key: cord-0766631-xng16e6u
authors: Vivanti, A. J.; De Luca, D.; Raschetti, R.; Benachi, A.
title: Obstetric and neonatal literature is complex and should be merged to understand perinatal SARS‐CoV‐2 infection
date: 2021-02-01
journal: Ultrasound Obstet Gynecol
DOI: 10.1002/uog.23582
sha: e0fb3dcc57e98abc581b3058bb0c06fe1ac1e5f4
doc_id: 766631
cord_uid: xng16e6u

Linked article: This Correspondence comments on Faure‐Bardon et al. Click here to view the article.

(1) Not all studied cases were tested for SARS-CoV-2 and the authors only assumed they were negative. (2) The authors refer to unique in-vivo human anatomical mapping across gestation of the distribution of the ACE2 receptor, although this has already been published 2 . Furthermore, in the reported cases, the fetuses carried significant brain malformations. The etiology or consequences of these anomalies may be responsible for deregulation of signaling cascades and thus modify the expression of many genes. It does not seem to us that these fetuses constitute the best models for the study of gene expression in the brain.

Moreover, brain ACE2 expression was not studied in the pediatric control patients. (3) It is not specified whether brain ACE2 expression was tested in all subjects. Their figure 2a shows the expression of ACE2 in several brain regions in a fetus at 20 + 1 weeks of gestation. However, fetal life is characterized by gene expression patterns that change over time. Certain genes are expressed in the first weeks of embryonic life and are then repressed, and vice versa 3 . For instance, placental ACE2 expression peaks near full term 2 . In addition, it is known that the brain develops rapidly at the end of the second trimester of pregnancy. The choice to analyze the expression of a protein in the brain after 20 weeks of gestation seems debatable. In addition, a systematic review of neonatal cases of SARS-CoV-2 infection 6 has shown that 20% of neonates with infection (congenital, intrapartum or neonatal) have neurological symptoms. The absence of ACE2 expression in the brain does not rule out the development of neurological manifestations, since the latter are due to endothelial cell damage and induced vascular inflammation, as seen in adult patients 7 . Our magnetic resonance imaging findings 4 are fully consistent with this pathogenetic pathway and similar to brain imaging findings in critically ill adult patients.

While we agree with Faure-Bardon et al. 1 that the literature published hitherto suggests that fetal malformations as a result of SARS-CoV-2 infection are unlikely, we feel that it is too early to assume that fetal and neonatal infections have no consequences, and believe that maternal and fetal protection should be the rule. 

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