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
Affiliations
- Department of Pathology, Women and Infants Hospital, and Department of Pathology and Laboratory Medicine, Alpert Medical School of Brown University, Providence, USA.
- Department of Maternal-Fetal Medicine, Women and Infants Hospital, and Department of Obstetrics and Gynecology, Alpert Medical School of Brown University, Providence, USA.
- 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
References
- Eur Heart J. 2005 Feb;26(4):369-75; discussion 322-4 - PubMed
- Arch Pathol Lab Med. 2021 May 1;145(5):517-528 - PubMed
- Fetal Pediatr Pathol. 2012 Dec;31(6):394-400 - PubMed
- Placenta. 2016 Jan;37:1-6 - PubMed
- Am J Perinatol. 2020 Jun;37(8):861-865 - PubMed
- Rev Bras Ginecol Obstet. 2021 Mar;43(3):207-215 - PubMed
- Pediatr Pathol Lab Med. 1996 Nov-Dec;16(6):901-7 - PubMed
- Cell. 2020 Apr 16;181(2):271-280.e8 - PubMed
- Pediatr Infect Dis J. 2020 Sep;39(9):e257-e260 - PubMed
- Placenta. 2020 Jan 15;90:9-17 - PubMed
- Lancet. 2020 Feb 22;395(10224):565-574 - PubMed
- N Engl J Med. 2003 May 15;348(20):1953-66 - PubMed
- Pediatr Dev Pathol. 2015 Sep-Oct;18(5):380-6 - PubMed
- JCI Insight. 2020 Jun 18;5(12): - PubMed
- J Med Virol. 2020 Jun;92(6):595-601 - PubMed
- N Engl J Med. 2020 Feb 20;382(8):727-733 - PubMed
- Prenat Diagn. 2020 Dec;40(13):1759-1761 - PubMed
- Placenta. 2021 Jan 15;104:261-266 - PubMed
- Cell. 2020 Apr 16;181(2):281-292.e6 - PubMed
- N Engl J Med. 2012 Nov 8;367(19):1814-20 - PubMed
- Nature. 2003 Nov 27;426(6965):450-4 - PubMed
- Arch Pathol Lab Med. 2020 Dec 1;144(12):1451-1456 - PubMed
- Clin Sci (Lond). 2014 Apr;126(7):507-16 - PubMed
- Eur J Clin Microbiol Infect Dis. 2020 Dec;39(12):2441-2445 - PubMed
- Am J Surg Pathol. 1998 Aug;22(8):1006-11 - PubMed
- Nat Commun. 2020 Jul 14;11(1):3572 - PubMed
- Cancer Discov. 2020 Jun;10(6):779-782 - PubMed
- J Med Virol. 2021 Feb;93(2):1038-1044 - PubMed
- Placenta. 2020 Oct;100:69-74 - PubMed
- Am J Obstet Gynecol MFM. 2020 Aug;2(3):100145 - PubMed
- CMAJ. 2020 Jun 15;192(24):E647-E650 - PubMed
- Eur J Pharmacol. 2016 Mar 5;774:25-33 - PubMed
- J Cell Physiol. 2019 Nov;234(11):20420-20431 - PubMed
- Lab Invest. 2020 Nov;100(11):1485-1489 - PubMed
- Pediatr Infect Dis J. 2020 Sep;39(9):e265-e267 - PubMed
- Lancet. 2020 Feb 15;395(10223):497-506 - PubMed
- JAMA Pediatr. 2020 Jul 1;174(7):722-725 - PubMed
- Hum Pathol. 2021 Mar;109:69-79 - PubMed
- Am J Obstet Gynecol MFM. 2020 Nov;2(4):100197 - PubMed
- Oncogene. 2010 Dec 16;29(50):6509-21 - PubMed
- Lancet. 2020 Feb 15;395(10223):507-513 - PubMed
- Nat Med. 2020 May;26(5):681-687 - PubMed
- Cancer Res. 2000 Dec 15;60(24):7075-83 - PubMed
- Placenta. 2021 Feb;105:7-13 - PubMed
Publication Types