Fetal and placental infection with SARS‐CoV‐2 in early pregnancy

Valdespino-Vázquez, María Yolotzin; Helguera-Repetto, Addy Cecilia; León-Juárez, Moisés; Villavicencio-Carrisoza, Oscar; Flores-Pliego, Arturo; Moreno-Verduzco, Elsa Romelia; Díaz-Pérez, Diana L.; Villegas-Mota, Isabel; Carrasco-Ramírez, Elba; López-Martı́nez, Irma; Giraldo-Gómez, David M.; Lira, Rosalía; Yocupicio-Monroy, Martha; Rodríguez-Bosch, Mario; Sevilla-Reyes, Edgar; Cortés-Bonilla, Manuel; Acevedo‐Gallegos, Sandra; Merchant‐Larios, Horacio; Cardona–Pérez, Jorge Arturo; Irles, Claudine

doi:10.1002/jmv.26965

Cited by 59 publications

(67 citation statements)

References 43 publications

(95 reference statements)

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“…Thorough literature search aimed at including all potentially relevant studies, multitude of histopathological anomalies and the large numbers of included cases 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 represent the main strengths of the present systematic review. The retrospective design of most of the included studies, small sample size, and heterogeneity in histopathological anomalies observed, are the main limitations of this systematic review.…”

Section: Discussionmentioning

confidence: 99%

“… 8 Several reports suggest an increased risk of placental lesions due to hypoperfusion and inflammation in women with SARS-CoV-2 infection. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 The potential association between SARS-CoV-2 and impaired placental function is crucial because it might lead to fetal decompensation and increased risk of perinatal mortality and morbidity. 66 , 67 Despite this, the occurrence of placental histopathological abnormalities in pregnancies complicated by SARS-CoV-2 infection is yet to be fully explored.…”

Section: Introductionmentioning

confidence: 99%

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Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis

Girolamo

Khalil

Alameddine

et al. 2021

American Journal of Obstetrics & Gynecology MFM

100

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Objectives : To report the spectrum of placental pathology findings in pregnancies complicated by SARS-CoV-2 infection. Methods : MEDLINE, EMBASE, Google Scholar and the Web of Science databases were searched up to August 11 th , 2021. Histopathological anomalies included maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), acute inflammatory pathology (AIP), chronic inflammatory pathology (CIP), increased perivillous fibrin and intervillous thrombosis. Sub-analyses including only symptomatic women and high-risk pregnancies were also performed. Histopathological analysis of the placenta included gross examination, histopathology on hematoxylin and eosin (H&E), immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), qRT-PCR on placental tissue, and transmission electron microscope (TEM). Random-effect meta-analyses were used to analyze the data. Results : Fifty-seven studies (1009 pregnancies) were included. MVM was reported in 31.4% (95% CI 21.0-42.8) of placentas, while FVM was observed in 26.9% of cases (95% CI 19.2-35.4). AIP and CIP were reported in 22.6% (95% CI 16.8-28.9) and 26.2% (95% CI 18.9-34.2) of cases, respectively. Increased perivillous fibrin was observed in 32.7% (95% CI 24.1-42.0) of placentas undergoing histopathological analysis, while intervillous thrombosis were observed in 14.6% (95% CI 10.6-21.8) of cases. Other placental findings, including either basal plate with attached myometrial fibers, microscopic accretism, villous edema, increased circulating nucleated Red Blood Cells or membranes with hemorrhage were reported in 38% (95% CI 28.5-48.0) of cases, while only 17.4% (95% CI 10.9-25.0) did not present any abnormal histological findings. Sub-analyses according to maternal symptoms due to SARS-CoV-2 infection or the presence of a high-risk pregnancy showed similar distribution of the different histopathological anomalies to that reported in the main analysis. The risk of placental histopathological anomalies was also higher when considering only case-control studies comparing women with SARS-CoV-2 infection with healthy controls. Conclusions : A significant proportion of placentas where SARS-CoV-2 occurred during pregnancy shows histopathological findings suggesting placental hypoperfusion and inflammation. Future multicenter prospective blinded studies are needed to correlate these placental lesions with pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis

Girolamo

Khalil

Alameddine

et al. 2021

American Journal of Obstetrics & Gynecology MFM

100

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“…This is in agreement with our results regarding the presence of changes in placental dysmaturity, vasculopathy, fibrinoid, chorangiosis, chorioamnionitis, hemorrhage, or infarction. In this sense, we have also observed such histopathological changes in the placenta of a first-trimester miscarriage, including active chronic intervillositis accompanied by Hofbauer cell inflammation and hyperplasia [ 6 ].…”

Section: Discussionmentioning

confidence: 98%

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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“…The SARS-CoV-2 nucleocapsid protein, viral RNA molecules in the placenta and fetal tissues were found, accompanied by RNA replication revealed by positive immunostaining against double-stranded RNA (dsRNA). In this study, the results indicate that congenital SARS-CoV-2 infection is possible in the first trimester of pregnancy and that fetal organs, such as the lungs and kidneys, are targeted by the coronavirus [ 152 ].…”

Section: Covid 19—placentamentioning

confidence: 99%

The Immunological Role of the Placenta in SARS-CoV-2 Infection—Viral Transmission, Immune Regulation, and Lactoferrin Activity

Bukowska-Ośko

Popiel

Kowalczyk

2021

IJMS

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A pandemic of acute respiratory infections, due to a new type of coronavirus, can cause Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) and has created the need for a better understanding of the clinical, epidemiological, and pathological features of COVID-19, especially in high-risk groups, such as pregnant women. Viral infections in pregnant women may have a much more severe course, and result in an increase in the rate of complications, including spontaneous abortion, stillbirth, and premature birth—which may cause long-term consequences in the offspring. In this review, we focus on the mother-fetal-placenta interface and its role in the potential transmission of SARS-CoV-2, including expression of viral receptors and proteases, placental pathology, and the presence of the virus in neonatal tissues and fluids. This review summarizes the current knowledge on the anti-viral activity of lactoferrin during viral infection in pregnant women, analyzes its role in the pathogenicity of pandemic virus particles, and describes the potential evidence for placental blocking/limiting of the transmission of the virus.

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Fetal and placental infection with SARS‐CoV‐2 in early pregnancy

Cited by 59 publications

References 43 publications

Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis

Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis

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

The Immunological Role of the Placenta in SARS-CoV-2 Infection—Viral Transmission, Immune Regulation, and Lactoferrin Activity

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