Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features

Rebutini, Patricia Zadorosnei; Zanchettin, Aline Cristina; Stonoga, Emanuele Therezinha Schueda; Prá, Daniele Margarita Marani; Oliveira, André Luiz Parmegiani de; Dezidério, Felipe da Silva; Fonseca, Aline Simoneti; D’Agostini, Júlio César Honório; Hlatchuk, Elisa Carolina; Furuie, Isabella Naomi; Longo, Jessica da Silva; Cavalli, Bárbara Maria; Dino, Carolina Lumi Tanaka; Dias, Viviane Maria de Carvalho Hessel; Percicote, Ana Paula; Nogueira, Meri Bordignon; Raboni, Sônia Mara; Carvalho, Newton Sérgio de; Machado-Souza, Cleber; Noronha, Lúcia de

doi:10.3389/fimmu.2021.685919

Cited by 47 publications

(71 citation statements)

References 61 publications

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“…Our study confirmed that a high maternal inflammatory state is possibly contributing to placental insufficiency. As previously stated, we also found that the frequency of placental abnormalities is correlated with the severity of disease [ 49 ]. Although we did not detect SARS-CoV-2 Spike protein in any of the placentas, vertical transmission can still be possible in some cases.…”

Section: Discussionsupporting

confidence: 78%

“…In line with our study, a recent study found that the deficiency in spiral remodeling was more common in women with SARS-CoV-2 infection than healthy controls. Additionally, the rate of fetal vascular thrombosis was higher in placentas of SARS-CoV-2 infected pregnant compared with healthy controls [ 49 ]. There is emerging evidence that severe SARS-CoV-2 infection is prone to an exaggerated inflammatory response, defined as a cytokine storm [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

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Placental deficiency during maternal SARS-CoV-2 infection

et al. 2022

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Introduction Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. Methods This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. Results The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. Discussion The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Placental deficiency during maternal SARS-CoV-2 infection

et al. 2022

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“…Whilst there are reports of an increased risk of stillbirth (18,19), other studies have reported no difference (20,21). There have been reports of an increase in neonatal deaths (7,19); however, in our study, there were no poor pregnancy outcomes, although this is partly by design as women with Active COVID and a poor pregnancy outcome (e.g., a prior fetal death) were not approached to take part in the study.…”

Section: Poor Pregnancy Outcomes and Placental Pathologycontrasting

confidence: 60%

“…There are conflicting data available as to whether the number of Hofbauer cells are increased following maternal SARS-CoV-2 infection. Whilst some studies have found no increase in Hofbauer cell number (7,8), other studies report an increase (9). There are limited data regarding the effect of SARS-CoV-2 infection on T or B lymphocyte numbers, although one study reported no difference following maternal infection (8).…”

Section: Introductionmentioning

confidence: 99%

Placental Macrophages Following Maternal SARS-CoV-2 Infection in Relation to Placental Pathology

Sharps¹,

Garrod²,

Aneni³

et al. 2022

Front.Virol.

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IntroductionIn December 2019, a novel coronavirus, SARS-CoV-2, was identified. Whilst pregnant women appear to be at risk of severe infection, pre-term birth, and stillbirth, it is unclear whether placental dysfunction is a consistent feature of maternal SARS-CoV-2 infection during pregnancy. We aim to describe the immune response in placentas of women who had COVID-19 infection during pregnancy and investigate whether there are any associated morphological changes.MethodsThe placentas of women testing positive for COVID-19 during their pregnancy were compared to contemporaneous controls who were not known to have had COVID-19 during pregnancy. Samples of each placenta were sent for histopathological analysis or underwent immunohistochemical staining for CD163, CD20, CD3, CD31, and SARS-CoV-2 spike protein. A subset of samples were sent for transmission electron microscopy.ResultsThere was a significant increase in the number of CD163+ macrophages in the Post COVID group (p = 0.0020). There was no difference in the percentage of CD3+, CD20+ cells, but there was an increase in placental vascularity in the Post COVID group compared to controls (p = 0.026).There were no structural differences observed between the samples sent for EM analysis. However, one of the placentas from the Post COVID group was seen to have several large sub-apical vacuoles in the syncytiotrophoblast. We did not observe any virions within the vacuoles and SARS-CoV-2 spike protein staining was negative for the sample. Histopathological investigations indicated that there was no specific placental pathology caused by maternal COVID-19 infection in this cohort of samples.ConclusionsThis study did not confirm previous studies which describe a possible increase in cases of both maternal and fetal vascular malperfusion, and placentitis in women who had COVID-19, which were seen in association with adverse pregnancy outcomes. It remains unclear whether observed abnormalities are caused by maternal infection, or whether maternal infection exacerbates existing placental pathology; understanding why some placentas generate these abnormalities is a key goal.

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“…Moreover, 90% of asymptomatic women with C T values less than 25 developed placental fibrinoid compared to no differences in C T values in symptomatic patients. On this matter, Rebutini et al found accentuated but non-significant fibrin deposition in placentas of COVID19 positive women compared to non-COVID19 patients [ 23 ]. This is somewhat similar to our findings.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Infection in Pregnancy: PCR Cycle Thresholds, Placental Pathology, and Perinatal Outcomes

Laresgoiti-Servitje

Cardona–Pérez

Hernández-Cruz

et al. 2021

Viruses

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(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.

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Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features

Cited by 47 publications

References 61 publications

Placental deficiency during maternal SARS-CoV-2 infection

Placental deficiency during maternal SARS-CoV-2 infection

Placental Macrophages Following Maternal SARS-CoV-2 Infection in Relation to Placental Pathology

COVID-19 Infection in Pregnancy: PCR Cycle Thresholds, Placental Pathology, and Perinatal Outcomes

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