is very new as the oldest article cited is from 2020.

The only comment is that the power of the statistics is limited to the relatively small number of the patients.

Author Response

I have reviewed the article “COVID-19 Not Hypertension or Diabetes Increases the Risk of 2 Preeclampsia among a High-Risk Population”.
The theme of the article is very important as the COVID 19 starts as a respiratory infection and usually ends as a vascular disease. There is a lot of literature showing that COVID 19 disease is influenced by Hypertension and preeclampsia and these two diseases are negatively influenced by COVIC 19.

The manuscript is clear and it evaluates a number of 100 patients in a region with important heterogeneity of the population concerning race/ethnicity, BMI, chronic hypertension and diabetes mellitus. The only comment is that the power of the statistics is limited to the relatively small number of the patients.

The design of the study is proper and the statistical analyze of the data is provided clear and comprehensive. The figures and the tables are expressive and the statistics is presented.

The conclusions are arising from the data and statistical analyze and are consistent with the evidence presented.

The bibliography is very new as the oldest article cited is from 2020.

The only comment is that the power of the statistics is limited to the relatively small number of the patients.

Response. We thank the reviewer for this comment. Our statistician for this study (Wondwosen Yimer) has calculated the power and we have included it in the revised manuscript. The power analysis found that the study was powered at 99% to explore the relationship between preeclampsia and COVID using diabetes or hypertension as a covariate in multiple logistic regression.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Thanks for your revision.