Peer review of: Transplacental transmission of SARS-CoV-2 infection (2020)

REVIEWER COMMENTS 

 

Reviewer #1 (Remarks to the Author): 

 

Vivanti et al. report transplacental transmission of SARS-CoV-2 infection. Viral RNA was detected in 
placenta, amniotic fluid, and baby blood. Since detection of the virus is the key to the conclusion, the 
authors should add results on virus isolation from these tissues. In addition, immunostaining of 
these tissues/cells with viral proteins will also support the conclusion. 

Minor point: 

Figures 2 and 4: arrows should be added to the figures, as indicated in the legends. 

 

 

 

Reviewer #2 (Remarks to the Author): 

 

Thank you for asking me to review this manuscript. There are some interesting findings which are 
unique; however, overall tone needs to be deemphasized to indicate “probable” congenital infection 
unless the following items are clarified further. Additionally, neurological findings need to be 
reported as an association for now. 

 

Abstract: 

 

1. Would suggest removing claims of “first time” from manuscript as there are other cases reported 
in literature and more reports are forthcoming. 

 

Introduction: 

1. First paragraph – again remove claims of “first time”. 

2. What is category III fetal tracing and what is category II cesarean section – please clarify. 

3. Was the cesarean section performed due to maternal cough? It says maternal respiratory status 
but not indicated what was her status from respiratory perspectives? 

4. What was the reason for maternal admission for 6 days after delivery? 

5. What was the reason for Apgar score going down from 4 to 2 if resuscitation was performed 
according to guidelines? 

6. What were the reasons for POC echo and lung ultrasound examination? 

7. What is the results of CSF RT PCR? What is detailed CSF report? 

8. What is meant by placenta was extremely positive – was it swabs? Was it maternal side or fetal 
side? 

9. How do authors explain signs of chronic intervillositis? If mother was infected only 5 days prior to 
birth? 

10. What was trophoblastic involvement? 

11. Was viral gene isolated from placental tissues? 

Discussion: 

1. Remove “first”. 

2. There is a report of presence of viral genes in amniotic fluid, so this needs to be corrected. 
https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1002/pd.5713. 

3. I would refrain from using term “vertical” or “Horizontal” as it should be more or less mechanism 
based rather than direction based. 

4. BAL methods reference is author’s own paper where the method is not the investigation target. 
(reference 3 in online methods). 

5. Before confirming the case as “confirmed” case there are several clarifications needed to be 
fulfilled 

a. What is the false positive test rate of this testing? Above cycle threshold of 30, what is the false 
positive rate? 

b. Crushed sample of placenta – suggest possibility of contamination by maternal blood – how can 
this be differentiated? 

c. Newborn blood and maternal vaginal swab has very high cycle threshold (to the level which could 
be considered even negative) – please elaborate more. 

d. Figure 3 has 3 Newborn NP swabs – which one is on which day? 

e. Confirmed case would require clinical features of infection as well – for which clinical phenotype is 
still unknown and what neurological findings baby had could be an association with possible birth 
asphyxia picture (low Apgar, need for resuscitation, need for respiratory support) etc. 

6. Emphasis is given on transplacental transmission – which indicate that it look like peripartum 
transmission. Is this what authors intend to say? 

7. Before neurological findings are ascribed to possibility of association with SARS-CoV-2 further 
information is needed 

a. What was baby’s first blood gas and what recovery occurred in blood gas over time? 

b. What was baby’s first blood count? 

c. What was baby’s clinical neurological examination at birth and immediately thereafter? 

d. What sedation/muscle relaxants baby received on first day? 

e. Were virological studies conducted on CSF sample? 

f. Please provide full CSF report for better interpretation. 

8. Figure 4, panel A – arrow is not seen and how is it possible to see fibrin deposition 
macroscopically? 

9. The placental histopathology revealed chronic histiocytic intervillositis, which is a chronic 
immunologic disorder associated with intrauterine growth retardation and miscarriage or stillbirth. 
How authors thinks it is associated with congenital infections especially viral infection. Where are 
the histiocytes located? Around the chorionic villi or elsewhere? 

10. The significance of the cycle threshold (Ct) results for the PCR tests performed on the mother 
and child is not explained in the manuscript. First of all, for clinicians, it would be important to 
explain the inverse relationship of Ct number to viral load. 

11. It will be useful in appendix to have table of investigations with cycle threshold values and an 
explanation that the viral loads (as estimated from Ct values) were correlate to ……etc. 

12. Reference 16 is suggested for diagnosis of SARS-CoV-2 in neonates from China. Authors mention 
that their study meets this definition. Could you please clarify further. The paper indicates that baby 
should meet all four criteria; one of which includes “chest radiographs showing abnormalities, 
including unilateral or bilateral milled glass opacities”. Please report any chest x-ray findings after 
intubation or soften that conclusion. 

13. In the absence of any other organ involvement, too much emphasis is placed on MRI findings. 
This needs to be softened to an association. 

14. What is inherent reliability of testing as indicated by manufacturer and field testing for this 
particular test and it need to be reported. 

15. What treatment did baby receive? Did baby receive any antivirals? 

16. What follow up data are available for baby and mother? 

17. Would authors suggest change in timeline for testing of newborns born to mother who is SARS-
CoV-2 positive, which currently is around 24 hours of age? based on their findings? 

 

General comment: 

1. Change all reference to isolation of “SARS-CoV-2 gene target isolation” by RT-PCR and not “virus 
isolation”. 

2. Figure 1 – does not add much to paper and can be removed. 

3. Table of laboratory findings may be more useful.