SARS-CoV-2 Infection and Placental Pathology Infecção por SARS-CoV-2 e patologia placentária

Leal, Caio Ribeiro Vieira; Maciel, Rayra Amana Macêdo; Corrêa Júnior, Mário Dias

doi:10.1055/s-0041-1730291

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Revista Brasileira de Ginecologia e Obstetrícia

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Review Article • Rev. Bras. Ginecol. Obstet. 43 (06) • June 2021 • https://doi.org/10.1055/s-0041-1730291 copy

SARS-CoV-2 Infection and Placental Pathology Infecção por SARS-CoV-2 e patologia placentária

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Placental pathophysiology in SARS-CoV-2 infection can help researchers understand more about the infection and its impact on thematernal/neonatal outcomes. This brief review provides an overview about some aspects of the placental pathology in SARSCoV- 2 infection. In total, 11 papers were included. The current literature suggests that there are no specific histopathological characteristics in the placenta related to SARSCoV- 2 infection, but placentas frominfected women aremore likely to show findings of maternal and/or fetal malperfusion. The most common findings in placentas from infected women were fibrin deposition and intense recruitment of inflammatory infiltrates. The transplacental transmission of this virus is unlikely to occur, probably due to low expression of the receptor for SARS-CoV-2 in placental cell types. Further studies are needed to improve our knowledge about the interaction between the virus and the mother-fetus dyad and the impact on maternal and neonatal/fetal outcomes.

Keywords:
SARS-CoV-2; Covid-19; pregnancy; placenta; pathology

Authors	Study characteristics	Main findings
Vivanti et al.¹⁰10 Vivanti AJ, Vauloup-Fellous C, Prevot S, Zupan V, Suffee C, Cao JD, et al. Transplacental transmission of SARS-CoV-2 infection. Nat Commun. 2020;11(01):3572. Doi: 10.1038/s41467-020-17436-6 https://doi.org/10.1038/s41467-020-17436...	Case report of transplacental transmission of SARS-CoV-2 in a pregnant woman in the third trimester	The first case of proven transplacental transmission of SARS-CoV-2. The RT-PCR was positive for SARS-CoV-2 genes on the placenta, amniotic fluid and maternal, and fetal blood. Placental histological examination revealed diffuse perivillous fibrin deposition with infarction and acute and chronic intervillositis.
Hosier et al.¹³13 Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, et al. SARS-CoV-2 infection of the placenta. J Clin Invest. 2020;130(09):4947-4953. Doi: 10.1172/JCI139569 https://doi.org/10.1172/JCI139569...	Case report of second trimester SARS-CoV-2-infected pregnancy complicated by severe preeclampsia and placental abruption	Placental histological examination showed diffuse perivillous fibrin deposition and an inflammatory infiltrate consistent with histiocytic intervillositis. There were no features of decidual vasculopathy. Placenta and umbilical cord tested positive for SARS-COV-2 RNA. Virus proteins were localized predominantly in the syncytiotrophoblast cells.
Hsu et al.¹⁴14 Hsu AL, Guan M, Johannesen E, Stephens AJ, Khaleel N, Kagan N, et al. Placental SARS-CoV-2 in a pregnant woman with mild COVID-19 disease. J Med Virol. 2021;93(02):1038-1044. Doi: 10.1002/jmv.26386 https://doi.org/10.1002/jmv.26386...	Case report of third trimester SARS-CoV-2-infected pregnant woman	Placental histological examination showed signs of maternal vascular malperfusion with hypertrophic arteriolopathy, but no fetal vascular malperfusion. There were signs of acute uterine hypoxia (subchorionic laminar necrosis) superimposed on chronic uterine hypoxia (extravillous trophoblasts and focal chronic villitis). Virus proteins were identified in chorionic villi endothelial cells and in trophoblasts.
Hecht et al.¹⁵15 Hecht JL, Quade B, Deshpande V, Mino-Kenudson M, Ting DT, Desai N, et al. SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas fromCOVID-19-positive mothers. Mod Pathol. 2020;33 (11):2092-2103. Doi: 10.1038/s41379-020-0639-4 https://doi.org/10.1038/s41379-020-0639-...	Case series and comparative study between 19 SARS-CoV-2 infected pregnant women and 3 sets of controls	There was no specific gross or characteristic histopathology present in the placentas, including the only two infected placentas.
Smithgall et al.¹⁶16 Smithgall MC, Liu-Jarin X, Hamele-Bena D, Cimic A, Mourad M, Debelenko L, Chen X. Third-trimester placentas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive women: histomorphology, including viral immunohistochemistry and in-situ hybridization. Histopathology. 2020;77(06): 994-999. Doi: 10.1111/his.14215 https://doi.org/10.1111/his.14215...	Case series and comparative study between 51 SARS-CoV-2-infected pregnant women and 25 SARS-CoV-2-negative pregnant women	There were no specific histopathological characteristics in the placentas related to SARS-CoV-2 infection. None of the placentas tested positive for SARS-CoV-2. Maternal/fetal vascular malperfusion was identified in infected women, and their placentas showed more villous agglutination and subchorionic thrombi compared with non-infected women.
Facchetti et al.¹⁷17 Facchetti F, BugattiM, Drera E, Tripodo C, Sartori E, Cancila V, et al. SARS-CoV2 vertical transmission with adverse effects on the newborn revealed through integrated immunohistochemical, electron microscopy and molecular analyses of Placenta. EBio- Medicine. 2020;59:102951. Doi: 10.1016/j.ebiom.2020.102951 https://doi.org/10.1016/j.ebiom.2020.102...	Case series of 15 SARS-CoV-2-infected pregnant women	Only 1 of the 15 placentas tested positive for SARS-CoV-2 genes. The comparison between this placenta and the other 14 showed no significant morphological differences, except for the prominent intervillous inflammation (showing variable changes compatible with fetal vascular malperfusion).
Ferraiolo et al.¹⁸18 Ferraiolo A, Barra F, Kratochwila C, PaudiceM, Vellone VG, Godano E, et al. Report of positive placental swabs for SARS-CoV-2 in an asymptomatic pregnant woman with COVID-19. Medicina (Kaunas). 2020;56(06):306. Doi: 10.3390/medicina56060306 https://doi.org/10.3390/medicina56060306...	Case report of positive placental swabs for SARS-CoV-2 in an asymptomatic pregnant woman	Placental histological examination did not show substantial macroscopic alterations, except for mild to moderate subchorionic deposition of fibrin, for the presence of a single ischemic area in the thickness of the chorionic disc, for the appearance of villous agglutination, and for multiple organizing intervillous hemorrhages.
Shanes et al.¹⁹19 Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental Pathology in COVID-19. AmJ Clin Pathol. 2020;154(01): 23-32. Doi: 10.1093/ajcp/aqaa089 https://doi.org/10.1093/ajcp/aqaa089...	Case series and comparative study between 16 SARS-CoV-2 infected pregnant women and 2 populations of controls	Third-trimester placentas were significantly more likely to show decidual arteriopathy or at least one characteristic of maternal vascular malperfusion (MVM), such as abnormal or injured maternal vessels and intervillous thrombi, when compared to controls. Placentas were not tested for SARS-CoV-2.
Patanè et al.²⁰20 Patanè L, Morotti D, GiuntaMR, Sigismondi C, Piccoli MG, Frigerio L, et al. Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth. Am J Obstet Gynecol MFM. 2020;2(03):100145. Doi: 10.1016/j.ajogmf.2020.100145 https://doi.org/10.1016/j.ajogmf.2020.10...	Case series of 22 SARS-CoV-2-infected pregnant women in the third trimester	Only two newborns had SARS-CoV-2-positive nasopharyngeal swabs, whose placentas showed chronic intervillositis. On placental histological examination, no significant changes were observed in the other infected pregnant women.
Chen et al.²¹21 Chen S, Huang B, Luo DJ, Li X, Yang F, Zhao Y, Nie X, et al. [Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases]. Zhonghua Bing Li Xue Za Zhi. 2020;49(05):418-423. Doi: 10.3760/cma.j.cn112151-20200225-00138Chinese. https://doi.org/10.3760/cma.j.cn112151-2...	Case series of three SARS-CoV-2-infected pregnant women in the third trimester	Placental histological examination showed various degrees of fibrin deposition inside and around the villi, but no pathological change of villitis or chorioamnionitis. There were no specific placental morphologic changes related to SARS-CoV-2 infection.
Taglauer et al.²²22 Taglauer E, Benarroch Y, Rop K, Barnett E, Sabharwal V, Yarrington C, Wachman EM. Consistent localization of SARS-CoV-2 spike glycoprotein and ACE2 over TMPRSS2 predominance in placental villi of 15 COVID-19 positive maternal-fetal dyads. Placenta. 2020;100:69-74. Doi: 10.1016/j.placenta.2020.08.015 https://doi.org/10.1016/j.placenta.2020....	Case series and comparative study between 15 SARS-CoV-2-infected pregnant women and 10 SARS-CoV-2-negative pregnant women	There were no specific histopathological characteristics in the placentas related to SARS-CoV-2 infection. Placentas from infected women were notable for the presence of signs of inflammation and fibrin deposition, mostly intervillous and subchorionic deposition.

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[1] Address for correspondence Caio Ribeiro Vieira Leal, Avenida Professor Alfredo Balena 110, 4° andar, Santa Efigênia, Belo Horizonte, Minas Gerais, MG, 31100-000, Brazil (e-mail: lealcaiorv@gmail.com).