SARS-CoV-2 infection of the placenta

Hosier, Hillary; Farhadian, Shelli; Morotti, Raffaella; Deshmukh, Uma; Lu-Culligan, Alice; Campbell, Katherine; Yasumoto, Yuki; Vogels, Chantal B.F.; Casanovas‐Massana, Arnau; Vijayakumar, Pavithra; Geng, Bertie; Odio, Camila D.; Fournier, John; Fauver, Joseph R.; Liu, Feimei; Alpert, Tara; Tal, Reshef; Szigeti‐Buck, Klara; Perincheri, Sudhir; Larsen, Christopher P.; Gariepy, Aileen M.; Aguilar, Gabriela; Fardelmann, Kristen L.; Harigopal, Malini; Taylor, Hugh S.; Pettker, Christian M.; Wyllie, Anne L.; Cruz, Charles S. Dela; Ring, Aaron M.; Grubaugh, Nathan D.; Ko, Albert Icksang; Horváth, Tamas L.; Iwasaki, Akiko; Reddy, Uma M.; Lipkind, Heather S.

doi:10.1101/2020.04.30.20083907

Cited by 176 publications

(331 citation statements)

References 22 publications

Supporting

Mentioning

278

Contrasting

Unclassified

Order By: Relevance

“…Thus, we finally used single-cell analysis of the syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblasts -the fetal component of the placenta -that confirmed the low-levels of expression of the canonical entry receptor ACE2 and TMPRSS2 genes (21,22). Conversely, we found that these cells express high-levels of DPP4 and CTSL, two potential mediators of SARS-Cov-2 host cell entry (27,30) that may contribute to the SARS-CoV-2 infection (17,25,26). It is essential to highlight that our scRNA-Seq analysis showed that the non-canonical DPP4 and CTSL entry genes (27,30) are highly co-expressed in syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblasts cells.…”

Section: Discussionsupporting

confidence: 74%

“…Recent literature has shown placenta cells infected with SARS-CoV-2 in pregnant women diagnosed with moderate to severe COVID-19 (17,25) with findings supporting the possibility of vertical transmission of SARS-CoV-2 (17,26). However, few placenta cells express ACE2 and TMPRSS2 (21,22) required for virus entry, raising the question about whether potential non-canonical molecular mechanisms may be involved in the biological cycle of the virus in these cells.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Constantino

Cury

Nogueira

et al. 2020

Preprint

View full text Add to dashboard Cite

The SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The data available about COVID-19 during pregnancy have demonstrated placental infection; however, the intrauterine transmission of SARS-CoV-2 is still debated. Intriguingly, while canonical SARS-CoV-2 cell entry mediators are expressed at low levels in placental cells, the receptors for viruses that cause congenital infections such as the cytomegalovirus and Zika virus are highly expressed in these cells. Here we analyzed the transcriptional profile (microarray and single-cell RNA-Seq) of proteins potentially interacting with coronaviruses to identify non-canonical mediators of SARS-CoV-2 infection and replication in the placenta. We show that, despite low levels of the canonical cell entry mediators ACE2 and TMPRSS2, villous trophoblast cells co-express high levels of the potential non-canonical cell-entry mediators DPP4 and CTSL. We also found changes in the expression of DAAM1 and PAICS genes during pregnancy, which are translated into proteins also predicted to interact with coronaviruses proteins. These results provide new insight into the interaction between SARS-CoV-2 and host proteins that may act as non-canonical routes for SARS-CoV-2 infection and replication in the placenta cells.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 91%

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Constantino

Cury

Nogueira

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…However, a recent report of 244 consecutive COVID-19 positive children from Wuhan did not find any difference in fecal nucleic acid RT-PCR between children with or without GI symptoms, suggesting that RT-PCR detection of the virus was not due to gut infection but coming instead from the respiratory tract from swallowed sputum 8 . Defining the role of the GI tract in SARS-CoV-2 infection may also help understand the risks of vertical transmission during gestation since amniotic fluid is swallowed by the fetus during gestation and viral contamination has been isolated from the placenta of an affected woman 9 . While samples from affected mothers have so far failed to prove that amniotic fluid, cord blood, and breast milk contain SARS-CoV-2 10 , very limited data are available at this stage for pregnant women with COVID-19, and even fewer data are available on intrauterine vertical transmission 11 .…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids

Giobbe

Bonfante

Zambaiti

et al. 2020

Preprint

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.

show abstract

“…This literature review comprises 45 COVID-19 positive pregnant women whose placentas and neonates were also analysed by RT-PCR for the presence of SARS-CoV-2. We report no maternal mortality [9][10][11][12][13][14][15][16][17][18][19].…”

Section: Maternal Outcomementioning

confidence: 99%

“…One woman opted for termination of pregnancy due to symptomatic SARS-CoV-2 complicated by severe preeclampsia in the second trimester [15]. Another woman with symptomatic SARS-CoV-2 presented in the second trimester with a miscarriage [17].…”

Section: Maternal Outcomementioning

confidence: 99%

Significance of placental swab in diagnosing vertical transmission in SARS-CoV-2 positive mothers.

Sweeney

Assaf

Khan

2020

Preprint

View full text Add to dashboard Cite

AimsCurrently, there is limited date on the effects of COVID-19 on pregnancy and neonatal outcome. This literature review aims to investigate the possibility of fetal vertical transmission in COVID-19 positive pregnant mothers by diagnosing through placental swabs.MethodsThe search terms ‘pregnant COVID-19 positive mothers’, ‘fetal vertical transmission’ and ‘placental swabs’ were used. 11 papers were selected for this review.ResultsThis literature review comprises 45 COVID-19 positive pregnant women whose placentas and neonates were also analysed by RT-PCR for the presence of SARS-CoV-2. 43 neonates were successfully delivered primarily via caesarean section out of 45 expectant mothers (96%). 2 mothers did not deliver due to severe preeclampsia and a miscarriage both occurring in the second trimester. 3 neonates tested positive for SARS-CoV-2 (7%). We report no neonatal mortality after birth and no maternal mortality. 8 female’s placentas tested positive for SARS-CoV-2 out of a total of 45 tested (18%). Of these 8, 2 cases of SARS-CoV-2 were identified in the maternal, neonatal and placental tissue.ConclusionAfter reviewing multiple studies and investigating the nature of placental physiology in SARS-CoV-2 positive mothers we conclude that there is no concrete evidence of vertical transmission occurring between mother and infant. However, there are inconsistencies across the different papers used for this review and further research investigating the effects of COVID-19 on pregnant women by using RT-PCR to test the mother, placenta, vaginal fluid, breast milk and infant for SARS-CoV-2 at various stages of transmission is urgently needed.

show abstract

SARS-CoV-2 infection of the placenta

Cited by 176 publications

References 22 publications

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

Prediction of non-canonical routes for SARS-CoV-2 infection in human placenta cells

SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids

Significance of placental swab in diagnosing vertical transmission in SARS-CoV-2 positive mothers.

Contact Info

Product

Resources

About