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 Effect of COVID-19 on the Human Reproductive System: A Review Study

Background: Evidence reveals that COVID-19, in addition to impacting the respiratory system, affects other organs, including the male and female reproductive systems. The purpose of this study was to examine the impact of COVID-19 on the human reproductive system. Method(s): Data were collected in SID, Science Direct, PubMed, and Google Scholar databases. The Keywords including COVID- 19, reproductive system, fertility, and factors related to mesh term utilization and Boolean strategy were used. Papers from 2019 to 2022 were extracted. Finally, out of 58 searched articles, 20 articles related to the purpose of the study were reviewed. Result(s): The results were organized into two categories. The first category deals with the effect of COVID-19 on the female reproductive system including Sleep disorders following quarantine on gonadotropin release and its effect on the ovaries and menstrual cycle, preterm delivery, increased cesarean delivery, the possibility of intrauterine infection of the fetus and dysfunction of the reproductive glands. The second category concerns the effect of COVID-19 on the male reproductive system including abnormal semen quality, possible effect on gonocyte differentiation in the early stages of spermatogenesis, negative effect on spermatogenesis, testicular dysfunction, and changes in testosterone concentration by increasing serum LH, testicular inflammation, decreased sperm concentration in semen, impaired sperm motility, dysfunction of the reproductive glands, significant damage to the seminiferous tube, swelling of Sertoli cells, decreased Leydig cells, significant disorder on semen volume and impaired sperm morphology. Conclusion(s): The findings revealed that COVID-19 has an impact on various aspects of the human reproductive system. Midwives and gynecologists should alleviate couples' fears about infertility by recognizing these cases and offering suitable counseling to couples infected with COVID-19.

Aplasia cutis congenita in dizygotic twin infants

Aplasia cutis congenita (ACC) is often sporadic, but familial cases have been reported. We report a case of a dichorionic diamniotic twin pregnancy in which both the male and female twins had matching areas of aplasia cutis on their scalps. An Irish couple sought fertility treatment using a donor egg and paternal sperm. Successful in vitro fertilization (IVF) and the transfer of two embryos resulted in a diamniotic dichorionic twin pregnancy. Two fetal poles were noted at the 12-week ultrasound (US) scans. The mother suffered from a minor urinary tract infection during the first trimester but had no other history of infection, including herpes simplex virus or COVID- 19. She was known to be varicella immune prior to pregnancy. The twins were born by elective caesarean section owing to breech presentation. Twin one was female and twin two was male. Both infants were born with scarring on the crown of their head, which was consistent with ACC. Cranial US showed no underlying bony abnormality. The rest of the cutaneous examination was normal and there were no other congenital anomalies. ACC is a rare, heterogeneous group of disorders characterized by the congenital absence of skin, which can be focal or widespread. It is thought to affect 1-3 per 10 000 live births. The exact cause of ACC is unclear. Various hypotheses have been suggested, including defective closure of the neural tube or embryonic fusion lines, intrauterine trauma, placental insufficiency, fetus papyraceus, amniotic membrane adhesions, intrauterine infections, teratogens and genetic mutations. The classification of ACC is based on the area affected, type of skin irregularity, associated congenital defects and mode of inheritance. Scalp ACC without multiple anomalies (category 1) is generally associated with an autosomal dominant or sporadic pattern of inheritance. These twins may have an autosomal dominant mutation that led to this phenotype. ACC can also be associated with fetus papyraceus or placental infarct. This is less likely in this case as only two embryos were transferred, and the pregnancy was dichorionic. Most cases of ACC associated with fetus papyraceus occur in monozygotic pregnancies. ACC lesions often heal spontaneously by re-epithelialization resulting in a hairless superficial scar. Twin one had a slightly smaller area affected by ACC and overlying eschar resolved several weeks after birth. Twin two has had no hair growth in the area. This case highlights the difficulties in ascertaining the aetiology of this rare condition in twin pregnancies.

Haemostatic parameters in pregnant women with a new coronavirus infection COVID-19

Objective. To improve perinatal outcomes in pregnant women with a new coronavirus infection COVID-19 by optimizing diagnostic, therapeutic, and prophylactic measures. Material and methods. The course of pregnancy, labor and perinatal outcomes were studied in 70 patients with COVID-19 during the present pregnancy who were delivered at the Moscow Regional Research Institute of Obstetrics and Gynecology (MORRIOG). The patients were divided into 2 groups depending on the timing of their visit to the outpatient department of MORRIOG: Group 1 comprised 45 pregnant women with new-onset coronavirus infection in the first to second trimesters of gestation, with subsequent presentation and follow-up at the MORRIOG outpatient department;Group 2 comprised 25 pregnant women who had new-on-set coronavirus (NCD) infection during gestation and presented to the outpatient department before delivery. In addition to a general clinical examination, all pregnant women underwent an extended haemostatic analysis, including a thrombodynamic test. Results. Analysis of the findings showed that hypercoagulable changes in the hemostatic system were observed in pregnant women with COVID-19 infection during gestation, but standard hemostatic tests did not reflect the characteristic postinfectional changes compared with the results of an extended coagulation potential study using the thrombodynamics test. Hypercoagulative changes were revealed irrespective of the severity of the COVID-19, which could be due to the combination of several risk factors and the presence of concomitant extragenital diseases. Conclusion. The most favorable gestational outcome in patients who have suffered a COVID-19 infection during pregnancy depends on the timely of the detection of hemostasis abnormalities after comprehensive examination and on the composition of available pathogenetic therapy. Rational anticoagulant and antiplatelet therapy under control of the coagulation parameters and achievement of normalization of coagulation tests result in a significant reduction in adverse obstetric and perinatal outcomes. © 2023, Media Sphera Publishing Group. All rights reserved.

Haemostatic parameters in pregnant women with a new coronavirus infection COVID-19

Objective. To improve perinatal outcomes in pregnant women with a new coronavirus infection COVID-19 by optimizing diagnostic, therapeutic, and prophylactic measures. Material and methods. The course of pregnancy, labor and perinatal outcomes were studied in 70 patients with COVID-19 during the present pregnancy who were delivered at the Moscow Regional Research Institute of Obstetrics and Gynecology (MORRIOG). The patients were divided into 2 groups depending on the timing of their visit to the outpatient department of MORRIOG: Group 1 comprised 45 pregnant women with new-onset coronavirus infection in the first to second trimesters of gestation, with subsequent presentation and follow-up at the MORRIOG outpatient department;Group 2 comprised 25 pregnant women who had new-on-set coronavirus (NCD) infection during gestation and presented to the outpatient department before delivery. In addition to a general clinical examination, all pregnant women underwent an extended haemostatic analysis, including a thrombodynamic test. Results. Analysis of the findings showed that hypercoagulable changes in the hemostatic system were observed in pregnant women with COVID-19 infection during gestation, but standard hemostatic tests did not reflect the characteristic postinfectional changes compared with the results of an extended coagulation potential study using the thrombodynamics test. Hypercoagulative changes were revealed irrespective of the severity of the COVID-19, which could be due to the combination of several risk factors and the presence of concomitant extragenital diseases. Conclusion. The most favorable gestational outcome in patients who have suffered a COVID-19 infection during pregnancy depends on the timely of the detection of hemostasis abnormalities after comprehensive examination and on the composition of available pathogenetic therapy. Rational anticoagulant and antiplatelet therapy under control of the coagulation parameters and achievement of normalization of coagulation tests result in a significant reduction in adverse obstetric and perinatal outcomes. © 2023, Media Sphera Publishing Group. All rights reserved.

Effects of COVID-19 on Pregnant Women and Newborns: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus originated in Wuhan, China, and spread all over the world, causing the worst pandemic of the century. The disease has a broad continuum of clinical presentations, from mild to life-threatening. The virus is highly contagious and transmittable to humans. Emerging evidence of its effects on pregnant women and newborns is inconsistent and ever-evolving. Therefore, the objective of this review is to compile the scientific literature on the effects of SARS-CoV-2 coronavirus on pregnancy, pregnant women, and newborns. Data were obtained by several authors using PubMed, MEDLINE, Google Scholar, and Web of Science. "COVID-19", "pregnancy", "vertical transmission", and "newborn" were the search words used to find relevant articles. Most studies suggested pregnant women and newborns are not at additional risk for unfavorable outcomes. Besides, very few studies found newborns who tested positive for SARS-CoV-2 upon delivery from a COVID-positive mother. However, several studies showed no evidence of intrauterine or transplacental transmission of COVID-19 infection. Studies had mixed findings with a few showing the presence of the virus in breastmilk. In conclusion, there is no concrete evidence of additional adverse effects of SARS-CoV-2 on pregnant women and newborns.

SARS-Cov2-Induced Cytokine Storm and Schizophrenia, Could There be a Connection?

Today, a new coronavirus (2019-nCoV, later named SARS-CoV-2) has become known as a pandemic with over 3,949,200 cases and 271,782 deaths. It has been considered that most of the deaths in infected patients stem from co-morbidity conditions. Therefore, understanding at-risk populations are currently under the focus of investigations. This object has highly driven attention to put patients with a higher potential of death related to SARS-CoV2 infection at priority. For instance, this can happen in Schizophrenia owing to ambiguous immunology attributes, including elevated levels of pro-inflammatory cytokines and stress-related immune disability. Given that, the hyper-inflammatory responses are the significant cause of the pathophysiology of the SARS-CoV2-related mortality. Moreover, SARS-CoV2 can prompt the risk of developing Schizophrenia in the future. This review punctuates that prenatal/perinatal infection could be associated with increased Schizophrenia risk;on the flip side, the potential risk of ongoing medication can worsen mentally disabled patients, and healthy people are at risk.

Umbilical cord vascular thrombosis: literature review and two clinical cases

Thrombosis of the umbilical cord vessels is a rare complication of pregnancy, combined with a high level of perinatal morbidity and mortality. Anomalies of vascular attachment (velamentous attachment), pathology of the umbilical cord (hyperspiralization, short or long umbilical cord), intrauterine infections, maternal diabetes mellitus and preeclampsia as well as meconium found in the amniotic fluid are among the risk factors of developing thrombosis in the umbilical cord vessels. Here we present two clinical observations of umbilical vein thrombosis at full-term pregnancy. In both cases, during pregnancy and childbirth, no signs of umbilical cord pathology were found according to cardiotocography and Doppler ultrasound;despite this, the children were born in hypoxic state. Both newborns were transferred to the second stage of treatment due to suspected intrauterine pneumonia. Velamentous attachment, intrauterine infections as well as meconium found in the amniotic fluid were the risk factors of developing umbilical vein thrombosis described in case 1 and case 2, respectively. During pregnancy, both female patients suffered from clinically confirmed novel coronavirus infection (COVID-19) and contacted patients with COVID-19 in the third trimester of gestation. It is likely that endothelial damage caused by the novel coronavirus SARS-CoV-2 was one of the risk factors for the development of umbilical vein thrombosis, but this issue requires to be further explored.

Features of the Course of Pregnancy and Childbirth in Women with COVID-19 Infection in the First and Second Trimesters of Pregnancy

Infection carried by pregnant women with COVID-19 in the first and second trimesters of pregnancy can have an adverse effect on the formation of obstetric complications associated with the pathology of implantation. We examined 109 pregnant women with laboratory-confirmed COVID-19 infection by PCR at 4 weeks gestation – 21 weeks 6 days. The most frequent symptoms of the disease in these pregnant women were fever in 82 (75.2%) and anosmia, which was often combined with ageusia in 73 (66.9%). Rare manifestations were myalgia in 12 (11%) pregnant women, shortness of breath in 7 (6.4%), rhinorrhea in 7 (6.4%), complaints of a feeling of heaviness in the chest in 4 (3.7%). We established a decrease in the free β-hCG index to 0.94 (0.64–1.30) MoM. The incidence of fetal urinary tract damage was 7 (6.4%), of which 4 (3.7%) had congenital malformations. All childbirth was urgent. The average delivery time was 38.6 (37–42) weeks. Labor in 8% was complicated by the developed distress syndrome of the fetus in labor, which required the completion of labor by emergency caesarean section. © 2022, Professionalnye Izdaniya. All rights reserved.

New COVID-19 and pregnancy

The problemof infectious diseases arising in pregnant women occupies the minds of not only specialists in the field of obstetrics and gynecology, but also physiologists, embryologists, and infectious disease specialists. Currently, one of the most actual topics is the infection caused by the new coronavirus SARS-CoV-2, which today is acquiring not only medical, but also, of course, social significance. On March 11, 2020, the World Health Organization declared the COVID-19 pandemia. However, the adaptive changes characteristic of pregnancy, such as an increase in circulating blood volume, an increase in oxygen demand, immunological changes, the tendency of pregnant women to dominate the T2-helper (Th2) system, which protects the fetus, and the mother is more vulnerable to viral infections, which are more effective being hold back by the Th1 system, can contribute to a high susceptibility to infections and an increase in the risk of complications. All this requires an integrated approach to pregnancies with SARS-CoV-2 infection. The high-risk group includes pregnant women with extragenital diseases (cardiovascular, respiratory system diseases (pneumonia, bronchial asthma), diabetes, autoimmune diseases, tumors), with a history of surgical interventions, with complicated obstetric history, pregnant women in the second and especially in the third trimesters. Moreover, it is necessary to take into account the experience of previous epidemics of coronavirus infections — SARS and MERS, during which in 2002-2003. there have been cases of maternal mortality, spontaneous abortions in the first trimester, intrauterine growth retardation, and premature birth. Vertical transmission of SARSCoV and MERS-CoV has not been confirmed, but pregnant women have had a more severe clinical course of infections compared to non-pregnant women. Taking into account these facts, it is necessary to carefully monitor the course of pregnancy, taking into account the risk of the formation of its complications. This review summarizes the available data highlighting these issues in foreign sources, including the clinical guidelines of the Royal Society of Obstetricians and Gynecologists (UK), the American Society of Obstetricians and Gynecologists (USA), the National Institute for Reproductive Health Research (India) of the management of pregnant women and delivery. infected with the SARS-CoV-2 coronavirus. © E.V. DULAEVA, E.B. EFIMKOVA, S.V. NOVIKOVA.

Clinical features of neonates born to mothers with coronavirus disease-2019: A systematic review of 105 neonates.

BACKGROUND: Despite the increasingly recognized impact of novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), on many aspects of health in adults and children, its effects on neonates born to infected mothers remain unclear. We conducted this study to investigate the outcomes of neonates born to mothers with COVID-19. METHODS: We searched the medical databases from inception to March 31, 2020 to perform a systematic review of outcomes in neonates born to mothers with COVID-19. Data were pooled using a random effects regression model. Primary and secondary outcomes were neonatal clinical outcomes and infectious status, respectively. RESULTS: Fourteen studies involving 105 neonates fulfilling the study criteria were identified. The rates of preterm neonates and those small for gestational age (SGA) were 25 (23.8%) and 10 (11.2%), respectively. Among 91 neonates who were tested, 8 (8.8%) were positive for nucleic acids or antibodies for SARS-CoV-2. Additionally, 28 (26.7%) of the neonates were symptomatic and two test-negative neonates died, including one stillbirth. Between test-positive and test-negative groups, the rates of SGA, preterm delivery, duration between maternal symptom onset and delivery, and perinatal complication were not significantly different; but the rate of symptomatic after birth reached significant difference (62.5% vs 20.5%, p = 0.008). CONCLUSIONS: Most neonates born to infected mothers had favorable outcomes. Although direct evidences of intrauterine infection were scarce, the risk of intrauterine infection should be considered based on a positive test in 8.8% of the neonates. Symptomatic neonates born to infected mothers should receive tests for SARS-CoV-2 to initiate appropriate treatment and quarantine. Further studies are warranted to assess the outcomes of COVID-19 in neonates.

COVID-19 in pregnancy: Placental and neonatal involvement.

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 12 million infections and more than 550 000 deaths.1 Morbidity and mortality appear partly due to host inflammatory response.2 Despite rapid, global research, the effect of SARS-CoV-2 on the developing fetus remains unclear. Case reports indicate that vertical transmission is uncommon; however, there is evidence that placental and fetal infection can occur.3-7 Placentas from infected patients show inflammatory, thrombotic, and vascular changes that have been found in other inflammatory conditions.8,9 This suggests that the inflammatory nature of SARS-CoV-2 infection during pregnancy could cause adverse obstetric and neonatal events. Exposure to intrauterine inflammation and placental changes could also potentially result in long-term, multisystemic defects in exposed infants. This review will summarize the known literature on the placenta in SARS-CoV-2 infection, evidence of vertical transmission, and possible outcomes of prenatal exposure to the virus.

Possible intrauterine SARS-CoV-2 infection: Positive nucleic acid testing results and consecutive positive SARS-CoV-2-specific antibody levels within 50 days after birth.

Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the fetus in utero is important to the well-being of the mother and neonate. We report the case of a full-term neonate born to a mother who developed symptoms of coronavirus disease 2019 (COVID-19) at 32 weeks of gestation. The placental pathology showed slight local inflammation. Serial quantitative antibody measurements in the neonate showed elevated levels of IgM on the day of birth and a gradual decline to negative levels within 28 days of life; the levels of IgG declined gradually, but IgG was still positive on day 50 of life. The sequential dynamic changes in antibody levels in the neonate were consistent with those in his mother. One-step reverse transcriptase droplet digital PCR testing for SARS-CoV-2 nucleic acid in throat and anal swabs showed positive results (750 and 892copies/ml) on day 7 of life and negative results on day 14 of life. The neonate had no symptoms of COVID-19. This report enables us to re-evaluate the significance of IgM detection in intrauterine SARS-CoV-2 infection and presents a favorable prognosis for the neonate with long-term exposure to maternal COVID-19, despite a high possibility of intrauterine infection.

Is SARS-CoV-2 Vertically Transmitted?

At the end of 2019, in Wuhan (China), the onset of a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed. The disease, named COVID-19, has a wide spectrum of clinical presentations, ranging from asymptomatic or mild to critical, and for some patients the disease is even fatal. Apparently, being a child or being pregnant does not represent an additional risk for adverse outcomes. The purpose of this mini-review was to investigate what is in the scientific literature, so far, in regard to vertical transmission of SARS-CoV-2. Data were obtained independently by the two authors, who carried out a systematic search in the PubMed, Embase, LILACS, Cochrane, Scopus and SciELO databases using the Medical Subject Heading terms "coronavirus," "COVID-19," and "vertical transmission." Few studies about the vertical transmission of SARS-CoV-2 are found in the literature. In all case reports and case series, the mothers' infection occurred in the third trimester of pregnancy, there were no maternal deaths, and most neonates had a favorable clinical course. The virus was not detected in the neonate nasopharyngeal swab samples at birth, in the placenta, in the umbilical cord, in the amniotic fluid, in the breast milk or in the maternal vaginal swab samples in any of these articles. Only three papers reported neonatal SARS-CoV-2 infection, but there is a bias that positive pharyngeal swab samples were collected at 36 h and on the 2nd, 4th, and 17th days of life. The possibility of intrauterine infection has been based mainly on the detection of IgM and IL-6 in the neonates' serum. In conclusion, to date, no convincing evidence has been found for vertical transmission of SARS-CoV-2.

Asymptomatic COVID-19 infection in late pregnancy indicated no vertical transmission.

This study is to investigate the clinical characteristics of late pregnancy with asymptomatic 2019 novel coronavirus disease (COVID-19) infection, evaluate the outcome of maternal and fetal prognosis, and identify the evidence of intrauterine vertical transmission. A 22-years-old pregnant woman with asymptomatic COVID-19 infection who was admitted to our hospital on 11 February 2020 was enrolled in this study. Clinical data including laboratory test results and chest computed tomography (CT) scanning were collected and reviewed. Diagnosis of late pregnancy with asymptomatic COVID-19 infection was made. Lumbar anesthesia for cesarean section was performed and a female baby was delivered uneventfully, with the Apgar score of 9 to 10 points. Three times of COVID-19 nucleic acid test for the baby was negative after delivery. The puerpera returned to normal after the operation and two times of throat swab COVID-19 nucleic acid test were all negative after antiviral therapy. We reported an asymptomatic COVID-19 pregnant woman with detailed clinical information and our result indicated that for late pregnant women with asymptomatic COVID-19 infection, there might be no intrauterine infection caused by vertical transmission.