Severe SARS-CoV-2 placenta infection can impact neonatal outcome in the absence of vertical transmission

Cribiù, Fulvia Milena; Erra, Roberta; Pugni, Lorenza; Rubio-Pérez, Carlota; Alonso, Lidia; Simonetti, Sara; Croci, Giorgio Alberto; Serna, Garazi; Ronchi, Andrea; Pietrasanta, Carlo; Lunghi, G.; Fagnani, Anna Maria; Piñana, María; Matter, Matthias S.; Tzankov, Alexandar; Terracciano, Luigi; Antón, Andrés; Ferrazzi, E.; Ferrero, Stefano; Iurlaro, Enrico; Seoane, Joan; Nuciforo, Paolo

doi:10.1172/jci145427

Cited by 74 publications

(96 citation statements)

References 28 publications

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“…This translates into a reduced capacity of the fetoplacental unit to adapt to episodes of reduced placental blood flow, for instance during uterine contractions. This supports the hypothesis that the increased risk of foetal compromise is not related to vertical transmission but due to functional impairment of the placenta caused by severe placental infection as was recently described [ 45 ]. Lower birthweight, Apgar score and pH in active COVID-19 cases add further evidence that COVID-19 increases the risk of foetal compromise.…”

Section: Discussionsupporting

confidence: 90%

Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms

Husen

Meeren

Verdijk

et al. 2021

Viruses

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Background: Although the risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. Methods: A prospective, longitudinal, multicentre, cohort study. All pregnant women presenting between April 2020 and March 2021 with a nasopharyngeal RT-PCR-confirmed SARS-CoV-2 infection were included. Around delivery, maternal, foetal and placental PCR samples were collected. Placental pathology was correlated with clinical maternal characteristics of COVID-19. Results: Thirty-six patients were included, 33 singleton pregnancies (n = 33, 92%) and three twin pregnancies (n = 3, 8%). Twenty-four (62%) placentas showed at least one abnormality. Four placentas (4/39, 10%) showed placental staining positive for the presence of SARS-CoV-2 accompanied by a unique combination of diffuse, severe inflammatory placental changes with massive perivillous fibrin depositions, necrosis of syncytiotrophoblast, diffuse chronic intervillositis, and a specific, unprecedented CD20+ B-cell infiltration. This SARS-CoV-2 placental signature seems to correlate with foetal distress (75% vs. 15.6%, p = 0·007) but not with the severity of maternal COVID-19 disease. Conclusion: We describe a unique placental signature in pregnant patients with COVID-19, which has not been reported in a historical cohort. We show that the foetal environment can be seriously compromised by disruption of placental function due to local, devastating SARS-CoV-2 infection. Maternal clinical symptoms did not predict the severity of the SARS-CoV-2-related placental signature, resulting in a lack of adequate identification of maternal criteria for pregnancies at risk. Close foetal monitoring and pregnancy termination in case of foetal distress can prevent adverse pregnancy outcomes due to COVID-19 related placental disease.

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Section: Discussionsupporting

confidence: 90%

Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms

Husen

Meeren

Verdijk

et al. 2021

Viruses

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“…Our results are in agreement with numerous reports showing that SARS-CoV-2 is undetected in the placenta 24,100,101 , amniotic fluid 102-104 , and neonates 5,24,29,102,103 . Yet, SARS-CoV-2 has been reported in the placentas of severe COVID-19 patients 15,16,23,27,105 , indicating that this virus can on rare occasions reach and infect this organ. Therefore, the absence of SARS-CoV-2 in the chorioamniotic membranes, placental villi, and basal plate of our mostly asymptomatic study population is in accordance with the known scarcity of placental infection 106 .…”

Section: Discussionmentioning

confidence: 99%

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

Garcia‐Flores

Romero

et al. 2021

Preprint

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Pregnant women are a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Herein, we report that SARS-CoV-2 infection during pregnancy primarily induced specific maternal inflammatory responses in the circulation and at the maternal-fetal interface, the latter being governed by T cells and macrophages. SARS-CoV-2 infection during pregnancy was also associated with a cytokine response in the fetal circulation (i.e. umbilical cord blood) without compromising the cellular immune repertoire. Moreover, SARS-CoV-2 infection neither altered fetal cellular immune responses in the placenta nor induced elevated cord blood levels of IgM. Importantly, SARS-CoV-2 was not detected in the placental tissues, nor was the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and further emphasizes the rarity of placental infection.

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“…Consistent with a low frequency presence of SARS-CoV-2 in the placenta [22], vertical transmission is rather infrequent [21]: a systematic review reported a rate of 3.2% vertical transmission in mothers who tested positive for SARS-CoV-2 (diagnosed by RT-PCR) during the third trimester of pregnancy [22]. A recent study of placentas taken from COVID-19 positive mothers [23] describes a low-level presence of RNA in about half of placentas. No substantial histopathological, maternal, or neonatal outcome features were detected associated with this low level of viral RNA.…”

Section: Introductionmentioning

confidence: 89%

High viral SARS-CoV-2 load in placenta of patients with hypertensive disorders after COVID-19 during pregnancy

Fabre¹,

Calvo

Ruiz

et al. 2021

Preprint

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Introduction: Studies described an increased frequency of hypertensive disorders of pregnancy after a COVID-19 episode. There is limited evidence about SARS-CoV-2 viral load in placenta. This study aimed to investigate the relationship between SARS-CoV-2 viral load in placenta and clinical development of HDP after COVID-19 throughout different periods of gestation. Methods: This was a case-control study in women with and without gestational hypertensive disorders (HDP) after SARS-CoV-2 infection diagnosed by RT-PCR during pregnancy. Patients were matched by gestational age at the moment of COVID-19 diagnosis. We performed an analysis of SARS-CoV-2 RNA levels in placenta. Results: A total of 28 women were enrolled. Sixteen patients were diagnosed with COVID-19 during the third trimester and the remaining twelve patients in the others trimesters. Ten placentas (35.7%) were positive for SARS-CoV-2, nine of them (90%) belonged to the HDP group versus one (10%) in control group (p=0.009). Those cases with the highest loads of viral RNA developed severe-preeclampsia. Conclusion: The presence of SARS-CoV-2 was more frequent in placentas of patients with HDP after COVID-19. There seems to be a relationship between high viral load in the placenta and the development of hypertensive disorders. We found SARS-CoV-2 viral load in placenta after birth in mothers infected at the first half of pregnancy, but with negative nasopharyngeal RT-PCR at delivery. Our data suggest that SARS-CoV-2 infection during pregnancy could trigger gestational hypertensive disorders through placenta-related mechanisms.

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Severe SARS-CoV-2 placenta infection can impact neonatal outcome in the absence of vertical transmission

Cited by 74 publications

References 28 publications

Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms

Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

High viral SARS-CoV-2 load in placenta of patients with hypertensive disorders after COVID-19 during pregnancy

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