Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019–positive mothers and neonates at birth

Patanè, Luisa; Morotti, Denise; Giunta, M R; Sigismondi, Cristina; Piccoli, Maria Giovanna; Frigerio, Luigi; Mangili, Giovanna; Arosio, Marco; Cornolti, Giorgio

doi:10.1016/j.ajogmf.2020.100145

Cited by 296 publications

(426 citation statements)

References 6 publications

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“…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 . While severe symptoms and death have been recorded in infants as young as 10 months of age 12 , very few cases of pathology in neonates have been associated with infection 13 and when 6 newborns from infected mothers were screened for SARS-CoV-2, they tested negative for the virus 10 .…”

Section: Introductionmentioning

confidence: 99%

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

Giobbe

Bonfante

Zambaiti

et al. 2020

Preprint

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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.

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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

show abstract

“…Of these 8, Patanè et al's study is the rst and only study we have identi ed which reports 2 cases of SARS-CoV-2 in the maternal, neonatal and placental tissue. Both of these mothers displayed signs and symptoms of SARS-CoV-2 [14]. Pen eld et al reported 3 positive placentas in women with severe to critical SARS-CoV-2 [13].…”

Section: Laboratory Investigationsmentioning

confidence: 95%

“…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%

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

Sweeney

Assaf

Khan

2020

Preprint

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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.

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“…The current coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised, among many others, major concerns regarding the impact of infection during pregnancy. As of the time of this writing vertical SARS-COV-2 transmission remains controversial, while viral RNA has been detected in some placentas of COVID-19-affected mothers suggesting placental infection [1][2][3]. Emerging data on COVID-19-induced placental pathology are still limited [4,5].…”

Section: Introductionmentioning

confidence: 99%

Further placental pathology in mild COVID-19 of term pregnancy with pathophysiological correlates

Konstantinidou¹,

Papaevangelou²,

Tsakris³

et al. 2020

Preprint

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Abstract Placental pathology related to SARS-COV-2 infection during pregnancy is under investigation, with emerging but still limited and variable data, mainly including changes of fetal and maternal vascular malperfusion. We observed novel pathological findings not previously reported in two term placentas delivered from women mildly affected with COVID-19, with a 2-day and 6-day interval between the onset of symptoms and delivery. The main changes involved the maternal more than the fetal components of the placenta and included a tendency toward thrombosis and fibrin formation, and mild maternal malperfusion. We further observed fibrin degeneration in the intervillous space, the presence of particles of undetermined origin, and mild or moderate maternal decidual inflammatory exudates consisting of monocytes, macrophages, T-lymphocytes, and plasmacytes. Mild inflammation and incipient mural thrombus formation were noted in the fetal vasculature, as well as endothelial vacuolation of the umbilical vessels, not previously described. The maternal changes were more prominent in the case with a relatively longer clinical manifestation-to-delivery interval, and were associated to a prolonged postpartum maternal viral carriage of 30 days and the development of a low-grade febrile response in the neonate. Both infants showed mild morbidity but eventually had a very good outcome. RT-PCR was negative for SARS-CoV-2 RNA in both cases.We concluded that placental involvement in mild COVID-19 of very short duration at term pregnancy suggested the systemic nature of the disease and appeared related to, though not pathognomonic of COVID-19. Fetoplacental vascular changes and endothelial vacuolation associated with mild neonatal morbidity may suggest a possible transplacental impact on the fetus, to be further investigated.

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Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019–positive mothers and neonates at birth

Cited by 296 publications

References 6 publications

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

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.

Further placental pathology in mild COVID-19 of term pregnancy with pathophysiological correlates

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