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Placenta. 2022 Jan;117:187-193. doi: 10.1016/j.placenta.2021.12.002. Epub 2021 Dec 02.

Placental SARS-CoV-2 distribution correlates with level of tissue oxygenation in COVID-19-associated necrotizing histiocytic intervillositis/perivillous fibrin deposition.

Placenta

Quanfu Mao, Sharon Chu, Svetlana Shapiro, Lawrence Young, Melissa Russo, Monique E De Paepe

Affiliations

  1. Department of Pathology, Women and Infants Hospital, and Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Providence, USA.
  2. Department of Maternal-Fetal Medicine, Women and Infants Hospital, and Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, USA.
  3. Department of Pathology, Women and Infants Hospital, and Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Providence, USA. Electronic address: [email protected].

PMID: 34929459 PMCID: PMC8638245 DOI: 10.1016/j.placenta.2021.12.002

Abstract

INTRODUCTION: Recent evidence supports the - rare - occurrence of vertical transplacental SARS-CoV-2 transmission. We previously determined that placental expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, and associated viral cell entry regulators is upregulated by hypoxia. In the present study, we utilized a clinically relevant model of SARS-CoV-2-associated chronic histiocytic intervillositis/massive perivillous fibrin deposition (CHIV/MPFVD) to test the hypothesis that placental hypoxia may facilitate placental SARS-CoV-2 infection.

METHODS: We performed a comparative immunohistochemical and/or RNAscope in-situ hybridization analysis of carbonic anhydrase IX (CAIX, hypoxia marker), ACE2 and SARS-CoV-2 expression in free-floating versus fibrin-encased chorionic villi in a 20-weeks' gestation placenta with SARS-CoV-2-associated CHIV/MPVFD.

RESULTS: The levels of CAIX and ACE2 immunoreactivity were significantly higher in trophoblastic cells of fibrin-encased villi than in those of free-floating villi, consistent with hypoxia-induced ACE2 upregulation. SARS-CoV-2 showed a similar preferential localization to trophoblastic cells of fibrin-encased villi.

DISCUSSION: The localization of SARS-CoV-2 to hypoxic, fibrin-encased villi in this placenta with CHIV/MPVFD suggests placental infection and, therefore, transplacental SARS-CoV-2 transmission may be promoted by hypoxic conditions, mediated by ACE2 and similar hypoxia-sensitive viral cell entry mechanisms. Understanding of a causative link between placental hypoxia and SARS-CoV-2 transmittability may potentially lead to the development of alternative strategies for prevention of intrauterine COVID-19 transmission.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Angiotensin-converting enzyme 2; Coronavirus; Hypoxia

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