Coronavirus Disease 2019 and the Placenta: A Literature Review

Overview

Journal Placenta

Publisher Elsevier

Specialties Gynecology & Obstetrics
Physiology
Reproductive Medicine

Date 2022 Jul 25

PMID 35872511

Authors

Samwel R Gesaka

Moses M Obimbo

Anthony Wanyoro

Affiliations

Soon will be listed here.

Abstract

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of multiple organs and organ systems. Due to the novelty of the disease, there is a need to review emerging literature to understand the profile of SARS-CoV-2 in the placenta. This review sought to evaluate the literature on the mediators, mechanism of entry, pathogenesis, detection, and pathology of SARS-CoV-2 in the placenta. Systematic literature searches found 96 eligible studies. Our review revealed that SARS-CoV-2 canonical mediators, angiotensin-converting enzyme-2 (ACE2), and transmembrane serine protease-2 (TMPRSS2) are variably expressed in various placenta compartments, including the villous cytotrophoblasts, syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs) throughout pregnancy. Placental SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs), including basigin (BSG/CD147), dipeptidyl peptidase-4 (DPP4/CD26), cathepsin B/L (CTL B/L), furin, interferon-induced transmembrane protein (IFITM1-3), and lymphocyte antigen 6E (LY6E) may increase or reduce the permissiveness of the placenta to SARS-CoV-2. EVTs express genes that code for proteins that may drive viral pathogenesis in the placenta. Viral RNA, proteins, and particles were detected primarily in the STBs by in situ hybridization, immunohistochemistry, electron microscopy, and polymerase chain reaction. Placental pathology in SARS-CoV-2-infected placentas included maternal and fetal vascular malperfusion and a generally nonspecific inflammatory-immune response. The localization of SARS-CoV-2 receptors, proteases, and genes involved in coding proteins that drive viral pathogenesis in the placenta predisposes the placenta to SARS-CoV-2 infection variably in all pregnancy trimesters, with antecedent placental pathology. There is a need for further studies to explicate the mechanism of entry and pathogenesis of SARS-CoV-2 in the placenta.

Citing Articles

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References

Roland M, Friis C, Voldner N, Godang K, Bollerslev J, Haugen G . Fetal growth versus birthweight: the role of placenta versus other determinants. PLoS One. 2012; 7(6):e39324. PMC: 3377679. DOI: 10.1371/journal.pone.0039324. View

Varghese P, Tsolaki A, Yasmin H, Shastri A, Ferluga J, Vatish M . Host-pathogen interaction in COVID-19: Pathogenesis, potential therapeutics and vaccination strategies. Immunobiology. 2020; 225(6):152008. PMC: 7434692. DOI: 10.1016/j.imbio.2020.152008. View

Leon-Juarez M, Martinez-Castillo M, Gonzalez-Garcia L, Helguera-Repetto A, Zaga-Clavellina V, Garcia-Cordero J . Cellular and molecular mechanisms of viral infection in the human placenta. Pathog Dis. 2017; 75(7). PMC: 7108519. DOI: 10.1093/femspd/ftx093. View

Facchetti F, Bugatti M, Drera E, Tripodo C, Sartori E, Cancila V . SARS-CoV2 vertical transmission with adverse effects on the newborn revealed through integrated immunohistochemical, electron microscopy and molecular analyses of Placenta. EBioMedicine. 2020; 59:102951. PMC: 7430280. DOI: 10.1016/j.ebiom.2020.102951. View

Sanchez J, Vigil-De Gracia P, Guerrero E, Gaitan M, Fu C, Chen-German M . Severe acute respiratory syndrome coronavirus 2 detected in placentas of 2 coronavirus disease 2019-positive asymptomatic pregnant women-case report. AJOG Glob Rep. 2021; 1(1):100001. PMC: 7838577. DOI: 10.1016/j.xagr.2020.100001. View

Li M, Chen L, Zhang J, Xiong C, Li X . The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLoS One. 2020; 15(4):e0230295. PMC: 7161957. DOI: 10.1371/journal.pone.0230295. View

Lyden T, Anderson C, Robinson J . The endothelium but not the syncytiotrophoblast of human placenta expresses caveolae. Placenta. 2002; 23(8-9):640-52. DOI: 10.1053/plac.2002.0847. View

Wang Y, Wang Y, Luo W, Huang L, Xiao J, Li F . A comprehensive investigation of the mRNA and protein level of ACE2, the putative receptor of SARS-CoV-2, in human tissues and blood cells. Int J Med Sci. 2020; 17(11):1522-1531. PMC: 7359402. DOI: 10.7150/ijms.46695. View

Flores-Pliego A, Miranda J, Vega-Torreblanca S, Valdespino-Vazquez Y, Helguera-Repetto C, Espejel-Nunez A . Molecular Insights into the Thrombotic and Microvascular Injury in Placental Endothelium of Women with Mild or Severe COVID-19. Cells. 2021; 10(2). PMC: 7916402. DOI: 10.3390/cells10020364. View

10.

Fuentes-Prior P . Priming of SARS-CoV-2 S protein by several membrane-bound serine proteinases could explain enhanced viral infectivity and systemic COVID-19 infection. J Biol Chem. 2020; 296:100135. PMC: 7834812. DOI: 10.1074/jbc.REV120.015980. View

11.

Adhikari E, Moreno W, Zofkie A, MacDonald L, Mcintire D, Collins R . Pregnancy Outcomes Among Women With and Without Severe Acute Respiratory Syndrome Coronavirus 2 Infection. JAMA Netw Open. 2020; 3(11):e2029256. PMC: 7677755. DOI: 10.1001/jamanetworkopen.2020.29256. View

12.

Mongula J, Frenken M, van Lijnschoten G, Arents N, de Wit-Zuurendonk L, Schimmel-de Kok A . COVID-19 during pregnancy: non-reassuring fetal heart rate, placental pathology and coagulopathy. Ultrasound Obstet Gynecol. 2020; 56(5):773-776. PMC: 7461013. DOI: 10.1002/uog.22189. View

13.

Karimi-Zarchi M, Neamatzadeh H, Dastgheib S, Abbasi H, Reza Mirjalili S, Behforouz A . Vertical Transmission of Coronavirus Disease 19 (COVID-19) from Infected Pregnant Mothers to Neonates: A Review. Fetal Pediatr Pathol. 2020; 39(3):246-250. PMC: 7157948. DOI: 10.1080/15513815.2020.1747120. View

14.

Schwartz D, Baldewijns M, Benachi A, Bugatti M, Collins R, De Luca D . Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).... Arch Pathol Lab Med. 2021; 145(5):517-528. DOI: 10.5858/arpa.2020-0771-SA. View

15.

Hecht J, Quade B, Deshpande V, Mino-Kenudson M, Ting D, Desai N . SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers. Mod Pathol. 2020; 33(11):2092-2103. PMC: 7395938. DOI: 10.1038/s41379-020-0639-4. View

16.

Edlow A, Li J, Collier A, Atyeo C, James K, Boatin A . Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020; 3(12):e2030455. PMC: 7756241. DOI: 10.1001/jamanetworkopen.2020.30455. View

17.

Suhren J, Meinardus A, Hussein K, Schaumann N . Meta-analysis on COVID-19-pregnancy-related placental pathologies shows no specific pattern. Placenta. 2021; 117:72-77. PMC: 8525005. DOI: 10.1016/j.placenta.2021.10.010. View

18.

Simoes E Silva A, Leal C . Is SARS-CoV-2 Vertically Transmitted?. Front Pediatr. 2020; 8:276. PMC: 7243472. DOI: 10.3389/fped.2020.00276. View

19.

Baergen R, Heller D . Placental Pathology in Covid-19 Positive Mothers: Preliminary Findings. Pediatr Dev Pathol. 2020; 23(3):177-180. PMC: 7252218. DOI: 10.1177/1093526620925569. View

20.

Harapan H, Itoh N, Yufika A, Winardi W, Keam S, Te H . Coronavirus disease 2019 (COVID-19): A literature review. J Infect Public Health. 2020; 13(5):667-673. PMC: 7142680. DOI: 10.1016/j.jiph.2020.03.019. View