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 Saad; Sam Schoenmakers; David Strybol; Kristen Thomas; Delfina Tosi; Valentina Toto; Lotte E van der Meeren; Robert M Verdijk; Alexandre J Vivanti; Mehreen Zaigham

doi:10.5858/arpa.2021-0296-SA

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 Saad

Sam Schoenmakers, David Strybol, Kristen Thomas, Delfina Tosi, Valentina Toto, Lotte E van der Meeren, Robert M Verdijk, Alexandre J Vivanti, Mehreen Zaigham

^*Corresponding author for this work

Medical College of Georgia
University Hospitals Leuven
Hopitaux Universitaires Paris-Saclay
University of Brescia
University "La Statale" di Milan
Histowiz, Inc.
University of Texas Southwestern Medical Center
Columbia University Irving Medical Center
Université Paris-Saclay
Pathology Unit
Mercy University Hospital and University College Cork
SUNY Downstate Medical Center
Perelman School of Medicine & Children's Hospital of Philadelphia
Department of Pathology
Papa Giovanni XXIII Hospital
Yale University School of Medicine
Sint-Trudo Hospital
University of Miami Miller School of Medicine/Jackson Health System/Holtz Children's Hospital
New York University School of Medicine
Hospital Complex for Pathological Anatomy and Medical Genetics
Antoine Beclere Hospital
Lund University
Leiden University Medical Centre
University Medical Centre Utrecht

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	1328-1340
Number of pages	13
Journal	Archives of Pathology and Laboratory Medicine
Volume	145
Issue number	11
Early online date	23 Jul 2021
DOIs	https://doi.org/10.5858/arpa.2021-0296-SA
Publication status	Published - Nov 2021

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Schwartz, D. A., Baldewijns, M., Benachi, A., Bugatti, M., Bulfamante, G., Cheng, K., Collins, R. R. J., Debelenko, L., De Luca, D., Facchetti, F., Fitzgerald, B., Levitan, D., Linn, R. L., Marcelis, L., Morotti, D., Morotti, R., Patanè, L., Prevot, S., Pulinx, B., ... Zaigham, M. (2021). 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. Archives of Pathology and Laboratory Medicine, 145(11), 1328-1340. https://doi.org/10.5858/arpa.2021-0296-SA

Schwartz, David A ; Baldewijns, Marcella ; Benachi, Alexandra et al. / 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. In: Archives of Pathology and Laboratory Medicine. 2021 ; Vol. 145, No. 11. pp. 1328-1340.

@article{824f8d7be4514b9196c1a82d39a30296,

title = "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",

abstract = "CONTEXT.{\textemdash}: 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.{\textemdash}: 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.{\textemdash}: 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.{\textemdash}: 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.{\textemdash}: 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.",

author = "Schwartz, \{David A\} and Marcella Baldewijns and Alexandra Benachi and Mattia Bugatti and Gaetano Bulfamante and Ke Cheng and Collins, \{Rebecca R J\} and Larisa Debelenko and \{De Luca\}, Dani{\`e}le and Fabio Facchetti and Brendan Fitzgerald and Daniel Levitan and Linn, \{Rebecca L\} and Lukas Marcelis and Denise Morotti and Raffaella Morotti and Luisa Patan{\`e} and Sophie Prevot and Bianca Pulinx and Saad, \{Ali G\} and Sam Schoenmakers and David Strybol and Kristen Thomas and Delfina Tosi and Valentina Toto and \{van der Meeren\}, \{Lotte E\} and Verdijk, \{Robert M\} and Vivanti, \{Alexandre J\} and Mehreen Zaigham",

year = "2021",

month = nov,

doi = "10.5858/arpa.2021-0296-SA",

language = "English",

volume = "145",

pages = "1328--1340",

journal = "Archives of Pathology and Laboratory Medicine",

issn = "0003-9985",

publisher = "College of American Pathologists",

number = "11",

}

Schwartz, DA, Baldewijns, M, Benachi, A, Bugatti, M, Bulfamante, G, Cheng, K, Collins, RRJ, Debelenko, L, De Luca, D, Facchetti, F, Fitzgerald, B, Levitan, D, Linn, RL, Marcelis, L, Morotti, D, Morotti, R, Patanè, L, Prevot, S, Pulinx, B, Saad, AG, Schoenmakers, S, Strybol, D, Thomas, K, Tosi, D, Toto, V, van der Meeren, LE , Verdijk, RM, Vivanti, AJ & Zaigham, M 2021, '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', Archives of Pathology and Laboratory Medicine, vol. 145, no. 11, pp. 1328-1340. https://doi.org/10.5858/arpa.2021-0296-SA

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. / Schwartz, David A; Baldewijns, Marcella; Benachi, Alexandra et al.
In: Archives of Pathology and Laboratory Medicine, Vol. 145, No. 11, 11.2021, p. 1328-1340.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Hofbauer cells and COVID-19 in pregnancy

T2 - Molecular pathology analysis of villous macrophages, endothelial cells, and placental findings from 22 placentas infected by SARS-CoV-2 with and without fetal transmission

AU - Schwartz, David A

AU - Baldewijns, Marcella

AU - Benachi, Alexandra

AU - Bugatti, Mattia

AU - Bulfamante, Gaetano

AU - Cheng, Ke

AU - Collins, Rebecca R J

AU - Debelenko, Larisa

AU - De Luca, Danièle

AU - Facchetti, Fabio

AU - Fitzgerald, Brendan

AU - Levitan, Daniel

AU - Linn, Rebecca L

AU - Marcelis, Lukas

AU - Morotti, Denise

AU - Morotti, Raffaella

AU - Patanè, Luisa

AU - Prevot, Sophie

AU - Pulinx, Bianca

AU - Saad, Ali G

AU - Schoenmakers, Sam

AU - Strybol, David

AU - Thomas, Kristen

AU - Tosi, Delfina

AU - Toto, Valentina

AU - van der Meeren, Lotte E

AU - Verdijk, Robert M

AU - Vivanti, Alexandre J

AU - Zaigham, Mehreen

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85113770626

U2 - 10.5858/arpa.2021-0296-SA

DO - 10.5858/arpa.2021-0296-SA

M3 - Article

C2 - 34297794

AN - SCOPUS:85113770626

SN - 0003-9985

VL - 145

SP - 1328

EP - 1340

JO - Archives of Pathology and Laboratory Medicine

JF - Archives of Pathology and Laboratory Medicine

IS - 11

ER -

Schwartz DA, Baldewijns M, Benachi A, Bugatti M, Bulfamante G, Cheng K et al. 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. Archives of Pathology and Laboratory Medicine. 2021 Nov;145(11):1328-1340. Epub 2021 Jul 23. doi: 10.5858/arpa.2021-0296-SA

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

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