The Effects of COVID-19 on the Placenta During Pregnancy

Rad, Habib Sadeghi; Röhl, Joan; Stylianou, Nataly; Allenby, Mark C.; Bazaz, Sajad Razavi; Warkiani, Majid E.; Guimarães, Fernando; Clifton, Vicki L.; Kulasinghe, Arutha

doi:10.3389/fimmu.2021.743022

Cited by 52 publications

(49 citation statements)

References 131 publications

(136 reference statements)

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“…This finding is of importance not only in this model of PE, but also during human PE where levels of Gas6 have been found to be increased in the plasma of the preeclamptic mother [ 6 ]. Although studies of lungs during PE are scarce, recent reports have shown that pregnant women infected by the virus COVID-19 (which mostly affects the lungs) have increased lung inflammation and this correlates with obstetric complications such as miscarriages, restricted fetal growth, and most relevant to our studies, the development of PE-like symptoms [ 48 , 49 , 50 ]. This also correlates with increased serum Gas6 and increased lung AXL in patients affected by this virus [ 51 ].…”

Section: Discussionmentioning

confidence: 95%

Lung Inflammation Is Associated with Preeclampsia Development in the Rat

Curtis

Clarke

Hanegan

et al. 2022

Cells

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Preeclampsia (PE) is an obstetric complication associated with significant health implications for the fetus and mother. Studies have shown a correlation between lung disease development and PE. Gas6 protein is expressed in the lung and placenta, and binds to the AXL Tyrosine kinase receptor. Recently, our laboratory utilized Gas6 to induce preeclamptic-like conditions in rats. Our objective was to determine the role of Gas6/AXL signaling in the maternal lung during PE development. Briefly, pregnant rats were divided into control, Gas6, or Gas6 + R428 (an AXL inhibitor). Immunofluorescence was performed to determine AXL expression. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cell secretion. Western blot was performed to detect signaling molecules and ELISA determined inflammatory cytokines. We observed increased proteinuria and increased blood pressure in Gas6-treated animals. AXL was increased in the lungs of the treated animals and BALF fluid revealed elevated total protein abundance in Gas6 animals. Extracellular-signal regulated kinase (ERK) and protein kinase B (AKT) signaling in the lung appeared to be mediated by Gas6 as well as the secretion of inflammatory cytokines. We conclude that Gas6 signaling is capable of inducing PE and that this is associated with increased lung inflammation.

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Section: Discussionmentioning

confidence: 95%

Lung Inflammation Is Associated with Preeclampsia Development in the Rat

Curtis

Clarke

Hanegan

et al. 2022

Cells

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“…Examination of placentas infected with SARS-CoV-2 from stillborn fetuses has been enlightening, significantly adding to the understanding of the mechanism(s) for intrauterine fetal demise. These studies have largely been made possible by the development of techniques for the tissue localization of SARS-CoV-2 in the placenta including immunohistochemistry to detect viral antigens and RNA in situ hybridization to identify viral nucleic acid [ 25 , 42 , 77 ] ( Figure 6 ). Unfortunately, in the large majority of these cases the specific strain of SARS-CoV-2 was not identified.…”

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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“…These changes can cause a difference in the maternal immune response to infections during pregnancy, particularly to SARS-CoV-2 [ 2 ]. During gestation, maternal levels of natural killer (NK) cells decrease [ 3 ]. NK cells are innate immune cells that are known to have cytotoxic activity against virally infected cells.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the pregnant woman’s ability to protect herself from viral infections is attenuated. Additionally, NK cells are reduced during infection with SARS-CoV-2 infection [ 3 ]. As a result, a COVID-19-positive gravid patient is at risk for acquiring additional respiratory viral infections.…”

Section: Introductionmentioning

confidence: 99%

“…As a result, a COVID-19-positive gravid patient is at risk for acquiring additional respiratory viral infections. Additionally, during pregnancy, the maternal immune system prioritizes humoral immune responses over cellular responses, with the CD4+ T cell population being Th2 phenotypes rather than Th1 phenotypes [ 3 ]. This is especially important considering patients with severe outcomes of COVID-19 also displayed reduced numbers of adaptive immune cells relative to those who did not experience severe outcomes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Cardiac Arrest and Hypoxic-Ischemic Encephalopathy Following an Emergency Caesarean Section in a COVID-19 Patient

Palati¹,

Sanchez²,

Campbell³

2022

Cureus

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While young, healthy individuals without underlying medical conditions have generally not suffered catastrophic health consequences from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), gravid patients appear to be at much higher risk of complications from this virus. A 29-year-old G3P2 patient at 30 weeks and three days presented with worsening dyspnea and chest pain after testing positive for coronavirus disease 2019 (COVID-19) infection two days prior. Notably, she had not received COVID-19 vaccination. A non-reassuring fetal tracing and fetal bradycardia were discovered on routine prenatal monitoring during admission, and an urgent caesarean section was performed. She subsequently required supplemental oxygen due to respiratory distress and remained hospitalized. She clinically deteriorated from a respiratory standpoint. Several days later, she experienced cardiac arrest with a return of spontaneous circulation (ROSC) in nine minutes. While the baby was discharged home and is doing well, the patient, unfortunately, expired from hypoxic encephalopathy secondary to COVID-19 pneumonia and complications of cardiorespiratory arrest. This case highlights the severe sequelae of COVID-19 infection in a postpartum patient, including ventilator-dependent respiratory failure, sudden cardiac death, hypoxic encephalopathy, and coma.

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The Effects of COVID-19 on the Placenta During Pregnancy

Cited by 52 publications

References 131 publications

Lung Inflammation Is Associated with Preeclampsia Development in the Rat

Lung Inflammation Is Associated with Preeclampsia Development in the Rat

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

Cardiac Arrest and Hypoxic-Ischemic Encephalopathy Following an Emergency Caesarean Section in a COVID-19 Patient

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