Anatomical and timely assessment of protein expression of angiotensin‐converting enzyme 2, SARS‐CoV‐2 specific receptor, in fetal and placental tissues: new insight for perinatal counseling

Infection with SARS‐CoV2 does not spare pregnant women and the possibility of vertical transmission which might lead to fetal damages is pending. Objective We hypothesized that the observed low incidence of perinatal infection could be related to a low expression of the membrane receptor for SARS‐CoV2, ACE2, in the fetal‐placental unit. We evaluated protein expression of ACE2 both in placentas and fetal organs from non‐infected pregnancies across gestation. Methods Discovery study. Immunocytochemistry analysis for ACE2 in organs and placentas were performed in May 2020, in samples from a registered biobank. Five cases of medical termination of pregnancy performed at between 15 and 38 weeks’ in healthy women. Paraffin‐embedded tissues (kidneys, brain, lungs, intestinal tract, heart). Matching tissues from 8‐year‐old children (N=4) were tested as controls. Seven placentas including those of the 5 cases, 1 of a 7‐week miscarriage and 1 of a symptomatic SARS‐COV2 pregnancy at 34 weeks. Tissues’ sections were incubated with rabbit monoclonal anti‐ACE2. Protein expression of ACE2 was detected by immunochemistry. Results ACE2 expression was detected in fetal kidneys, rectum and ileum across gestation and similarly in the pediatric control. It was barely detectable in lungs at 15 weeks’ and not found thereafter. In the pediatric control, ACE2 was only detectable in type 2 pneumocytes. No ACE2 expression was found in the cerebral ependymal, parenchyma nor in cardiac tissues ACE2 was expressed in syncitiotrophoblast and cytotrophoblast from 7th weeks’ onwards and across gestation but not in the amnion. Similar intensity and distribution of ACE2 staining were identified in the mother's SARS‐CoV2 placenta. Conclusions Marked placental expression of ACE2 provides a rationale for vertical transmission at cellular level. Absence of ACE2 expression in the fetal brain and heart is reassuring on the risk of congenital malformation. Clinical follow‐up of infected pregnant women and their children are needed to validate these observations. This article is protected by copyright. All rights reserved.