Vertical Transmission of SARS-CoV-2 Infection and Miscarriage in the Second Trimester: Report of an Immunohistochemically Proven Case

Round 1

Reviewer 1 Report

In this article, the authors present the case of a pregnant woman with SARS-CoV 2 infection in whom, after infection, gestation culminated in a previable delivery. Subsequent study was able to identify unequivocal signs of SARS-CoV 2 infection in the fetus. 

I find the article interesting, as it adds to the body of evidence in this regard. However, I believe that there are some questions that should be resolved before it can be accepted.

1. Why was it not ruled out that the patient could have a co-infection by another germ during or after the acute event of SARS-CoV 2 infection? I consider this aspect relevant, as it could affect the interpretation of the histopathological findings. The clinic experienced by the patient is compatible with acute chorioamnionitis (abdominal pain, contractions), and therefore infection by other more frequent germs has to be ruled out by blood culture, urine culture and culture of placental or fetal aspirate before assuming that the clinic is linked to an acute event one week earlier, despite finding SARS-CoV 2 nucleocapsid proteins in the fetus, which demonstrates vertical transmission but does not necessarily link the infection to the event.

2. In the discussion (lines 213 and 214), the authors comment the following: "In the studied pregnant patient, the observed morphological characteristics of the placenta and amniochorionic membranes clearly indicating inflammatory process are the most likely cause of the ensuing miscarriage". Perhaps it would be better to say that they were the cause of the precipitated delivery at a predictable stage of gestation, since intrauterine death did not occur. 

3. In line 222 they state the following: "It is conceivable that this might cause subsequent malformations". The possibility of malformations depends on the time of gestation, being already improbable from week 10 concerning the central nervous system after infection by SARS-CoV 2, since, although there is vertical transmission, it is unlikely that it is a virus as teratogenic and neurotropic as Zika. Therefore, I invite you to modify the sentence, expressing the probability of the appearance of neurodevelopmental alterations after birth, instead of malformations, or merging it with the last paragraph of the discussion, where this possibility is already reflected.

4. It is difficult to extrapolate from your clinical case the following conclusion: "It is possible that vertical transmission of COVID-19 could have detrimental impact on crucial processes like cells proliferation, migration and maturation underlying the development of vital organs - brain and spinal cord, lungs etc." In my opinion, neither your clinical case nor the existing literature allows to support this conclusion, so I would recommend you to rewrite the sentence, simply assuming a vertical transmission at the level of CNS and other organs, whose impact should be evaluated in future studies.

5. I recommend a revision of the English, especially in the exposition of the clinical case.

In conclusion, I consider that the authors present an interesting and detailed case, however it is necessary to resolve these issues before publication.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

I am pleased to say that this work is significant and I recommend to accept publication in this present form.

Author Response

The authors would like to thank Reviewer 2 for the positive feedback!