PDF herunterladen
Am J Perinatol 2022; 39(15): 1643-1653
DOI: 10.1055/a-1787-7933
Review Article

Placental Vascular and Inflammatory Findings from Pregnancies Diagnosed with Coronavirus Disease 2019: A Systematic Review and Meta-analysis

Kamran Hessami
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Kjersti M. Aagaard
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Eumenia C. Castro
2   Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Sara E. Arian
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Ahmed A. Nassr
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Enrico R. Barrozo
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Maxim D. Seferovic
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
,
Alireza A. Shamshirsaz
1   Department of Obstetrics and Gynecology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas
› Institutsangaben Funding None.
› Weitere Informationen
    Lizenzen und Reprints

Abstract

We aimed to perform a meta-analysis of the literature concerning histopathologic findings in the placentas of women with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection during pregnancy. Searches for articles in English included PubMed, Web of Science, Google Scholar, and reference lists (up to April 2021). Studies presenting data on placental histopathology according to the Amsterdam Consensus Group criteria in SARS-CoV-2 positive and negative pregnancies were identified. Lesions were categorized into: maternal and fetal vascular malperfusion (MVM and FVM, respectively), acute placental inflammation with maternal and fetal inflammatory response (MIR and FIR, respectively), chronic inflammatory lesions (CILs), and increased perivillous fibrin deposition (PVFD). A total of 15 studies reporting on 19,025 placentas, n = 699 of which were derived from women who were identified as being infected with SARS-CoV-2 and 18,326 as SARS-CoV-2-negative controls, were eligible for analysis. No significant difference in incidence of MVM (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 0.73–1.90), FVM (OR: 1.23, 95% CI: 0.63–2.42), MIR (OR: 0.66, 95% CI: 0.29–1.52) or FIR (OR: 0.85, 95% CI: 0.44–1.63), and CILs (OR: 0.97, 95% CI: 0.55–1.72) was found between placentae from gravida identified as being SARS-CoV-2 infected. However, placenta from gravida identified as being infected with SARS-CoV-2 were associated with significantly increased occurrence of PVFD (OR: 2.77, 95% CI: 1.06–7.27). After subgroup analyses based on clinical severity of COVID-19 infection, no significant difference was observed in terms of reported placental pathology between symptomatic or asymptomatic SARS-CoV-2 gravidae placenta. Current evidence based on the available literature suggests that the only pathologic finding in the placentae of women who are pregnant identified as having been infected with SARS-CoV-2 was an increased prevalence of PVFD.

Key Points

  • No association between SARS-CoV-2 and maternal or fetal placental malperfusion.

  • No association between SARS-CoV-2 and maternal or fetal inflammatory response.

  • SARS-CoV-2 is associated with increased perivillous fibrin deposition in placenta.

Keywords

COVID-19 - SARS-CoV-2 - placenta - pregnancy - pathology - meta-analysis

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author (shamshir@bcm.edu; alirezashamshirsaz@yahoo.com).


Authors' Contributions

K.H. and A.A.S. conceived and designed the study; K.H., E.R.B., M.D.S., and A.A.N. collected the data; K.H. performed the analysis; K.H., K.M.A., and S.E.A. wrote the paper; E.C.C. performed pathological assessment. All authors read the final version and manuscript and approved it for the submission.


Registration

This systematic review and meta-analysis was prospectively PROSPERO (CRD42021251458).


Supplementary Material



Publikationsverlauf

Eingereicht: 12. November 2021

Angenommen: 18. Februar 2022

Accepted Manuscript online:
03. März 2022

Artikel online veröffentlicht:
31. Mai 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Rasmussen SA, Jamieson DJ, Uyeki TM. Effects of influenza on pregnant women and infants. Am J Obstet Gynecol 2012; 207 (3, Suppl): S3-S8
    CrossrefPubMedGoogle Scholar
  • 2 Aagaard-Tillery K, Silver R, Dalton J. Immunology of normal pregnancy. Semin Fetal Neonatal Med 2006; 11: 279-295
    CrossrefPubMedGoogle Scholar
  • 3 Littauer EQ, Skountzou I. Hormonal regulation of physiology, innate immunity and antibody response to H1N1 influenza virus infection during pregnancy. Front Immunol 2018; 9: 2455
    CrossrefPubMedGoogle Scholar
  • 4 Mosby LG, Rasmussen SA, Jamieson DJ. 2009 pandemic influenza A (H1N1) in pregnancy: a systematic review of the literature. Am J Obstet Gynecol 2011; 205 (01) 10-18
    CrossrefPubMedGoogle Scholar
  • 5 Ellington S, Strid P, Tong VT. et al. Characteristics of women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status—United States, January 22–June 7, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (25) 769-775
    CrossrefPubMedGoogle Scholar
  • 6 Wong SF, Chow KM, Leung TN. et al. Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am J Obstet Gynecol 2004; 191 (01) 292-297
    CrossrefPubMedGoogle Scholar
  • 7 Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135 (23) 2033-2040
    CrossrefPubMedGoogle Scholar
  • 8 Patberg ET, Adams T, Rekawek P. et al. Coronavirus disease 2019 infection and placental histopathology in women delivering at term. Am J Obstet Gynecol 2021; 224 (04) 382.e1-382.e18
    CrossrefPubMedGoogle Scholar
  • 9 Zhang P, Heyman T, Greechan M. et al. Maternal, neonatal and placental characteristics of SARS-CoV-2 positive mothers. J Matern Fetal Neonatal Med 2021; •••: 1-9
    Google Scholar
  • 10 Seferovic MD, Turley M, Valentine GC. et al. Clinical importance of placental testing among suspected cases of congenital Zika syndrome. Int J Mol Sci 2019; 20 (03) E712
    CrossrefPubMedGoogle Scholar
  • 11 Seferovic M, Sánchez-San Martín C, Tardif SD. et al. Experimental Zika virus infection in the pregnant common marmoset induces spontaneous fetal loss and neurodevelopmental abnormalities. Sci Rep 2018; 8 (01) 6851
    CrossrefPubMedGoogle Scholar
  • 12 de Noronha L, Zanluca C, Burger M. et al. Zika virus infection at different pregnancy stages: anatomopathological findings, target cells and viral persistence in placental tissues. Front Microbiol 2018; 9: 2266
    CrossrefPubMedGoogle Scholar
  • 13 Schwartz DA. Viral infection, proliferation, and hyperplasia of Hofbauer cells and absence of inflammation characterize the placental pathology of fetuses with congenital Zika virus infection. Arch Gynecol Obstet 2017; 295 (06) 1361-1368
    CrossrefPubMedGoogle Scholar
  • 14 Hirsch AJ, Roberts VHJ, Grigsby PL. et al. Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. Nat Commun 2018; 9 (01) 263
    CrossrefPubMedGoogle Scholar
  • 15 Taglauer E, Benarroch Y, Rop K. et al. 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
    CrossrefPubMedGoogle Scholar
  • 16 Ouyang Y, Bagalkot T, Fitzgerald W. et al. Term human placental trophoblasts express SARS-CoV-2 entry factors ACE2, TMPRSS2, and furin. MSphere 2021; 6 (02) e00250-21
    CrossrefPubMedGoogle Scholar
  • 17 Tallarek A-C, Urbschat C, Fonseca Brito L. et al. Inefficient placental virus replication and absence of neonatal cell-specific immunity upon Sars-CoV-2 infection during pregnancy. Front Immunol 2021; 12 (2047): 698578
    CrossrefPubMedGoogle Scholar
  • 18 Khong TY, Mooney EE, Ariel I. et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group consensus statement. Arch Pathol Lab Med 2016; 140 (07) 698-713
    CrossrefPubMedGoogle Scholar
  • 19 Goldstein JA, Gallagher K, Beck C, Kumar R, Gernand AD. Maternal-fetal inflammation in the placenta and the developmental origins of health and disease. Front Immunol 2020; 11 (2786): 531543
    CrossrefPubMedGoogle Scholar
  • 20 Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol 2015; 213 (4, Suppl): S29-S52
    CrossrefPubMedGoogle Scholar
  • 21 von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Int J Surg 2014; 12 (12) 1495-1499
    CrossrefPubMedGoogle Scholar
  • 22 Rahmani N, Salehi A, Molavi Vardanjani H, Marzban M, Behbood A. Using STROBE checklist to assess the reporting quality of observational studies affiliated with Shiraz University of Medical Sciences, and its correlates: a scientometric study from Iran. Scientometrics 2020; 122 (02) 989-1001
    CrossrefPubMedGoogle Scholar
  • 23 Debelenko L, Katsyv I, Chong AM, Peruyero L, Szabolcs M, Uhlemann AC. Trophoblast damage with acute and chronic intervillositis: disruption of the placental barrier by severe acute respiratory syndrome coronavirus 2. Hum Pathol 2021; 109: 69-79
    CrossrefPubMedGoogle Scholar
  • 24 Edlow AG, Li JZ, Collier AY. et al. 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
    CrossrefPubMedGoogle Scholar
  • 25 Gulersen M, Prasannan L, Tam Tam H. et al. Histopathologic evaluation of placentas after diagnosis of maternal severe acute respiratory syndrome coronavirus 2 infection. Am J Obstet Gynecol MFM 2020; 2 (04) 100211
    CrossrefPubMedGoogle Scholar
  • 26 He M, Skaria P, Kreutz K, Chen L, Hagemann IS, Carter EB, Mysorekar IU, Nelson DM, Pfeifer J, Dehner LP. Histopathology of Third Trimester Placenta from SARS-CoV-2-Positive Women. Fetal Pediatr Pathol 2020; Oct 12: 1-10
    PubMedGoogle Scholar
  • 27 Levitan D, London V, McLaren RA. et al. Histologic and immunohistochemical evaluation of 65 placentas from women with polymerase chain reaction-proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Arch Pathol Lab Med 2021; 145 (06) 648-656
    CrossrefPubMedGoogle Scholar
  • 28 Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental pathology in COVID-19. Am J Clin Pathol 2020; 154 (01) 23-32
    CrossrefPubMedGoogle Scholar
  • 29 Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CB, Lu-Culligan WJ. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med. 2021; May 14 2 (05) 591-610
    CrossrefPubMedGoogle Scholar
  • 30 Blasco Santana L, Miraval Wong E, Álvarez-Troncoso J, Sánchez García L, Bartha JL, Regojo-Zapata RM. Maternal and perinatal outcomes and placental pathologic examination of 29 SARS-CoV-2 infected patients in the third trimester of gestation. J Obstet Gynaecol Res 2021; 47 (06) 2131-2139
    CrossrefPubMedGoogle Scholar
  • 31 Resta L, Vimercati A, Cazzato G. et al. SARS-CoV-2 and placenta: new insights and perspectives. Viruses 2021; 13 (05) 723
    CrossrefPubMedGoogle Scholar
  • 32 Tasca C, Rossi RS, Corti S. et al. Placental pathology in COVID-19 affected pregnant women: a prospective case-control study. Placenta 2021; 110: 9-15
    CrossrefPubMedGoogle Scholar
  • 33 Bertero L, Borella F, Botta G. et al. Placenta histopathology in SARS-CoV-2 infection: analysis of a consecutive series and comparison with control cohorts. Virchows Arch 2021; 479 (04) 715-728
    CrossrefPubMedGoogle Scholar
  • 34 Rebutini PZ, Zanchettin AC, Stonoga ETS. et al. Association between COVID-19 pregnant women symptoms severity and placental morphologic features. Front Immunol 2021; 12: 685919
    CrossrefPubMedGoogle Scholar
  • 35 Jaiswal N, Puri M, Agarwal K. et al. COVID-19 as an independent risk factor for subclinical placental dysfunction. Eur J Obstet Gynecol Reprod Biol 2021; 259: 7-11
    CrossrefPubMedGoogle Scholar
  • 36 Sharps MC, Hayes DJL, Lee S. et al. A structured review of placental morphology and histopathological lesions associated with SARS-CoV-2 infection. Placenta 2020; 101: 13-29
    CrossrefPubMedGoogle Scholar
  • 37 Di Girolamo R, Khalil A, Alameddine S. et al. Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM 2021; 3 (06) 100468
    CrossrefPubMedGoogle Scholar
  • 38 Gadanec LK, McSweeney KR, Qaradakhi T, Ali B, Zulli A, Apostolopoulos V. Can SARS-CoV-2 virus use multiple receptors to enter host cells?. Int J Mol Sci 2021; 22 (03) 992
    CrossrefPubMedGoogle Scholar
  • 39 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 (04) e0230295
    CrossrefPubMedGoogle Scholar
  • 40 Singh M, Bansal V, Feschotte C. A single-cell RNA expression map of human coronavirus entry factors. Cell Rep 2020; 32 (12) 108175
    CrossrefPubMedGoogle Scholar
  • 41 Ashary N, Bhide A, Chakraborty P. et al. Single-cell RNA-seq identifies cell subsets in human placenta that highly expresses factors driving pathogenesis of SARS-CoV-2. Front Cell Dev Biol 2020; 8: 783
    CrossrefPubMedGoogle Scholar
  • 42 Cui D, Liu Y, Jiang X. et al. Single-cell RNA expression profiling of SARS-CoV-2-related ACE2 and TMPRSS2 in human trophectoderm and placenta. Ultrasound Obstet Gynecol 2021; 57 (02) 248-256
    CrossrefPubMedGoogle Scholar
  • 43 Zheng Q-L, Duan T, Jin L-P. Single-cell RNA expression profiling of ACE2 and AXL in the human maternal–fetal interface. Reprod Dev Med 2020; 4 (01) 7-10
    CrossrefPubMedGoogle Scholar
  • 44 Faure-Bardon V, Isnard P, Roux N. et al. Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling. Ultrasound Obstet Gynecol 2021; 57 (02) 242-247
    CrossrefPubMedGoogle Scholar
  • 45 Pique-Regi R, Romero R, Tarca AL. et al. Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?. eLife 2020; 9: e58716
    CrossrefPubMedGoogle Scholar
  • 46 Malinowski AK, Noureldin A, Othman M. COVID-19 susceptibility in pregnancy: Immune/inflammatory considerations, the role of placental ACE-2 and research considerations. Reprod Biol 2020; 20 (04) 568-572
    CrossrefPubMedGoogle Scholar
  • 47 Blair RV, Vaccari M, Doyle-Meyers LA. et al. Acute respiratory distress in aged, SARS-CoV-2-infected african green monkeys but not rhesus macaques. Am J Pathol 2021; 191 (02) 274-282
    CrossrefPubMedGoogle Scholar
  • 48 Körner RW, Majjouti M, Alcazar MAA, Mahabir E. Of mice and men: the coronavirus MHV and mouse models as a translational approach to understand SARS-CoV-2. Viruses 2020; 12 (08) 880
    CrossrefPubMedGoogle Scholar