COVID-19 during the Third Semester of Pregnancy: Maternal Characteristic, Possibility of Intrauterine Transmission and Neonatal Outcome in Aceh, Indonesia

BACKGROUND: Pregnant women are vulnerable against COVID-19 infection due to physiological and immunological changes. COVID-19 in pregnancy affects fetal well-being with a potential for vertical infection. AIM: This study aims to determine the incidence of vertical infection and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants born to mothers with positive COVID-19 infection. MATERIALS AND METHODS: Amniotic fluid, swabs of the newborn's nasopharynx and oropharynx, and swabs of the placenta were examined using reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2. Serological examination was performed by Electro-Chemiluminescence Immunoassay on infant's blood. RESULT(S): Four of 33 pregnant women gave birth to infants positive SARS-CoV-2 infection. RT-PCR examination of all amniotic fluid and placental swabs was negative for SARS-CoV-2. Four of 33 infants (12.1%) showed negative polymerase chain reaction (PCR) results but positive SARS-CoV-2 antibodies, another 4 newborns (12.1%) showed positive PCR results, but no SARS-CoV-2 antibodies detected. The remaining 25 babies (75.8%) showed both negative PCR and serologic results. CONCLUSION(S): No evidence of vertical transmission found in this study.Copyright © 2023 Cut Meurah Yeni, Zinatul Hayati, Sarjani M. Ali, Hasanuddin Hasanuddin, Rusnaidi Rusnaidi, Cut Rika Maharani.

Covid-19: Is the placenta a safe space

Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.

The immunopathology of COVID-19 placentitis: A multi-omic spatial approach

Problem: COVID-19 placentitis is a rare complication of maternal SARS-CoV-2 respiratory infection associated with serious adverse obstetric outcomes, including intra-uterine death. The precise role of SARS-CoV-2 in COVID-19 placentitis is uncertain, as trophoblast infection is only observed in around one-half of the affected placenta. Method of Study: Through multi-omic spatial profiling, including Nanostring GeoMX digital spatial profiling and Lunaphore COMET multiplex IHC, we provide a deep characterization of the immunopathology of placentitis from obstetrically complicated maternal COVID-19 infection. Result(s):We show that SARS-CoV-2 infection of placental trophoblasts is associated with a distinct innate and adaptive immune cell infiltrate, florid cytokine expression and upregulation of viral restriction factors. Quantitative spatial analyses reveal a unique microenvironment surrounding virus-infected trophoblasts characterizedd by multiple immune evasion mechanisms, including immune checkpoint expression, cytotoxic T-cell exclusion, and interferon blunting. Placental viral loads inversely correlated with the duration of maternal infection consistent with progressive virus clearance, potentially explaining the absence of virus in some cases. Conclusion(s): Our results demonstrate a central role for placental SARS-CoV-2 infection in driving the unique immunopathology of COVID-19 placentitis.

COVID-19 Infection and Vaccination in Pregnancy: What Do We Know Now?

SARS-CoV-2 infection during pregnancy has significant implications for both mothers and their offspring. Pregnant individuals are more likely to progress to severe or critical COVID-19 than nonpregnant reproductiveaged women. Similarly, COVID-19 is associated with a number of pregnancy complications including preterm birth, hypertensive disorders of pregnancy, and cesarean delivery. These adverse outcomes and the morbidity for pregnant people with COVID-19 are closely linked to the severity of COVID-19, and the variant of SARS-CoV-2. Recent data demonstrate that the worst maternal and fetal outcomes were present during the time period of the Delta variant of SARS-CoV-2. Specifically, there was an increase in stillbirth observed in association mostly with the Delta variant due to placental damage, and a greater risk of intensive care unit admission when compared to time periods when other non-Delta strains were predominant. Like other populations, pregnant individuals with other comorbidities such as obesity and chronic hypertension are at increased risk of more severe disease. Early in the pandemic, pregnant patients were much less likely than the general population to be vaccinated, due to a lack of data for vaccine efficacy and safety in pregnancy. As reassuring data have emerged, the vaccination rate of the pregnant population has increased, resulting in decreased disease severity and improved maternal outcomes. Vaccination also has beneficial implications for early neonatal health. The long-term implications of SARSCoV- 2 infection during pregnancy for both mothers and their children remain largely unknown and are a subject of ongoing investigation.

Perinatal aspects of sars-cov-2 infection during pregnancy: A potential cause for concern

Ever since the beginning of COVID-19 pandemic, uncertainty regarding clinical presentation and differences among various subpopulations exist. With more than 209,870,000 confirmed cases and more than 4,400,000 deaths worldwide, we are facing the new era of health crisis which will undoubtedly impair global health, economic and social circumstances. In the past year, numerous genetic mutations which code SARS-CoV-2 proteins led to the occurrence of new viral strains, with higher transmission rates. Apart from the implementation of vaccination, the effect of SARS-CoV-2 on pregnancy outcome and maternal fetal transmission remains an important concern. Although neonates diagnosed with COVID-19 were mostly asymptomatic or presented with mild disease, the effect on early pregnancy is yet to be evident. While positive finding of SARS-CoV-2 RNA in some samples such as amniotic fluid, placental tissue, cord blood and breast milk exists, additional research should confirm its association with transplacental transmission.Copyright © 2022, Dr. Mladen Stojanovic University Hospital. All rights reserved.

Determination of the Effects of Prenatal Remdesivir Exposure on Placenta Morphology, Placental IgG Transfer, and Fetal Growth in a Humanized Mouse Model

Remdesivir (RDV) is an antiviral medication used most recently for the treatment of COVID-19. Although no adverse effects were observed on perinatal parameters in reproductive and development toxicology studies at doses up to four-fold clinical area under the curve (AUC) exposures, some researchers have reported that therapeutic levels of RDV may impair early embryogenesis, as observed by in vitro studies. In addition, the influence of prenatal RDV exposure on maternal IgG transfer in the placenta is still unknown. Administration of RDV in pregnant humanized mouse model (Tg32), which expresses the human Fc gamma receptor and transporter (FCGRT) gene, was used to further evaluate potential effects on IgG transfer and concurrent perinatal endpoints. Animals were dosed daily from gestational days (GDs) 10- 14 with 25 mg/kg RDV (GS-5734) via intravenous injection (n=3-5 per group). Concurrent vehicle control animals were dosed intravenously with 12% sulfobutyl ether- beta-cyclodextrin in water (pH3.5;NaOH/HCl). All animals were administered 2 mg/kg human IgG via intravenous injection on GD 14. Placentae and fetuses were collected from dams on GD 14, 15, 16, and 18 and evaluated using histopathology and qPCR for inflammation markers. No abnormal morphologies (necrosis/apoptosis) of placentae were observed between the concurrent control and RDVdosed groups. Additionally, no differences in maternal body weights were observed. There were no statistically significant differences in placenta weights. There were no statistically significant changes in pregnancy parameters (implantation sites and dead fetuses/litter) and fetal weights between the RDV-dosed group and concurrent controls at GD 14, 15, 16, and 18. No changes were observed in transcript levels of inflammation markers in the RDV-dosed group when compared to the concurrent control group. There was a slightly lower ratio of fetal IgG level to maternal IgG levels in the RDV-dosed group;however, no statistically significant differences were observed between the RDV-dosed group and concurrent controls on GD 14, 15, 16, and 18. Our results suggest that a daily dose of 25 mg/kg RDV on GDs 10-14 in humanized mice did not cause adverse effects on placenta and fetal development. (Funded by the Perinatal Health Center of Excellence: E0300201.).

The placenta: basics and clinical significance: edited by Berthold Huppertz and Ekkehard Schleubner, Berlin, Heidelberg, Springer, 2023, 371 pp., $159.99 (hardcover), $119 (e-book), ISBN: 978-3-662-66255-7, ISBN: 978-3-662-66256-4 (e-book)

The placenta is a vital yet poorly understood organ and given the increased interest in recent years in its role in human development and the birth process, histologic examinations are increasingly being performed and cause some consternation to both pathologists and histology laboratories. Different aspects of the placenta are covered including chapters on the normal histology and physiology, immunology, endocrinology, and imaging characteristics of the placenta. [Extracted from the article] Copyright of Journal of Histotechnology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

CD4+ T cells from preeclamptic patients cause hypertension, autoantibodies and cognitive dysfunction in a pregnant rat model

CD4+ T Cells from Preeclamptic patients with or without a history of COVID-19 during pregnancy cause hypertension, autoantibodies and cognitive dysfunction in a pregnant rat model Objective: Preeclampsia (PE) new onset hypertension (HTN) during pregnancy, is associated with increased autoantibodies, cerebral blood flow (CBF) impaired cognitive function and memory loss. We have shown adoptive transfer of placentalCD4+T cells from PE women into athymic nude pregnant rats causesHTNand autoantibodies associated with PE.COVID-19 (CV) during pregnancy is associated with increased diagnosis of PE. However, we do not know the role of CD4+ T cells stimulated in response to CV in contributing to the PE phenotype seen patients with a Hx of CV during pregnancy. Therefore, we hypothesize that adoptive transfer of placental CD4+ T cells from patients with a CV History (Hx) during pregnancy with PE causes HTN, increased CBF and cognitive dysfunction in pregnant athymic nude recipient rats. Study Design: Placental CD4+ T cells isolated from normotensive (NP), PE, Hx of CV normotensive (CV Hx NT), and Hx of CV with PE (CV Hx+PE) at delivery. One million CD4+ T cells were injected i.p. into nude athymic rats on gestational day (GD) 12. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function on GDs 15-19. Blood pressure (MAP) and CBF were measured by carotid catheter and laser Doppler flowmetry on GD19, respectively. A two-way ANOVA was used for statistical analysis. Result(s):MAPincreased inCVHx+PE (111 +/- 4, n = 4) and PE recipient rats (115 +/- 2 mmHg, n = 5) compared to CV Hx NT (100 +/- 4, n = 5) and NP (99 +/- 3 mmHg, n = 4, P < .05). CV Hx+PE and PE exhibited latency with errors navigating in the Barnes maze compared to CV Hx NT and NP groups. Locomotor activity was decreased in CV Hx+PE (P < .05) compared to PE, CV Hx NT, and NP groups. CV Hx+PE and PE spent more time exploring identical objects compared to CV Hx NT and NP groups. PE and CV Hx+ PE had increased CBF compared to CV Hx NT and NP rats. Conclusion(s): Our findings indicate that pregnant recipients of CD4+ T cells from PE with or without a Hx CV during pregnancy cause HTN, increased CBF and cognitive dysfunction compared to recipients of NP or NT Hx COVID-19 CD4+ T cells.

SARS-CoV-2 infection disrupts trophoblast function and placental syncytial barrier integrity via its accessory protein, ORF3a

Problem: Although it is rare for a SARS-CoV-2 infection to transmit vertically to the fetus during pregnancy, there is a significantly increased risk of adverse pregnancy outcomes due to maternalCOVID- 19. However, there is a poor understanding of such risks because mechanistic studies on how SARS-CoV-2 infection disrupts placental homeostasis are significantly lacking. The SARS-CoV-2 proteome includes multiple structural and non-structural proteins, including the non-structural accessory proteinORF3a. The roles of these proteins in mediating placental infection remain undefined. We and others have shown that autophagy activity in placental syncytium is essential for barrier function and integrity. Here, we have used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placenta exposed to SARS-CoV-2. The objective of our study was to investigate potential mechanisms through which SARS-CoV-2 impairs placental homeostasis and causes adverse pregnancy outcomes. We tested the central hypothesis that an essential SARS-CoV-2 non-structural and accessory protein, ORF3a, uniquely (amongst multiple viral proteins tested) with a novel three-dimensional structure andwith no homology to any other proteins is a key modulator of placental trophoblast cell dynamics via autophagy and intracellular trafficking of a tight junction protein (TJP), ZO-1. Method(s): We used clinical samples and cultured trophoblast cells to evaluate syncytial integrity of placentas exposed to SARS-CoV- 2. Autophagic flux was measured in placental villous biopsies from SARS-CoV-2-exposed and unexposed pregnant women by quantifying the expression of autophagy markers, LC3 and P62. Trophoblast cells (JEG-3, Forskolin-treated JEG-3, HTR8/SVneo, or primary human trophoblasts (PHTs)) were transfected with expression plasmids encoding SARS-CoV-2 proteins including ORF3a. Using western blotting, multi-label immunofluorescence, and confocal imaging, we analyzed the effect of ORF3a on the autophagy, differentiation, invasion, and intracellular trafficking of ZO-1 in trophoblasts. Using coimmunoprecipitation assays, we tested ORF3a interactions with host proteins. t-tests and one-way analyses of variance (ANOVAs) with post hoc tests were used to assess the data, with significance set at P < .05. Result(s): We discovered :1) increased activation of autophagy, but incomplete processing of autophagosome-lysosomal degradation;2) accumulation of protein aggregates in placentas exposed to SARS-CoV- 2. Mechanistically, we showed that the SARS-CoV-2 ORF3a protein, uniquely 3) blocks the autophagy-lysosomal degradation process;4) inhibits maturation of cytotrophoblasts into syncytiotrophoblasts (STBs);5) reduces production ofHCG-beta, a key pregnancy hormone that is also essential for STB maturation;and 6) inhibits trophoblast invasive capacity. Furthermore, ORF3a harbors an intrinsically disordered C-terminus withPDZ-bindingmotifs.We show for the first time that, 7) ORF3a binds to and co-localizes with the PDZ domain of ZO-1, a junctional protein that is essential for STB maturation and the integrity of the placental barrier. Conclusion(s): Our work outlines a new molecular and cellular mechanism involving the SARS-CoV-2 accessory protein ORF3a that may drive the virus's ability to infect the placenta and damage placental syncytial integrity. This implies that the mechanisms facilitating viral maturation, such as the interaction of ORF3a with host factors, can be investigated for additional functionality and even targeted for developing new intervention strategies for treatment or prevention of SARS-CoV-2 infection at the maternal-fetal interface.

Perinatal SARS-CoV-2 infection and vaccination: new insight

Cumulative data regardingCOVID-19 infection during pregnancy have demonstrated the ability of SARS-CoV-2 to infect the placenta. However, the mechanisms of SARS-CoV-2 placental viral entry are yet to be defined. SARS-CoV-2 infects cells by binding to the ACE2 receptor. However, SARS-CoV-2 cell entry also requires co-localization of spike protein cleavage by the serine protease TMPRSS2. However, the co-expression of ACE2 and TMPRSS2 in placental cells is debated, raising the question of whether potential non-canonical molecular mechanismsmay be involved in SARS-CoV-2 placental cells' viral entry. Although published data regarding the ability of the SARS-CoV- 2 to infect the fetus are contradicting, the placenta appears to be an immunological barrier to active SARS-CoV-2 infection and vertical transmission;however, the mechanism is unclear. Our experiments demonstrated the ability of the SARS-CoV-2 virus to directly infect the placenta and induce transcriptomic responses in COVID-positive mothers. These transcriptomic responses were characterized by differential expression of specific mRNAs and miRNAs associated with SARS-CoV-2 infection, with induction of specific placental miRNAs that can inhibit viral replication. Failure in such mechanisms may be associated with vertical transmission. Since the start of the COVID-19 pandemic, the COVID-19 mRNA vaccines have been widely used to reduce the morbidity and mortality of SARS-CoV-2 infection. Historically, non-live vaccines have not caused any harm to pregnant mothers;however, it is unclear whether our current understanding of the effects of non-live vaccines serves as a reliable precedent owing to the novel technology used to create these mRNA vaccines. Since there are no definitive data on the possible biodistribution of mRNA vaccines to the placenta, the likelihood of vaccine mRNA reaching the fetus remains uncertain. Little has been reported on the tissue localization of the lipid nanoparticles (LNPs) after intramuscular (IM) administration of the mRNA vaccine. The biodistribution of LNPs containing the mRNA vaccine has been investigated in animal models but not humans. In the murine model, the vaccine LNPs were rapidly disseminated to several organs, including the heart, liver, kidney, lung, and spleen, following IM administration. However, no traditional pharmacokinetic or biodistribution studies have been performed with the mRNA vaccines, including possible biodistribution to breast milk or the placenta.

COVID-19 in Pregnancy: Maternal, Placental and Fetal Implications

SARS-CoV-2 infection in pregnancy is associated with increased risk for severe COVID-19 disease including ICU admission, need for invasive ventilation, extracorporeal membrane oxygenation, and death. In addition, COVID-19 in pregnancy is associated with adverse pregnancy and neonatal outcomes. This presentation will review: (1) what is known about increased maternal and obstetric risk in the setting of SARS-CoV-2 infection;(2) how underlying comorbidities and viral strain may impact disease severity;(3) impact of COVID-19 in pregnancy on the placenta and how this may be altered by fetal sex and viral strain;(4) fetal risk and protection including vertical transmission, antibody-mediated protection, and later-life neurodevelopmental or metabolic risk in the setting of maternal immune activation.

Pandemic stress induces systemic immune changes and placental inflammation independently of SARS-CoV-2 infection in pregnancies

Problem: Environmental stress during pregnancy has known impacts on both maternal and fetal health. In terms of theCOVID-19 pandemic, the majority of published work has focused on the impact of the infection itself, without considering the potential immune impact of pandemic related-stress.We, therefore, assessed the impact of pandemic stress, independently of SARS-CoV-2 infection, on the circulating and placental immune profiles of pregnant individuals. Method(s): Placentas from 239 patients were collected at the Sainte- Justine Hospital, Montreal, Canada. Of these, 199 patients delivered during the pandemic and were exposed to pandemic stress with (+: 79) or without (-: 120) SARS-CoV-2 infection, the latter exposed to pandemic stress only. Pre-pandemic historic controls (uncomplicated pregnancies, Ctrl: 40), were also included. Placental biopsies were collected to assess cytokine levels by ELISAs and histopathological lesions. A sub-study with 35 pre-pandemic pregnancies (unexposed) and 20 who delivered during the pandemic (exposed) was also conducted. The latter (exposed/unexposed) were all uncomplicated pregnancies. We collected maternal blood prior to delivery for immunophenotyping, and plasma/peripheral blood mononuclear cells (PBMCs) were isolated. Inflammatory mediators in the plasma were quantified by ELISAs. Co-culture assays with PBMCs and human umbilical vein endothelial cells (HUVECs) were performed to assess endothelial activation. Demographical/obstetrical data were obtained through chart review. Result(s): SARS-CoV-2+ patients were multiethnic (63.4%), had higher pre-pregnancyBMI (28.9 vs. 24.8 inCtrl, P<.05), and elevated preterm birth rate (16.5% vs. 5.8% in SARS-CoV-2-, P < .05 and 0.0% in Ctrl, P < .01). In the placentas, we observed an increase in the levels of IL- 1Ra (P < .05) and CRP (P < .05) in both SARS-CoV-2 groups, while IL-6 (P = .0790) and MCP-1 (P < .001) were elevated solely in SARS-CoV- 2-. These changes were predominant in placentas with inflammatory lesions on histopathological analysis. Moreover, we observed elevated CD45+ cells (P < .001) in the placentas from both SARS-CoV-2 groups versus Ctrl. Considering that the differences we observed were important in the SARS-CoV-2- group, we performed a study solely on uncomplicated pregnancies, either exposed or unexposed to pandemic stress. At the systemic level, we observed a decrease in the percentage of Th2 cells (P < .001), leading to a pro-inflammatory Th1/Th2 imbalance in exposed individuals. Decreased Treg (P < .05) and Th17 (P < .05) versus unexposed was also observed. Surprisingly, decreased levels of circulating IL-6 (P < .05), MCP-1 (P < .01), and CRP (P<.05) were seen in exposed versus unexposed individuals. Finally,we observed increased secretion of ICAM, a marker of endothelial activation, solely in endothelial cells co-cultured with PBMCs from exposed individuals. Conclusion(s): Overall, placental inflammatory profiles differed between pregnant individuals exposed to pandemic stress with or without SARS-CoV-2 infection. Moreover, we observed that the pandemic stress exposed group presented a systemic pro-inflammatory bias. This highlights the need to understand the differences between the effects of pandemic-related stress and the added burden of SARS-CoV-2 infection itself on maternal and fetal health. Our work also supports an association between an increased risk of hypertension/ preeclampsia and SARS-CoV-2 infection that might be driven in part by pandemic-related stress.

Macerated stillbirth

Stillbirth is defined as the birth of a viable baby without signs of life. They account for more than 2.5 million intrauterine deaths per year worldwide and are associated with a number of risk factors, the most important of which are maternal and placental factors. Autopsy provides information that may be of use in determining time since death, gestational age of the fetus, mode of death, cause of fetal demise, and the likelihood of recurrence. The format of the autopsy is guided by parental consent, but even when consent is limited, valuable information may be obtained by careful consideration of antemortem test results, imaging, and genetic testing. Where there is a delay between death and delivery, fetuses are affected by maceration, which may increase the technical complexity of the autopsy and impart a number of artefactual changes, which should not be misinterpreted as genuine pathology. The most common pathologies encountered at autopsy are placental abnormalities, changes related to maternal disorders, malformations, and central nervous system pathology. © Springer Nature Switzerland AG 2022. All rights reserved.

Does COVID-19 infection acquired in different pregnancy trimester influence placental pathology?

OBJECTIVES: To determine the morphological characteristics of the placentas from COVID-19 positive mothers in regard to the trimester of COVID-19 infection onset and low weight molecular heparin (LMWH) treatment. METHODS: Placentas were collected in the period April 1st till September 1st 2021 after delivery at Department of Obstetrics and Gynecology University Hospital Split, Croatia, and sent for pathological examination. Medical history and pathology reports were used to collect the data. Pregnant women were divided based on the onset of COVID-19 infection and stratified into low molecular weight heparin (LMWH)+ or LMWH-. Depending on the data distribution, the following test were used: chi-squared test. Student's t-test, Mann-Whitney U test, ANOVA and Kruskal-Wallis test. RESULTS: In 38% of patients the onset of COVID-19 infection was the 1st trimester of pregnancy, in 27% in the 2nd and 35% of women were infected in the 3rd trimester The fetal vascular malperfusion (FVM) occurrence was statistically significantly higher in the LMWH- group and if the onset of infection was in the 2nd trimester, while the perivillous fibrin deposition was most likely to happen if the COVID-19 infection that occured in the 1st trimester of pregnancy. CONCLUSIONS: The onset of COVID-19 infection has the influence on trophoblast damage and subsequent morphological appearance of the placenta. LMWH use in COVID positive pregnant women decreases the rate of the FVM in examined placentas.

Potential influence of COVID-19 and dexamethasone on the reproductive system: what we know and can expect.

Dexamethasone is the first and an important therapy that significantly reduces the risk of death in patients with severe COVID-19 disease. Nevertheless, a lot of studies have revealed that it has adverse impacts on multiple systems of the body especially the reproductive system, and dexamethasone exposure during the human foetal period may be associated with various diseases. In this paper, we reviewed the literature regarding the adverse effects of COVID-19 and dexamethasone administration on the reproductive system as well as related disease pathogenesis, in an attempt to clarify the potential harms of dexamethasone treatment in COVID-19 patients. Overall, we strongly support the application of dexamethasone as a pharmaceutical therapy in critical COVID-19 patients before a better therapy is developed, but the adverse side effects that may arise cannot be ignored. Our review will help medical professionals in the prognosis and follow-up of patients treated with dexamethasone. In addition, given that a considerable amount of uncertainty, confusion and even controversy that still remains, further studies and more clinical trials are urgently needed to improve the understanding of the parameters and the effects of dexamethasone on reproductive function of patients with severe acute respiratory syndrome coronavirus 2 infection.

Vaccination is preventing development of placental pathologies in SARS-CoV-2 infected pregnant patients.

INTRODUCTION: The coronavirus disease (COVID-19) has created a serious health problem in pregnant people. We aimed to address whether vaccination can prevent development of placental disease in SARS-CoV-2 infected mothers. METHODS: We reported the pathology findings obtained from routine histopathological examination of placentas of overall 38 cases. RESULTS: We found low prevalence of placental pathology in vaccinated pregnant people with active SARS-CoV-2 infection in comparison to those unvaccinated cases. CONCLUSION: Based on our findings, SARS-CoV-2 vaccination can prevent development of placental pathological lesions and may lower the risk of serious illness in pregnant people.

COVID-19 and Placental Infection: Are Fetal Survivors at Risk of Long-Term Cardiovascular Complications?

As we enter the fourth year of the coronavirus disease 2019 (COVID-19) pandemic, it has become obvious that adult survivors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are susceptible to numerous complications in various organ systems. SARS-CoV-2 placental infection is an unanticipated complication of COVID-19 during pregnancy. We hypothesize that fetal survivors of SARS-CoV-2 placentitis are susceptible to long-term cardiovascular complications.

Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission.

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.

On the structural reorganization in the placentas of women who underwent COVID-19 in the first and second trimesters of pregnancy

Objective. To study the peculiarities of structural and functional reorganization in the placentas of COVID-19 patients in the I and II trimesters of pregnancy. Material and methods. Twenty-six patients who had undergone COVID-19 in the first or second trimesters of pregnancy in different forms (the study group) and 20 patients with term physiological pregnancy (the control group) were examined. A morphological study of the placenta was carried out and the results were compared between the study and control groups. To assess structural reorganization in the placentas of both groups, we calculated the relative volume density of villi of different types per conventional unit area and the relative area of syncytial nodules. Results. Areas with a predominance of intermediate differentiated and undifferentiated villi were found in the placentas of the COVID-19-treated pregnant women in the first trimester and asymptomatic form, which indicated a tendency to delay their maturation. Compared with the results in the control group, the relative area of syncytial nodules was increased in the placentas of women who underwent COVID-19 in the first trimester of pregnancy. The placentas of women who underwent COVID-19 in the second trimester showed the greatest structural abnormalities — the bulk density of the terminal villi decreased, which was possibly associated with the formation of intermediate undifferentiated and differentiated villi between weeks 13 and 28. Conclusion. Study of structural reorganization in the placentas of women who underwent COVID-19 in the first and second trimesters of pregnancy reveals new links in the pathogenesis of the disease depending on its severity and helps to correctly assess the condition of the mother and her newborn. © 2023, Media Sphera Publishing Group. All rights reserved.