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.

Protein S Deficiency with Favourable Foetomaternal Outcome: A Case Report

Protein S is a multifunctional plasma protein, whose deficiency, results in a rare congenital thrombophilia, inherited in an autosomal dominant pattern. It can aggravate the hypercoagulable state of pregnancy, when it presents in parallel with the condition, leading to adverse maternal outcomes and foetal loss. A 35-year-old female third gravida having previous 2 deliveries by Lower Segment Caesarean Section (LSCS) presented to emergency at 10 weeks pregnancy with chief complaints of pain and swelling in left thigh since 4-5 days. After thorough investigations and work-up, the patient was diagnosed with Protein S deficiency. She was managed conservatively and was delivered by elective LSCS with bilateral tubal ligation at 38 weeks of gestation with good foetal and maternal outcomes.The rarity of Protein S deficiency along with the successful outcome of the pregnancy makes this a unique case.Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

ACE2 expression in the brain during development and susceptibility to brain infection by SARS-COV-2.

The COVID-19 pandemic spread around the world due to the enormous transmission of the SARS-CoV-2 among humans. COVID-19 represents a threat to global public health. The entry of this virus into cells is greatly facilitated by the presence of angiotensin-converting enzyme 2 (ACE2) in the cell membrane. Today we do not have a precise understanding of how this receptor expresses in the brain during human development and, as a consequence, we do not know whether neural cells in the developing brain are susceptible to infection. We review the knowledge about ACE2 expression in the developing human brain, with special attention to the fetal stage. This stage corresponds to the period of the cerebral cortex formation. Therefore, SARS-CoV-2 infection during the fetal period may alter the normal development of the cerebral cortex. Although few cases have been published demonstrating vertical transmission of SARS-CoV-2 infection, the large number of infected young people may represent a problem which requires health surveillance, due to the possibility of cognitive alterations and abnormalities in the development of cortical circuits that may represent a predisposition to mental problems later in life.Copyright © 2023, Instituto de Investigaciones Medicas. All rights reserved.

Impact of COVID-19 on Pregnancy and Maternal-Neonatal Outcomes: A Narrative Review.

The pandemic coronavirus disease (COVID-19) has caused an unprecedented worldwide health emergency. The pandemic increased the susceptibility of pregnant women to maternal and fetal complications. Elderly and patients with comorbidities were also at high risk during the pandemic times. Further evidence supports that COVID-19 is not only a respiratory infection but possibly affects other organ systems, including the placenta. The key objective of this review is to explore the literature on COVID-19-affected pregnancies and study the pandemic's impacts on maternal, perinatal, and neonatal outcomes. We used Google Scholar and PubMed (Medline) for relevant literature searches. The clinical manifestations in pregnant women, fetus outcome, vertical transmission, and early and late pregnancy impacts are combined in database studies. Women should receive special attention for COVID even though most of the COVID-19-positive pregnant women had no symptoms or had minor ones. It was found that most pregnant women with COVID-19 had mild and few symptoms and that the effect on the fetus was insignificant. However, in some women, miscarriage and fetal growth retardation were seen as a consequence of the infection.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.

Placentas from Mothers with Positive SARS-CoV-2 (COVID-19) Test Results at Labor Showed Neither Specific Histopathological Changes Nor Evidence of COVID-19 Infection

Background: Evidence has shown that pregnancy is a risk factor for severe illness in women with SARS-CoV-2 (COVID-19). Yet their newborns are mostly doing well. The placenta is a complex, highly specialized, but poorly understood organ. The COVID-19 infection related specific pathological changes in placenta and prevalence of transplacental transmission of COVID-19 has not been fully explored and validated. Design: Universal screening for COVID-19 among all pregnant women on admission to labor and delivery unit was initiated in April 2020 at our institute. With IRB approval, 54 term pregnant women with positive COVID-19 nasopharyngeal swap results at admission during April 2020 to Jun 2021 were recruited. Patients' demographic characteristics and clinical presentation were summarized in Table 1. Histopathology of all placentas was independently reviewed by two board certified pathologists. RNA was extracted from Formalin-Fixed Paraffin-Embedded (FFPE) blocks of 15 randomly selected placentas. ThermoFisher TaqPathTM SARS-CoV-2/COVID-19 RT-PCR assays were performed to detect the presence of the virus with proper controls. Results: Hispanic or Latino pregnant women represented 39% of the study cohort tested positive for COVID-19 at admission, followed by American Africa (26%) and Caucasian (17%). Most patient were overweight before pregnancy and 1/3 patients had at least one comorbidity. Majority patients (72%) were completely asymptomatic. The rest of patients had somewhat mild symptoms including sore throat, cough, low-grade fever, and/or loss of taste/smell. All deliveries were term. All neonates were in healthy status at birth. No suspected vertical transmission was observed. Histopathological inspection of placentas showed nonspecific features of maternal or fetal vascular malfunction and inflammation (Table 2). Among 15 placental samples tested, no SARS-CoV-2 virus was detected. Conclusions: Multiple studies indicated that only a very small proportion of neonates delivered to mothers with COVID-19 infection were also tested positive for COVID-19. Our data suggested that COVID-19 infected mothers who were asymptomatic or only with mild symptoms at labor unlikely vertically transmit the virus through the placenta. This finding may ease the anxiety of asymptomatic mothers caused by positive COVID-19 test result at delivery admission. (Table Presented).

Maternal-Fetal Implications of SARS CoV-2 Infection during Pregnancy, Viral, Serological Analyses of Placenta and Cord Blood.

OBJECTIVE: There are few data on the maternal-fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns' samples and search antibodies in cord blood. METHODS: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers' blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications. RESULTS: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers' samples. IgM was negative in the 23 cord blood samples. CONCLUSIONS: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood samples of newborns. They are possibly of maternal origin, suggesting a probable mechanism of fetal protection against SARS-CoV-2 infection. No SARS-CoV-2 IgM was found in the cord blood samples. Detection of SARS-CoV-2 in placenta is rare.

Integrated Analysis Reveals the Characteristics and Effects of SARS-CoV-2 Maternal-Fetal Transmission.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a pandemic of coronavirus disease 2019 (COVID-19) and is threatening global health. SARS-CoV-2 spreads by air with a transmission rate of up to 15%, but the probability of its maternal-fetal transmission through the placenta is reported to be low at around 3.28%. However, it is still unclear that which tissues and developmental periods hold higher risks and what the underlying molecular mechanisms are. We conducted an integrated analysis of large-scale transcriptome and single-cell sequencing data to investigate the key factors that affect SARS-CoV-2 maternal-fetal transmission as well as the characteristics and effects of them. Our results showed that the abundance of cytomegalovirus (CMV) and Zika virus (ZIKV) infection-associated factors in the placenta were higher than their primarily infected tissues, while the expression levels of SARS-CoV-2 binding receptor angiotensin-converting enzyme II (ACE2) were similar between lung and placenta. By contrast, an important SARS-CoV-2 infection-associated factor, type II transmembrane serine protease (TMPRSS2), was poorly expressed in placenta. Further scRNA-Seq analysis revealed that ACE2 and TMPRSS2 were co-expressed in very few trophoblastic cells. Interestingly, during the embryonic development stages, the abundance of ACE2 and TMPRSS2 was much higher in multiple embryonic tissues than in the placenta. Based on our present analysis, the intestine in 20th week of embryonic development was at a high risk of SARS-CoV-2 infection. Additionally, we found that during the fetal development, ACE2 and TMPRSS2 were enriched in pathogen infection-associated pathways and may involve in the biological processes related to T-cell activation. In conclusion, our present study suggests that though the placenta provides a good physical barrier against SARS-CoV-2 infection for healthy fetal development, multiple embryonic tissues are under risks of the virus infection, which may be adversely affected once infected prenatally. Therefore, it is necessary to enhance maternal care to prevent the potential impact and harm of SARS-CoV-2 maternal-fetal transmission.

Innate Immune Response to Viral Infections at the Maternal-Fetal Interface in Human Pregnancy.

The placenta, the first and largest organ to develop after conception, not only nurtures and promotes the development of the conceptus, but, it also functions as a barrier against invading pathogens. Early phases of pregnancy are associated with expansion of specific subsets of Natural Killer cells (dNK) and macrophages (dMφ) at the maternal uterine mucosa, the basal decidua. In concert with cells of fetal origin, dNK cells, and dMφ orchestrate all steps of placenta and fetus development, and provide the first line of defense to limit vertical transmission. However, some pathogens that infect the mother can overcome this protective barrier and jeopardize the fetus health. In this review, we will discuss how members of the classical TORCH family (Toxoplasma, Other, Rubella, Cytomegalovirus, and Herpes simplex virus) and some emerging viruses (Hepatitis E virus, Zika virus, and SARS-CoV2) can afford access to the placental fortress. We will also discuss how changes in the intrauterine environment as a consequence of maternal immune cell activation contribute to placental diseases and devastating pregnancy outcomes.

Neonates with coronavirus disease 2019 acquired from infected mothers: the incompatibility of maternal intensity and infant lung involvement: two case reports.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a public health emergency by the World Health Organization on January 30, 2020. The results of recent studies have suggested that neonates may present symptoms of COVID-19. Although the presentation of the disease in neonates is known to vary, only a limited number of studies have investigated newborns infected with COVID-19. CASE PRESENTATION: This study presents two Asian cases of newborns with COVID-19. Maternal-fetal or postnatal transmission was suggested based on the simultaneity of maternal infection. Chest radiography in one of the neonates showed severe lung involvement. Despite support and resuscitation attempts, the poor clinical condition of the neonate led to his death. However, the two mothers and one of the neonates were discharged from the hospital in good general condition. CONCLUSION: The neonates had worse clinical conditions than the mothers, and the intensity of pneumonia and level of lung involvement in the newborns were not associated with the stage and severity of the disease in the mothers with COVID-19.

Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19.

A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.

Investigating the risk of maternal-fetal transmission of SARS-CoV-2 in early pregnancy.

INTRODUCTION: The possibility of vertical transmission of SARS-CoV-2 from the mother to the fetus is one of the most crucial issues regarding the COVID-19 effects on pregnancy. In this study, we aimed to explore the risk of maternal-fetal transmission before 24 weeks of gestation, through analysis of abortion materials collected from PCR-positive women with pregnancy loss. To the best of our knowledge, apart from case reports, this study is the first prospective work on the vertical transmission of SARS-CoV-2 in early pregnancy. METHODS: The patients who had attended our clinic with the diagnosis of pregnancy loss before 24 weeks of gestation were screened for COVID-19. Vertical transmission in PCR-positive women was assessed through the presence of SARS-CoV-2 RNA in fetal-placental tissues by rt-PCR test. RESULTS: 24 of 210 (%11,4) pregnant women participating in the study had positive rt-PCR results. Placenta and curettage material samples of these PCR-positive patients were analyzed and all valid test results (21 samples) were negative for SARS CoV-2 RNA. In three cases, the rt-PCR results were invalid due to failed internal controls. DISCUSSION: In the literature, the possibility of intrauterine vertical transmission of SARS-CoV-2 is still controversial. The findings of the present study did not reveal any evidence of vertical transmission of SARS-CoV-2 in early pregnancy.

SARS-CoV-2 and the reproductive system: known and the unknown..!!

BACKGROUND: COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time. MAIN BODY OF ABSTRACT: Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases. CONCLUSION: Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.

Pregnancy and Childbirth in the COVID-19 Era-The Course of Disease and Maternal-Fetal Transmission.

From the beginning of the Coronavirus Disease 2019 (COVID-19) pandemic, special attention has been paid to pregnant women and to monitoring comorbidities, such as gestational diabetes and hypertension, which could increase their risk of disease and death. The purpose of this review is to synthesize the available knowledge on the course of COVID-19 in pregnant women as well as the risk of maternal-fetal transmission. The study indicated that the course of COVID-19 is worse in pregnant women who are more often admitted to intensive care units or who require mechanical ventilation than nonpregnant women with COVID-19. Some symptoms, such as dyspnea and cough, were similar to those observed in nonpregnant women, but fever, headache, muscle aches, chills, and diarrhea were less frequent. A study revealed that premature delivery and cesarean section were more common in pregnant women diagnosed with COVID-19. In addition, recent studies confirm the possibility of intrauterine maternal-fetal transmission by positive genetic tests and the presence of IgM in newborns just after delivery; at the moment, the probability of transmission through mother's milk is inconclusive. Considering all the above, a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is an important factor that threatens the health and life of both the mother and the fetus, but further studies are still needed.

[Infection with SARS-CoV-2 in pregnancy. Update of Information and proposed care. CNGOF]. / Infection par le SARS-CoV-2 chez les femmes enceintes. Actualisation de l'état des connaissances et de la proposition de prise en charge. CNGOF.

OBJECTIVES: The coronavirus SARS-CoV-2 identified late 2019 in China had spread across all continents. In the majority of cases, patients have mild symptoms (fever, cough, myalgia, headache, some digestive disorders) or are asymptomatic, however it can cause serious lung diseases and lead to death. On September 2020, over 28 million people have been infected with over 920,000 deaths. METHODS: In view of the evolution of the epidemic the French National College of Obstetricians and Gynecologists has decided to update the recommendations previously issued. To do this, the same group of experts was called upon to carry out a review of the literature and take into account the opinions of the General Directorate of Health (DGS), the "Haute Autorité de Santé" (HAS) and the "Haut Conseil de santé Publique" (HCSP). RESULTS: The data on consequences during pregnancy have accumulated. The symptoms in pregnant women appear to be similar to those of the general population, but an increased risk of respiratory distress exists in pregnant women especially in the third trimester. A case of intrauterine maternal-fetal transmission has been clearly identified. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. CONCLUSION: In light of the new data, we propose updated recommendations. These proposals may continue to evolve in view of the pandemic and of advances in studies in pregnant women.

[SARS-CoV-2 infection during pregnancy. Information and proposal of management care. CNGOF]. / Infection par le SARS-CoV-2 chez les femmes enceintes : état des connaissances et proposition de prise en charge par CNGOF.

A new coronavirus (SARS-CoV-2) highlighted at the end of 2019 in China is spreading across all continents. Most often at the origin of a mild infectious syndrome, associating mild symptoms (fever, cough, myalgia, headache and possible digestive disorders) to different degrees, SARS-Covid-2 can cause serious pulmonary pathologies and sometimes death. Data on the consequences during pregnancy are limited. The first Chinese data published seem to show that the symptoms in pregnant women are the same as those of the general population. There are no cases of intrauterine maternal-fetal transmission, but cases of newborns infected early suggest that there could be vertical perpartum or neonatal transmission. Induced prematurity and cases of respiratory distress in newborns of infected mothers have been described. Pregnancy is known as a period at higher risk for the consequences of respiratory infections, as for influenza, so it seems important to screen for Covid-19 in the presence of symptoms and to monitor closely pregnant women. In this context of the SARS-Covid-2 epidemic, the societies of gynecology-obstetrics, infectious diseases and neonatalogy have proposed a French protocol for the management of possible and proven cases of SARS-Covid-2 in pregnant women. These proposals may evolve on a daily basis with the advancement of the epidemic and knowledge in pregnant women. Subsequently, an in-depth analysis of cases in pregnant women will be necessary in order to improve knowledge on the subject.