Hofbauer cells and COVID-19 in pregnancy: Molecular pathology analysis of villous macrophages, endothelial cells, and placental findings from 22 placentas infected by SARS-CoV-2 with and without fetal transmission

David A. Schwartz, Marcella Baldewijns, Alexandra Benachi, Mattia Bugatti, Gaetano Bulfamante, Ke Cheng, Rebecca R.J. Collins, Larisa Debelenko, Danièle de Luca, Fabio Facchetti, Brendan Fitzgerald, Daniel Levitan, Rebecca L. Linn, Lukas Marcelis, Denise Morotti, Raffaella Morotti, Luisa Patanè, Sophie Prevot, Bianca Pulinx, Ali G. SaadSam Schoenmakers, David Strybol, Kristen Thomas, Delfina Tosi, Valentina Toto, Lotte E. van der Meeren, Robert M. Verdijk, Alexandre J. Vivanti, Mehreen Zaigham

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Context.-SARS-CoV-2 can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARS-CoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases, including HIV and Zika virus, but their involvement in SARS-CoV-2 is unknown. Objective.-To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium, and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.-Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast, and other fetal-derived cells. Results.-Chronic histiocytic intervillositis and trophoblast necrosis were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.-SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

Original languageEnglish (US)
Pages (from-to)1328-1340
Number of pages13
JournalArchives of Pathology and Laboratory Medicine
Volume145
Issue number11
DOIs
StatePublished - Nov 2021

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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