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. 2021 Nov 1;145(11):1328-1340.
doi: 10.5858/arpa.2021-0296-SA.

Hofbauer Cells and COVID-19 in Pregnancy

David A Schwartz  1 , Marcella Baldewijns  2 , Alexandra Benachi  3 , Mattia Bugatti  4 , Gaetano Bulfamante  5 , Ke Cheng  6 , Rebecca R J Collins  7 , Larisa Debelenko  8 , Danièle De Luca  9 , Fabio Facchetti  10 , Brendan Fitzgerald  11 , Daniel Levitan  12 , Rebecca L Linn  13 , Lukas Marcelis  14 , Denise Morotti  15 , Raffaella Morotti  16 , Luisa Patanè  17 , Sophie Prevot  18 , Bianca Pulinx  19 , Ali G Saad  20 , Sam Schoenmakers  21 , David Strybol  22 , Kristen Thomas  23 , Delfina Tosi  24 , Valentina Toto  25 , Lotte E van der Meeren  26   27 , Robert M Verdijk  28 , Alexandre J Vivanti  29 , Mehreen Zaigham  30
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Free article

Hofbauer Cells and COVID-19 in Pregnancy

David A Schwartz et al. Arch Pathol Lab Med. .
Free article

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.

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