Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethical Statement
2.2. Patient History
2.3. Hematoxylin and Eosin Staining
2.4. Immunohistochemical Staining
2.5. RNA In Situ Hybridization
2.6. Double Staining Immunohistochemistry for CD163/RNA In Situ Hybridization for SARS-CoV-2
2.7. RNAscope Image Acquisition and Data Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Schwartz, D.A. An Analysis of 38 Pregnant Women with COVID-19, Their Newborn Infants, and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes. Arch. Pathol. Lab. Med. 2020, 144, 799–805. [Google Scholar] [CrossRef] [Green Version]
- Schwartz, D.A.; Graham, A.L. Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women: Lessons from SARS, MERS, and Other Human Coronavirus Infections. Viruses 2020, 12, 194. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schwartz, D.A.; Dhaliwal, A. Infections in Pregnancy With COVID-19 and Other Respiratory RNA Virus Diseases Are Rarely, If Ever, Transmitted to the Fetus: Experiences with Coronaviruses, Parainfluenza, Metapneumovirus Respiratory Syncytial Virus, and Influenza. Arch. Pathol. Lab. Med. 2020, 144, 920–928. [Google Scholar] [CrossRef]
- Meslin, P.; Guiomard, C.; Chouakria, M.; Porcher, J.; Duquesne, F.; Tiprez, C.; Zemouri, N. Coronavirus Disease 2019 in Newborns and Very Young Infants. Pediatr. Infect. Dis. J. 2020, 39, e145–e147. [Google Scholar] [CrossRef]
- Oncel, M.Y.; Akın, I.M.; Kanburoglu, M.K.; Tayman, C.; Coskun, S.; Narter, F.; Er, I.; Oncan, T.G.; Memisoglu, A.; Oguz, D.; et al. A multicenter study on epidemiological and clinical characteristics of 125 newborns born to women infected with COVID-19 by Turkish Neonatal Society. Eur. J. Nucl. Med. Mol. Imaging 2021, 180, 733–742. [Google Scholar] [CrossRef]
- Schwartz, D.A.; Mohagheghi, P.; Beigi, B.; Zafaranloo, N.; Moshfegh, F.; Yazdani, A. Spectrum of neonatal COVID-19 in Iran: 19 infants with SARS-CoV-2 perinatal infections with varying test results, clinical findings and outcomes. J. Matern. Neonatal Med. 2020. [Google Scholar] [CrossRef]
- Huntley, B.J.F.; Huntley, E.S.; Di Mascio, D.; Chen, T.; Berghella, V.; Chauhan, S.P. Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2) Infection. Obstet. Gynecol. 2020, 136, 303–312. [Google Scholar] [CrossRef]
- Auriti, C.; De Rose, D.U.; Tzialla, C.; Caforio, L.; Ciccia, M.; Manzoni, P.; Stronati, M. Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences? Am. J. Perinatol. 2020, 37, S31–S38. [Google Scholar] [CrossRef]
- Lamouroux, A.; Attie-Bitach, T.; Martinovic, J.; Leruez-Ville, M.; Ville, Y. Evidence for and against vertical transmission for severe acute respiratory syndrome coronavirus 2. Am. J. Obstet. Gynecol. 2020, 223, 91.e1–91.e4. [Google Scholar] [CrossRef]
- Vivanti, A.J.; Vauloup-Fellous, C.; Prevot, S.; Zupan, V.; Suffee, C.; Cao, J.D.; Benachi, A.; De Luca, D. Transplacental transmission of SARS-CoV-2 infection. Nat. Commun. 2020, 11, 3572. [Google Scholar] [CrossRef]
- Patanè, L.; Morotti, D.; Giunta, M.R.; Sigismondi, C.; Piccoli, M.G.; Frigerio, L.; Mangili, G.; Arosio, M.; Cornolti, G. 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, 100145. [Google Scholar] [CrossRef]
- Facchetti, F.; Bugatti, M.; Drera, E.; Tripodo, C.; Sartori, E.; Cancila, V.; Papaccio, M.; Castellani, R.; Casola, S.; Boniotti, M.B.; et al. 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. [Google Scholar] [CrossRef]
- Stonoga, E.T.S.; Lanzoni, L.D.A.; Rebutini, P.Z.; de Oliveira, A.L.P.; Chiste, J.A.; Fugaça, C.A.; Prá, D.M.M.; Percicote, A.P.; Rossoni, A.; Nogueira, M.B.; et al. Intrauterine Transmission of SARS-CoV-2. Emerg. Infect. Dis. 2021, 27, 638–641. [Google Scholar] [CrossRef]
- Sisman, J.; Jaleel, M.A.; Moreno, W.; Rajaram, V.; Collins, R.R.; Savani, R.C.; Rakheja, D.; Evans, A.S. Intrauterine Transmission of SARS-COV-2 Infection in a Preterm Infant. Pediatr. Infect. Dis. J. 2020, 39, e265–e267. [Google Scholar] [CrossRef]
- Pulinx, B.; Kieffer, D.; Michiels, I.; Petermans, S.; Strybol, D.; Delvaux, S.; Baldewijns, M.; Raymaekers, M.; Cartuyvels, R.; Maurissen, W. Vertical transmission of SARS-CoV-2 infection and preterm birth. Eur. J. Clin. Microbiol. Infect. Dis. 2020, 39, 2441–2445. [Google Scholar] [CrossRef]
- Schwartz, D.A.; Morotti, D.; Beigi, B.; Moshfegh, F.; Zafaranloo, N.; Patanè, L. Confirming Vertical Fetal Infection with Coronavirus Disease 2019: Neonatal and Pathology Criteria for Early Onset and Transplacental Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 From Infected Pregnant Mothers. Arch. Pathol. Lab. Med. 2020, 144, 1451–1456. [Google Scholar] [CrossRef]
- Schwartz, D.A.; Thomas, K.M. Characterizing COVID-19 maternal-fetal transmission and placental infection using comprehensive molecular pathology. EBioMedicine 2020, 60, 102983. [Google Scholar] [CrossRef]
- Schwartz, D.A.; Morotti, D. Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2. Viruses 2020, 12, 1308. [Google Scholar] [CrossRef]
- Schwartz, D.A.; Baldewijns, M.; Benachi, A.; Bugatti, T.M.; Collins, R.R.; De Luca, D.; Facchetti, F.; Linn, R.L.; Marcelis, L.; Morotti, B.D.; et al. Chronic Histiocytic Intervillositis with Trophoblast Necrosis are Risk Factors Associated with Placental Infection from Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Liveborn and Stillborn Infants. Arch. Pathol. Lab. Med. 2020. [Google Scholar] [CrossRef]
- Mezouar, S.; Katsogiannou, M.; Ben Amara, A.; Bretelle, F.; Mege, J.-L. Placental macrophages: Origin, heterogeneity, function and role in pregnancy-associated infections. Placenta 2021, 103, 94–103. [Google Scholar] [CrossRef]
- Castellucci, M.; Zaccheo, D.; Pescetto, G. A three-dimensional study of the normal human placental villous core. Cell Tissue Res. 1980, 210, 235–247. [Google Scholar] [CrossRef] [PubMed]
- Castellucci, M.; Celona, A.; Bartels, H.; Steininger, B.; Benedetto, V.; Kaufmann, P. Mitosis of the Hofbauer cell: Possible implications for a fetal macrophage. Placenta 1987, 8, 65–76. [Google Scholar] [CrossRef]
- Schliefsteiner, C.; Peinhaupt, M.; Kopp, S.; Lögl, J.; Lang-Olip, I.; Hiden, U.; Heinemann, A.; Desoye, G.; Wadsack, C. Human Placental Hofbauer Cells Maintain an Anti-inflammatory M2 Phenotype despite the Presence of Gestational Diabetes Mellitus. Front. Immunol. 2017, 8, 888. [Google Scholar] [CrossRef] [Green Version]
- Sharps, M.C.; Baker, B.C.; Guevara, T.; Bischof, H.; Jones, R.L.; Greenwood, S.L.; Heazell, A.E.P. Increased placental macrophages and a pro-inflammatory profile in placentas and maternal serum in infants with a decreased growth rate in the third trimester of pregnancy. Am. J. Reprod. Immunol. 2020, 84, e13267. [Google Scholar] [CrossRef] [PubMed]
- Reyes, L.; Golos, T.G. Hofbauer Cells: Their Role in Healthy and Complicated Pregnancy. Front. Immunol. 2018, 9, 2628. [Google Scholar] [CrossRef] [Green Version]
- Zulu, M.Z.; Martinez, F.O.; Gordon, S.; Gray, C.M. The Elusive Role of Placental Macrophages: The Hofbauer Cell. J. Innate Immun. 2019, 11, 447–456. [Google Scholar] [CrossRef]
- Schliefsteiner, C.; Ibesich, S.; Wadsack, C. Placental Hofbauer Cell Polarization Resists Inflammatory Cues In Vitro. Int. J. Mol. Sci. 2020, 21, 736. [Google Scholar] [CrossRef] [Green Version]
- Gaw, S.L.; Hromatka, B.S.; Ngeleza, S.; Buarpung, S.; Ozarslan, N.; Tshefu, A.; Fisher, S.J. Differential Activation of Fetal Hofbauer Cells in Primigravidas is Associated with Decreased Birth Weight in Symptomatic Placental Malaria. Malar. Res. Treat. 2019, 2019, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Schwartz, D.A. 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, 1361–1368. [Google Scholar] [CrossRef] [PubMed]
- Rosenberg, A.Z.; Yu, W.; Hill, D.A.; Reyes, C.A.; Schwartz, D.A. Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia. Arch. Pathol. Lab. Med. 2017, 141, 43–48. [Google Scholar] [CrossRef] [Green Version]
- Bittencourt, A.L.; Garcia, A.G.P. THE Placenta in Hematogenous Infections. Pediatr. Pathol. Mol. Med. 2002, 21, 401–432. [Google Scholar] [CrossRef]
- Eissa, M.H.; Abdelsalam, A.M.; Herez, H.A.; Younis, T.A.; Morsy, T.A. Placental villous maturation in patients with re-peated abortions and chronic toxoplasmosis. J. Egypt. Soc. Parasitol. 1990, 20, 661–666. [Google Scholar] [PubMed]
- Heerema-McKenney, A. Defense and infection of the human placenta. APMIS 2018, 126, 570–588. [Google Scholar] [CrossRef] [Green Version]
- Johnson, E.L.; Chakraborty, R. Placental Hofbauer cells limit HIV-1 replication and potentially offset mother to child transmission (MTCT) by induction of immunoregulatory cytokines. Retrovirology 2012, 9, 101. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Johnson, E.L.; Chu, H.; Byrareddy, S.N.; Spearman, P.; Chakraborty, R. Placental Hofbauer cells assemble and sequester HIV-1 in tetraspanin-positive compartments that are accessible to broadly neutralizing antibodies. J. Int. Aids Soc. 2015, 18, 19385. [Google Scholar] [CrossRef]
- Simoni, M.K.; Jurado, K.A.; Abrahams, V.M.; Fikrig, E.; Guller, S. Zika virus infection of Hofbauer cells. Am. J. Reprod. Immunol. 2017, 77, e12613. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ritter, J.M.; Martines, R.B.; Zaki, S.R. Zika Virus: Pathology from the Pandemic. Arch. Pathol. Lab. Med. 2016, 141, 49–59. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raschetti, R.; Vivanti, A.J.; Vauloup-Fellous, C.; Loi, B.; Benachi, A.; De Luca, D. Synthesis and systematic review of reported neonatal SARS-CoV-2 infections. Nat. Commun. 2020, 11, 5164. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Definition and Categorization of the Timing of Mother-to-Child Transmission of SARS-CoV-2. WHO Scientific Brief. Available online: https://www.who.int/publications/i/item/WHO-2019-nCoV-mother-to-child-transmission-2021.1 (accessed on 9 February 2021).
- Schwartz, D.A.; De Luca, D. The Public Health and Clinical Importance of Accurate Neonatal Testing for COVID-19. Pediatrics 2021, 147, 2020036871. [Google Scholar] [CrossRef]
- Debelenko, L.; Katsyv, I.; Chong, A.M.; Peruyero, L.; Szabolcs, M.; Uhlemann, A.-C. 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. [Google Scholar] [CrossRef] [PubMed]
- 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, e0230295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Merad, M.; Martin, J.C. Pathological inflammation in patients with COVID-19: A key role for monocytes and macrophages. Nat. Rev. Immunol. 2020, 20, 355–362. [Google Scholar] [CrossRef] [PubMed]
- Abassi, Z.; Knaney, Y.; Karram, T.; Heyman, S.N. The Lung Macrophage in SARS-CoV-2 Infection: A Friend or a Foe? Front. Immunol. 2020, 11, 1312. [Google Scholar] [CrossRef] [PubMed]
- Keidar, S.; Strizevsky, A.; Raz, A.; Gamliel-Lazarovich, A. ACE2 activity is increased in monocyte-derived macrophages from prehypertensive subjects. Nephrol. Dial. Transplant. 2006, 22, 597–601. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feng, Z.; Diao, B.; Wang, R.; Wang, G.; Wang, C.; Tan, Y.; Liu, L.; Wang, C.; Liu, Y.; Liu, Y.; et al. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly decimates human spleens and lymph nodes. medRxiv 2021. [Google Scholar] [CrossRef]
- Hecht, J.L.; Quade, B.; Deshpande, V.; Mino-Kenudson, M.; Ting, D.T.; Desai, N.; Dygulska, B.; Heyman, T.; Salafia, C.; Shen, D.; et al. SARS-CoV-2 can infect the placenta and is not associated with specific placental histo-pathology: A series of 19 placentas from COVID-19-positive mothers. Mod. Pathol. 2020, 33, 2092–2103. [Google Scholar] [CrossRef] [PubMed]
- Gengler, C.; Dubruc, E.; Favre, G.; Greub, G.; de Leval, L.; Baud, D. SARS-CoV-2 ACE-receptor detection in the placenta throughout pregnancy. Clin. Microbiol. Infect. 2021, 27, 489–490. [Google Scholar] [CrossRef] [PubMed]
- Schwartz, D.A.; Levitan, D. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting pregnant women and the fetus, intrauterine transmission and placental pathology during the coronavirus disease 2019 (COVID-19) pandemic: It’s complicated. Arch. Pathol. Lab. Med. 2021. in print. [Google Scholar]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Morotti, D.; Cadamuro, M.; Rigoli, E.; Sonzogni, A.; Gianatti, A.; Parolin, C.; Patanè, L.; Schwartz, D.A. Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19. Pathogens 2021, 10, 479. https://doi.org/10.3390/pathogens10040479
Morotti D, Cadamuro M, Rigoli E, Sonzogni A, Gianatti A, Parolin C, Patanè L, Schwartz DA. Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19. Pathogens. 2021; 10(4):479. https://doi.org/10.3390/pathogens10040479
Chicago/Turabian StyleMorotti, Denise, Massimiliano Cadamuro, Elena Rigoli, Aurelio Sonzogni, Andrea Gianatti, Cristina Parolin, Luisa Patanè, and David A. Schwartz. 2021. "Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19" Pathogens 10, no. 4: 479. https://doi.org/10.3390/pathogens10040479