Assessing the Impact of COVID-19 on Pregnancy and Maternal Outcomes: A Slovak National Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study encompasses over 3 years from March 2020 to May 5, 2023. During this period of the COVID-19 pandemic, SARS-CoV-2 evolved with high mutation rate, leading to abundant variations within its genome. Over 150,000 types of mutations have been detected in the SARS-CoV-2 genome and over 1600 lineages (variants) have emerged, including the Variants of Concern: Alpha, Delta and Omicron, etc. Notably, viral virulence varies significantly from variant to variant. The relationship between viral variants, virulence, and disease severity is not addressed/discussed in this study.

As discussed in lines 405 to 413, please include retrospective data directly from Slovak hospitals. For the critically ill or deceased COVID-19-positive women, please indicate the time and variant type, if known. If not known, please indicate the variant circulating in the area at that time.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors The authors designed an epidemiological study on the impact SARS-CoV-2 infection might have had on pregnant women. However, we believe it is important to clarify some methodological aspects

How was the sars-cov-2 infection diagnosed? What type of test was used? What were the respiratory symptoms? What was the prevalence of respiratory failure? Have parameters indicative of respiratory function been assessed? (oxygen saturation, PO2/FiO2?) Since 30% required invasive ventilatory support, the evaluation of respiratory function should be better described. Has an ultrasound examination of the lungs been done? Have there been diagnoses of infections included in the torch complex? also considering the small number of patients, a different and more in-depth statistical analysis would be necessary to evaluate the impact of the SARS-CoV2 infection. Equally important would have been to have a control group

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

 The study is a national observational descriptive study of SARS-CoV-2 positive cases among pregnant women and on pregnancy outcomes.

 There is a major issue in this article. Data from the same patient cohort are presented from three different sources (self-reported, prenatal care, and labor ward), and the data are inconsistent with each other. Additionally, the same topics (such as complications or comorbidities) are reported multiple times with significantly different results. According to the authors, the latter two data collections are still ongoing. In my opinion, the article is not publishable in its current form, and I suggest two possible solutions: 1) limit the analysis to the data from the self-reported questionnaires and redefine the article’s objectives, or 2) complete data collection from the other two sources and present all data only once

I am adding below a series of suggestions that I hope will help the authors in drafting the new version of their article

 Lines 48-49: The way it’s presented, the phrase 'many of these studies were conducted outside of Europe, were hospital-based, or involved only a limited number of severe cases' seems like a list of limitations of the studies described. Perhaps the limited number of severe cases could be due to the low frequency of severe cases, but why would being hospital-based be considered a limitation? Would one expect studies on pregnancy and childbirth in COVID-19 patients to gather a large number of patients in a 'non-hospital-based' setting?

 

Lines 67-69: Further analysis is ongoing, including symptom severity in its relation to pre-existing conditions/ comorbidities of affected women, and treatment approaches. Is this analysis included or beyond the manuscript? Why is defined as “ongoing”?

Lines 97-102 and 107-112: “Prenatal Care Questionnaire” and “Hospitalization Questionnaire “ are ongoing. It is rather unusual in a paper to reference a part of the study that is still ongoing. I therefore ask the authors to either remove any reference to this phase of the study or to wait until it is complete and include the results in this manuscript

 

Line 129: the mean gestational age at infection was 23 weeks and 2 days. What do you mean by 'at infection'? Do you mean the day the infection was contracted (how would this be identified?), the day the COVID test was taken, or the day the positive result was provided? Given the difficulties in carrying out tests in the early stages of the pandemic, I believe it would be helpful to provide more details on the definition of 'at infection.'

There is a formatting issue with Table 1; characters often change between tables and text

Line 150: only 1 % of women reporting an asymptomatic course. In Table 2: Asymptomatic         N=15   %=6,25. Please resolve the discrepancy

Line 170: why are hematological or gastrointestinal complications considered as obstetric complications?

Table 3: There may be a bias in evaluating complications that occurred before and after SARS-CoV-2 infection, as we cannot definitively state that complications arising after the infection are directly attributable to it. To aid in data interpretation (also considering that pregnancies have progressed and the complication rate may naturally change), it could be helpful to organize the table to show, for each complication, the frequency before and after infection. In fact, a more accurate analysis might come from comparing post-infection data with those of uninfected patients at a comparable gestational period

 The table title should be on top of the table itself, the same for table 6

 Line 141: 5 delivered preterm, likely as a result of the infection. On the basis of which data authors suggest a correlation between preterm delivery and covid infection? Is the rate of covid infected women delivering preterm significantly higher than that of the non-infected population?

 Line 186: Why are included in the study 56 women vaccinated post-pregnancy? The vaccination data are somewhat confusing. I would suggest excluding women who were vaccinated after pregnancy; however, it would be more interesting to know, for example, whether those vaccinated before or during pregnancy experienced different obstetric complications compared to the unvaccinated population or had a different rate of hospitalization, if the type of delivery differed, if the newborn's COVID status at birth was different, and other developments that are more relevant and interesting to the study's topic

 Lines 206-210. How were these data collected? This is too general as a sentence to be included in a scientific manuscript

 Lines 217-219: Most were married (80 %), employed (88 %), and well-educated, with 70 % holding university degrees and 30 % being high school graduates. Are the data about marriage and education useful to the aim of the study? If yes please explain. The same for lines 261-262, by the way the data change despite talking about the same population…

 Lines 221-223: There is already a section dedicated to symptomatology earlier in the article. I find it not useful, and even confusing, to revisit the same topic by presenting different data on a smaller population, based on data from other sources regarding the same patients. I don’t understand the purpose of this repetition of symptomatology. Are you perhaps trying to find a correspondence between what patients reported and what their healthcare providers stated? This is far from the aim of this study, as declared at the beginning of the manuscript. The same for lines 244-251

 Line 226: the primary abnormality was an increase in CRP levels. an increase in CRP levels is not an abnormality in case of a viral infection Melbye H, Hvidsten D, Holm A, Nordbø SA, Brox J. The course of C-reactive protein response in untreated upper respiratory tract infection. Br J Gen Pract. 2004 Sep;54(506):653-8. PMID: 15353049; PMCID: PMC1326064.

 Lines 219-220: the participants had no significant comorbidities. Table 8: Comorbidity n=21, %=39,62

 Discussion. Lines 292-297 I do not consider it appropriate to make this type of comparison. We know well that patient hospitalization policies during the pandemic period were not the same across all countries affected by the pandemic, and that patients with the same symptoms might have been hospitalized in one country but not in another, depending on bed availability, admission criteria, and many other factors beyond the scope of this work. For this reason, we cannot state that 'Slovakia has shown a potentially higher hospitalization rate since 13 out of 240 (5.42%) pregnant women who tested positive required hospitalization. Perhaps Slovakia had greater bed availability, better organization, or a different policy regarding pregnant women, which led to a higher number of hospitalizations.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors although with some limitations due to the retrospective nature of the study, the authors answered the questions posed

Author Response

Dear Reviewer,

Thank you for taking the time to review my manuscript and providing valuable feedback. Your insights have been invaluable in refining the manuscript, and I hope the revised version meets your expectations and contributes meaningfully to the discussion on this important topic.

Thank you once again for your time and expertise.

Best regards,
Dr. Adriána Goldbergerová

Reviewer 3 Report

Comments and Suggestions for Authors

The authors have addressed all the comments I raised, and I now consider their work suitable for publication.

Author Response

Dear Reviewer,

Thank you for taking the time to review my manuscript and for providing such valuable feedback. Your insights have been instrumental in refining the work. I truly appreciate your time and expertise.

Best regards,
Dr. Adriána Goldbergerová