Stillbirth and fetal capillary infection by SARS-CoV-2

Gioia, Cira Di; Zullo, Fabrizio; Vecchio, Roberta Costanza Bruno; Pajno, Cristina; Perrone, Giuseppina; Gabriela, Paola; Pecorini, Francesco; Mascio, Daniele Di; Carletti, Raffaella; Prezioso, Carla; Pietropaolo, Valeria; Masuelli, Laura; Bei, Roberto; Ciallella, Costantino; Rocca, Carlo Della; Giancotti, Antonella; Brunelli, Roberto

doi:10.1016/j.ajogmf.2021.100523

Cited by 21 publications

(16 citation statements)

References 8 publications

(4 reference statements)

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“…In pregnant women, the specific clinical manifestation of SARS-CoV-2 infection remains unclear [19]. Only sporadic cases of vertical transmission were previously described [22]. Identifying molecular changes occurring in the maternal-fetal interface in pregnant women with COVID-19 represents a major challenge.…”

Section: Resultsmentioning

confidence: 99%

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta

Gabanella

Barbato

Corbi

et al. 2022

IJMS

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The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal–fetal interface.

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Section: Resultsmentioning

confidence: 99%

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta

Gabanella

Barbato

Corbi

et al. 2022

IJMS

Self Cite

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“…Our data from these 68 cases support previous case reports suggesting that placental insufficiency is responsible for perinatal deaths occurring with SARS-CoV-2 placentitis. 58,[91][92][93][94][95][96][97] In summary, we found that SARS-CoV-2 placentitis can cause extensive placental damage as a result of destructive lesions, and that the damage can be further exacerbated by additional pathology abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

Schwartz¹,

Avvad-Portari

Babál

et al. 2022

Archives of Pathology &Amp; Laboratory Medicine

155

142

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Context.— Perinatal death is an increasingly important problem as the COVID-19 pandemic continues, but the mechanism of death has been unclear. Objective.— To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for SARS-CoV-2. Design.— Case-based retrospective clinico-pathological analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.— All 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis, the three findings constituting SARS-CoV-2 placentitis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25/68) and chronic villitis (32%; 22/68). The majority (19, 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.— The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.

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“…Extensive intervillous fibrin deposition, involving up to 70% or more of the placental tissues in one case, was present in the placentas from all 5 fetuses. Following this report, additional case reports of the placental pathology from stillborn fetuses delivered to mothers with COVID-19 were reported that showed all the placentas to be markedly abnormal and extensively involved with similar destructive features–increased or massive intervillous fibrin deposition, villous trophoblast necrosis, and chronic histiocytic intervillositis [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. In their report of a stillbirth from a mother having COVID-19 at 30 weeks 4 days gestation in Bratislava, Biringer et al [ 80 ] believed the cause of death to be acute placental insufficiency based upon their findings of placental destruction due to SARS-CoV-2 placentitis and an autopsy revealing fetal organs to have no morphological abnormalities.…”

Section: Covid-19 Infection and Stillbirthmentioning

confidence: 97%

“…In their report of a stillbirth from a mother having COVID-19 at 30 weeks 4 days gestation in Bratislava, Biringer et al [ 80 ] believed the cause of death to be acute placental insufficiency based upon their findings of placental destruction due to SARS-CoV-2 placentitis and an autopsy revealing fetal organs to have no morphological abnormalities. In another case of probable placental insufficiency causing stillbirth, di Gioia et al [ 79 ] described a mother with COVID-19 from Rome who had a stillborn fetus at 36 weeks and 1 day of gestation. The placenta demonstrated extensive involvement by regions of hemorrhagic or ischemic necrosis with central and peripheral villous infarctions, and thrombosis of several fetal and maternal vessels with luminal fibrin and platelet depositions.…”

Section: Covid-19 Infection and Stillbirthmentioning

confidence: 99%

Stillbirth after COVID-19 in Unvaccinated Mothers Can Result from SARS-CoV-2 Placentitis, Placental Insufficiency, and Hypoxic Ischemic Fetal Demise, Not Direct Fetal Infection: Potential Role of Maternal Vaccination in Pregnancy

Schwartz

2022

Viruses

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Stillbirth is a recently recognized complication of COVID-19 in pregnant women. Other congenitally transmitted infections from viruses, bacteria and parasites can cause stillbirth by infecting fetal organs following transplacental transmission of the agent from the maternal bloodstream. However, recent research on pregnant women with COVID-19 having stillbirths indicates that there is another mechanism of stillbirth that can occur in placentas infected with SARS-CoV-2. In these cases, viral infection of the placenta results in SARS-CoV-2 placentitis, a combination of concurrent destructive findings that include increased fibrin deposition which typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis and trophoblast necrosis. These three pathological lesions, in some cases together with placental hemorrhage, thrombohematomas and villitis, result in severe and diffuse placental parenchymal destruction. This pathology can involve greater than one-half of the placental volume, averaging 77% in the largest study of 68 cases, effectively rendering the placenta incapable of performing its function of oxygenating the fetus. This destructive placental process can lead to stillbirth and neonatal death via malperfusion and placental insufficiency which is independent of fetal infection. Fetal autopsies show no evidence that direct infection of fetal organs is contributory. Because all mothers examined have been unvaccinated, maternal vaccination may prevent viremia and consequent placental infection.

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Stillbirth and fetal capillary infection by SARS-CoV-2

Cited by 21 publications

References 8 publications

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta

Exploring Mitochondrial Localization of SARS-CoV-2 RNA by Padlock Assay: A Pilot Study in Human Placenta

Placental Tissue Destruction and Insufficiency From COVID-19 Causes Stillbirth and Neonatal Death From Hypoxic-Ischemic Injury

Stillbirth after COVID-19 in Unvaccinated Mothers Can Result from SARS-CoV-2 Placentitis, Placental Insufficiency, and Hypoxic Ischemic Fetal Demise, Not Direct Fetal Infection: Potential Role of Maternal Vaccination in Pregnancy

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