Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19

Morotti, Denise; Cadamuro, Massimiliano; Rigoli, E; Sonzogni, Aurelio; Gianatti, Andrea; Parolin, Cristina; Patanè, Luisa; Schwartz, David A.

doi:10.3390/pathogens10040479

Cited by 32 publications

(21 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There have been previous individual case reports of both positivity and negativity of Hofbauer cells for SARS-CoV-2 staining, 26,38,63 but this present article describes the first systematic investigation of SARS-CoV-2 involving Hofbauer cells and other cell types in a large cohort of placentas infected with the virus. Evaluation of 22 placentas infected with SARS-CoV-2 revealed that Hofbauer cells were immunohistochemically positive for viral staining in 4 cases (18%) ( Cases 19,15,20,21).…”

Section: Discussionmentioning

confidence: 86%

Hofbauer Cells and COVID-19 in Pregnancy

Schwartz

Baldewijns

Benachi

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

Self Cite

View full text Add to dashboard Cite

Context.– Severe acute respiratory syndrome coronavirus 2 (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 SARSCoV-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 in 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 was present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4/22 placentas (18%). Villous capillary endothelial staining was positive in 2/22 cases (9%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21/22 placentas (95%). Hofbauer cell hyperplasia was present in 3/22 placentas (14%). In the 7 cases having documented transplacental infection of the fetus, 2 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.

show abstract

Section: Discussionmentioning

confidence: 86%

Hofbauer Cells and COVID-19 in Pregnancy

Schwartz

Baldewijns

Benachi

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thorough literature search aimed at including all potentially relevant studies, multitude of histopathological anomalies and the large numbers of included cases 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 represent the main strengths of the present systematic review. The retrospective design of most of the included studies, small sample size, and heterogeneity in histopathological anomalies observed, are the main limitations of this systematic review.…”

Section: Discussionmentioning

confidence: 99%

“… 8 Several reports suggest an increased risk of placental lesions due to hypoperfusion and inflammation in women with SARS-CoV-2 infection. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 The potential association between SARS-CoV-2 and impaired placental function is crucial because it might lead to fetal decompensation and increased risk of perinatal mortality and morbidity. 66 , 67 Despite this, the occurrence of placental histopathological abnormalities in pregnancies complicated by SARS-CoV-2 infection is yet to be fully explored.…”

Section: Introductionmentioning

confidence: 99%

Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis

Girolamo

Khalil

Alameddine

et al. 2021

American Journal of Obstetrics & Gynecology MFM

124

View full text Add to dashboard Cite

Objectives : To report the spectrum of placental pathology findings in pregnancies complicated by SARS-CoV-2 infection. Methods : MEDLINE, EMBASE, Google Scholar and the Web of Science databases were searched up to August 11 th , 2021. Histopathological anomalies included maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), acute inflammatory pathology (AIP), chronic inflammatory pathology (CIP), increased perivillous fibrin and intervillous thrombosis. Sub-analyses including only symptomatic women and high-risk pregnancies were also performed. Histopathological analysis of the placenta included gross examination, histopathology on hematoxylin and eosin (H&E), immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), qRT-PCR on placental tissue, and transmission electron microscope (TEM). Random-effect meta-analyses were used to analyze the data. Results : Fifty-seven studies (1009 pregnancies) were included. MVM was reported in 31.4% (95% CI 21.0-42.8) of placentas, while FVM was observed in 26.9% of cases (95% CI 19.2-35.4). AIP and CIP were reported in 22.6% (95% CI 16.8-28.9) and 26.2% (95% CI 18.9-34.2) of cases, respectively. Increased perivillous fibrin was observed in 32.7% (95% CI 24.1-42.0) of placentas undergoing histopathological analysis, while intervillous thrombosis were observed in 14.6% (95% CI 10.6-21.8) of cases. Other placental findings, including either basal plate with attached myometrial fibers, microscopic accretism, villous edema, increased circulating nucleated Red Blood Cells or membranes with hemorrhage were reported in 38% (95% CI 28.5-48.0) of cases, while only 17.4% (95% CI 10.9-25.0) did not present any abnormal histological findings. Sub-analyses according to maternal symptoms due to SARS-CoV-2 infection or the presence of a high-risk pregnancy showed similar distribution of the different histopathological anomalies to that reported in the main analysis. The risk of placental histopathological anomalies was also higher when considering only case-control studies comparing women with SARS-CoV-2 infection with healthy controls. Conclusions : A significant proportion of placentas where SARS-CoV-2 occurred during pregnancy shows histopathological findings suggesting placental hypoperfusion and inflammation. Future multicenter prospective blinded studies are needed to correlate these placental lesions with pregnancy outcomes.

show abstract

“…The vertical transmission of corona viruses is reported to be rare 4 . Nevertheless, the likelihood of placental transmission can be supported by presence of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in placental epithelium, which are paramount in cellular infiltration of the SARS CoV-2 3 . A systematic review by Kotlyar AM, et al 4 revealed that there is a 3.2% risk of transmitting the virus by infected mothers in the third trimester as confirmed by nasopharyngeal RT-PCR.…”

Section: Discussionmentioning

confidence: 99%