Pandemic stress and SARS-CoV-2 infection are associated with pathological changes at the maternal-fetal interface.

INTRODUCTION: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology. METHODS: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded. RESULTS: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index. DISCUSSION: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.

Third trimester stillbirth during the first wave of the SARS-CoV-2 pandemic: Similar rates with increase in placental vasculopathic pathology.

Whether early SARS-CoV-2 definitively increases the risk of stillbirth is unknown, though studies have suggested possible trends of stillbirth increase during the pandemic. This study of third trimester stillbirth does not identify an increase in rates during the first wave of the pandemic period, however investigation of the placental pathology demonstrates trends towards more vascular placental abnormalities.

Placental lesions and SARS-Cov-2 infection: Diffuse placenta damage associated to poor fetal outcome.

INTRODUCTION: Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. METHOD: We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. RESULTS: We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers' infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. DISCUSSION: SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.

COVID-19 and pregnancy: clinical case of critical presentation, placental inflammation and demonstrated fetal vertical transmission / COVID-19 y embarazo: caso clínico de presentación crítica, inflamación placentaria y transmisión vertical fetal demostrada

ANTECEDENTES: La pandemia global de COVID-19 llega al continente americano en marzo del año 2020 y en menos de dos meses reúne a más de la mitad de los casos a nivel global. OBJETIVO: Caso clínico de una mujer embarazada con una presentación crítica de COVID-19 y embarazo a las 25 semanas de gestación, en el contexto del peak de la pandemia en Chile en el otoño del año 2020. CASO CLÍNICO: El 20 de junio de 2020, una mujer de 34 años, con 25 semanas de embarazo, es trasladada desde Hospital de San Bernardo a Clínica Las Condes en Santiago, Chile, con un cuadro de 10 días de evolución de COVID-19, que evoluciona a una situación crítica con insuficiencia respiratoria severa. Ingresa a unidad de cuidados intensivos para ventilación mecánica. Las imágenes de radiología simple y de tomografía axial computarizada de tórax demuestran una neumopatía bilateral con imágenes características opacidades en vidrio esmerilado, asociado a engrosamiento intersticial, imágenes descritas previamente como características para COVID-19. La paciente permanece en unidad de cuidados intensivos en ventilación mecánica por siete días, con evolución favorable posterior, mejoría del cuadro séptico y alta después de 22 días de hospitalización. El parto ocurre en forma espontánea a las 38 semanas, la madre y el recién nacido evolucionan en buen estado general. El examen histopatológico placentario demuestra compromiso inflamatorio vellositario y los exámenes de anticuerpos en sangre del recién nacido demuestran la presencia de anticuerpos del tipo IgG e IgM. Se trata de uno de los pocos casos demostrados reportados de transmisión transplacentaria vía sanguínea de SARS-CoV-2 de la madre al recién nacido.

BACKGROUND: The global COVID-19 pandemic reaches the American continent in March 2020 and in less than two months it brings together more than half of the cases globally.OBJECTIVE: The clinical case of a 25-week pregnant woman with a critical presentation of COVID-19 and pregnancy at 25 weeks of gestation, is presented in the context of the peak of the pandemic in Chile in the fall of 2020. CLINICAL CASE: On June 20, 2020, a 34-year-old woman, 25 weeks pregnant, is transferred from Hospital de San Bernardo to Clinica Las Condes in Santiago, Chile, with a ten-day evolution of a COVID-19 that evolves to critical with severe respiratory failure. She is admitted to the intensive care unit for mechanical ventilation. Chest computerized axial tomography images demonstrate bilateral pneumopathy with characteristic images of ground-glass opacities, associated with interstitial thickening, images previously described as characteristics for COVID-19. The patient remains in the intensive care unit on mechanical ventilation for seven days, with subsequent favorable evolution, improvement of the septic condition, and discharge after 22 days of hospitalization. Delivery occurs at 38 weeks, the mother and the newborn evolve in good general condition. The placental histopathological examination demonstrates villous inflammatory involvement, and the newborn's blood tests show the presence of IgG and IgM antibodies. It is one of the few reported cases of transplacental transmission of SARS-CoV-2 from the mother to the newborn.

COVID-19 as an independent risk factor for subclinical placental dysfunction.

BACKGROUND: The pandemic of the severe acute respiratory distress syndrome-associated Coronavirus-2 (SARS-CoV-2) has affected millions around the world. In pregnancy the dangers to the mother and fetus are still being explored. SARS-CoV2 can potentially compromise maternal and neonatal outcomes and this may be dependent on the pregnancy stage during which the infection occurs. OBJECTIVE: The present study was done to find the histopathological alterations in the placenta of SARS-CoV-2 positive pregnancies with either no symptoms or mild coronavirus disease (COVID)-19 related symptoms and its association with neonatal outcomes. STUDY DESIGN: This was a prospective analytical study. Twenty seven asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women with a singleton pregnancy delivered between 1st July 2020 and 15th September 2020, were included as cases. An equal number of SARS-CoV-2 negative singleton pregnancies matched for maternal and gestational age during the same period were included as controls. After delivery the histopathological examination of the placenta of these women was done and the findings recorded on a predesigned proforma based on the Amsterdam consensus criteria for evidence of maternal and fetal vascular malperfusion changes. RESULTS: The baseline characteristics were comparable between the cases and controls. The following features of maternal vascular malperfusion (MVM) were significantly higher in the placentae of COVID-19 positive pregnancies: retroplacental hematomas (RPH), accelerated villous maturation (AVM), distal villous hyperplasia (DVH), atherosis, fibrinoid necrosis, mural hypertrophy of membrane arterioles (MHMA), vessel ectasia and persistence of intramural endovascular trophoblast (PIEVT). Fetal vascular malperfusion (FVM) significantly associated with the positive pregnancies were chorioangiosis, thrombosis of the fetal chorionic plate (TFCP), intramural fibrin deposition (IMFD) and vascular ectasia. Additionally, perivillous fibrin deposition was also significantly higher in the placentae of cases. The percentage of spontaneously delivered women was comparable in the two groups. The sex and weight of the newborn and the number of live births were comparable between the two groups. CONCLUSIONS: Asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women, with otherwise uncomplicated pregnancies, show evidence of placental injury at a microscopic level. Similar findings have been demonstrated in other studies too. This placental injury apparently does not lead to poor pregnancy outcomes. The extent of this injury in symptomatic cases of COVID-19 pregnancies and its consequences on the outcomes need to be analysed.

Maternal and neonatal response to COVID-19.

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to maternal and newborn health has yet to be determined. Several reports suggest pregnancy does not typically increase the severity of maternal disease; however, cases of preeclampsia and preterm birth have been infrequently reported. Reports of placental infection and vertical transmission are rare. Interestingly, despite lack of SARS-CoV-2 placenta infection, there are several reports of significant abnormalities in placenta morphology. Continued research on pregnant women infected with SARS-CoV-2 and their offspring is vitally important.

Placental Pathology in Covid-19 Positive Mothers: Preliminary Findings.

This study describes the pathology and clinical information on 20 placentas whose mother tested positive for the novel Coronovirus (2019-nCoV) cases. Ten of the 20 cases showed some evidence of fetal vascular malperfusion or fetal vascular thrombosis. The significance of these findings is unclear and needs further study.