SARS-CoV-2 Footprints in the Placenta: What We Know after Three Years of the Pandemic.

As the COVID-19 pandemic continues into its third year, there is accumulating evidence on the consequences of maternal infection. Emerging data indicate increased obstetrics risks, including maternal complications, preterm births, impaired intrauterine fetal growth, hypertensive disorders, stillbirth, gestational diabetes, and a risk of developmental defects in neonates. Overall, controversial concerns still exist regarding the potential for vertical transmission. Histopathological examination of the placenta can represent a useful instrument for investigation and can contribute significant information regarding the possible immunohistopathological mechanisms involved in developing unfavorable perinatal outcomes. Based on current evidence, SARS-CoV-2 infection can affect placental tissue by inducing several specific changes. The level of placental involvement is considered one of the determining factors for unfavorable outcomes during pregnancy due to inflammation and vascular injuries contributing to complex cascade immunological and biological events; however, available evidence does not indicate a strong and absolute correlation between maternal infection, placental lesions, and obstetric outcomes. As existing studies are still limited, we further explore the placenta at three different levels, using histology, immunohistochemistry, and molecular genetics to understand the epidemiological and virological changes observed in the ongoing pandemic.

Pregnancy and COVID-19.

Evidence indicates that SARS-CoV-2 infection increases the likelihood of adverse pregnancy outcomes. Modifications in the circulatory, pulmonary, hormonal, and immunological pathways induced by pregnancy render pregnant women as a high-risk group. A growing body of research shows that SARS-CoV-2 infection during pregnancy is connected to a number of maternal complications, including pneumonia and intensive care unit (ICU) hospitalization. Miscarriages, stillbirth, preterm labor, as well as pre-eclampsia and intrauterine growth restriction are also among the most often documented fetal implications, particularly among expecting women who have significant COVID-19 symptoms, often affecting the timing and route of delivery. Thus, prevention of infection and pharmacological treatment options should aim to minimize the aforementioned risks and ameliorate maternal, obstetric and fetal/neonatal outcomes.

SARS-CoV-2 vertical transmission in a twin-pregnant woman: a case report.

SARS-CoV-2 has affected millions of people around the world in recent years. Among susceptible patients, pregnant women seem to be prone to serious complications. The possibility of SARS-CoV-2 vertical transmission represents one of the most debated topics in the literature, providing inconclusive results. We present a case of a confirmed vertical transmission in a monochorial diamniotic twin pregnancy complicated by a selective intrauterine growth restriction and gestational diabetes mellitus. The analysis of different biological specimens identifies the presence of the SARS-CoV-2 genome in the umbilical cord blood of both twins, and the placental histologic examination confirmed indirect signs of viral infection, supporting the hypothesis that a transplacental infection can occur. Despite the devastating impact that SARS-CoV-2 has worldwide, neonatal infections have been infrequently reported, but they can occur under certain biologic conditions. Deep knowledge of the biological mechanisms underlying the risk of SARS-CoV-2 vertical transmission might be useful to understand the pathophysiological bases and the possible long-term implication of a mother-to-child vertical transmission.

Clinical Manifestation and Obstetric Outcomes in Pregnant Women with SARS-CoV-2 Infection at Delivery: A Retrospective Cohort Analysis.

This retrospective cohort study aimed to analyze the clinical manifestations, complications, and maternal-fetal outcomes in patients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during delivery. The cohort included 61 pregnant women positive for SARS-CoV-2 infection at the time of delivery. Patients were divided into two groups: symptomatic and asymptomatic. We found a significantly higher rate of leukocytosis (p < 0.00078) and lymphopenia (p < 0.0024) in symptomatic women compared with asymptomatic ones. Other laboratory parameters, such as CRP (p = 0.002), AST (p = 0.007), LDH (p = 0.0142), ferritin (p = 0.0036), and D-dimer (p = 0.00124), were also significantly more often increased in the group of symptomatic pregnant women. Overall, symptomatic pregnant women with SARS-CoV-2 infection at the delivery show more often altered laboratory parameters compared with asymptomatic ones; nevertheless, they have a slightly higher but non-significant rate of preterm delivery, cesarean section, as well as lower neonatal birth weight and Apgar score, compared with asymptomatic women.

First-Trimester SARS-CoV-2 Infection: Clinical Presentation, Inflammatory Markers, and Obstetric Outcomes.

OBJECTIVE: Second- and third-trimester SARS-CoV-2 infections may have an increased risk of obstetric complications. However, data on first-trimester infections are scarce. We sought to characterize the clinical and inflammatory presentations and pregnancy outcomes of first-trimester infections. METHODS: A population-based multicenter study including 817 singleton pregnancies with SARS-CoV-2 serologic testing at 8-14 weeks between March and May 2020. Blood count, uterine artery Doppler, and pregnancy-associated plasma protein A (PAPP-A) were performed in all women. Placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), IL-6, and ferritin were determined in positive women. Obstetric outcomes were evaluated. RESULTS: The prevalence of first-trimester infection was 15.2% (n = 124). 72.6% of positive women were asymptomatic. Symptomatic women had higher rates of lymphopenia (1.91 × 109/L vs. 2.16 × 109/L, p = 0.017) and increased levels of IL-6 (9.1% vs. 1.2%, p = 0.051), but lower rates of decreased ferritin (6.3% vs. 19.8%, p = 0.015). PAPP-A was higher in symptomatic women compared with asymptomatic and negative women (1.44 [IQR 0.90-1.82] vs. 1.08 [IQR 0.66-1.61] p = 0.014, vs. 1.08 [IQR 0.77-1.55] p = 0.019, respectively). Obstetric outcomes were not increased. CONCLUSIONS: First-trimester SARS-CoV-2 infections are mostly asymptomatic, with a mild increase of inflammatory markers in symptomatic women. Obstetric complications were not increased, but PAPP-A levels were higher in symptomatic women.

Ethnic Disparities in Coronavirus Disease 2019 after the Implementation of Universal Screening in Hartford, Connecticut.

Objective The aim of this article was to estimate the prevalence of coronavirus disease 2019 (COVID-19) in Connecticut, examine racial/ethnic disparities, and assess pregnancy outcomes in pregnant women following the implementation of universal screening for the virus. Materials and methods This is a retrospective cohort study of all obstetric patients admitted to our labor and delivery unit during the first 4 weeks of implementation of universal screening of COVID-19. Viral studies were performed in all neonates born to mothers with severe acute respiratory syndrome coronavirus 2. We calculated the prevalence of COVID-19, compared the baseline characteristics and pregnancy outcomes between those who tested positive and negative for the virus, and determined the factors associated with COVID-19. Results A total of 10 (4.6%) of 220 women screened positive for the virus. All were asymptomatic. Week 1 had the highest prevalence of infection, nearing 8%. No neonates were infected. Hispanics were more likely to test positive (odds ratio: 10.23; confidence interval: [2.71-49.1], p = 0.001). Obstetric and neonatal outcomes were similar between the groups ( p > 0.05). Conclusion Although the rate of asymptomatic COVID-19 was low, ethnic disparities were present with Hispanics being more likely to have the infection. Key Points 4.6% of pregnant women in labor and delivery tested positive for COVID-19 while being asymptomatic.Hispanic women were more likely to test positive for severe acute respiratory syndrome coronavirus 2.Pregnancy outcomes were similar between COVID-19 positive and negative women.No vertical transmission was detected.

Covid-19 and pregnancy: the experience of a tertiary maternity hospital.

OBJECTIVES: The aim of our study is to present the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and evaluate its impact on maternal and neonatal outcomes. METHODS: We retrospectively reviewed the medical records of all COVID-19 positive pregnant women who were admitted to "Alexandra" maternity hospital from March to December 2020 (n=40). The infection status was determined via real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swab specimen. We documented the demographic features, clinical status, pregnancy characteristics and maternal and fetal outcomes. RESULTS: Forty COVID-19 positive pregnant women were admitted to our clinic during the study period. Mean maternal age was 27.6 years. Gestational age (GA) ranged from 10-42 weeks of pregnancy with mean GA calculated at 38+3 weeks. Associated comorbidities included hypertension, hypothyroidism, epilepsy, hepatitis B and asthma. Thirty-five out of 40 women delivered within the study period. Cesarean section was performed in 57.1% of the cases. Most of the cases (87.5%) were asymptomatic while ventilation was required for only one patient. All neonates tested negative for SARS-CoV-2. Neither maternal nor neonatal deaths occurred. CONCLUSIONS: In alignment to other studies, our data show that the course of coronavirus disease 2019 (COVID-19) during pregnancy in the majority of cases is mild and neonatal outcomes also appear favorable.

Description of a late miscarriage case at 16 Weeks of Gestation associated with a SARS-CoV-2 infection.

BACKGROUND: Data about obstetric complications of maternal infection by SARS-CoV-2 remain sparse. CASE: A 40-year-old pregnant woman, gravida 3 para 1 with no previous obstetric complications, presented a late miscarriage at 16 weeks of gestation on day 9 of COVID-19 disease. The results of her nasopharyngeal swab for SARS-CoV-2, tested the same day, were negative, but the placenta was infected by SARS-CoV-2 and serology was positive 11 days later. No other obstetric or infectious cause was found to explain this outcome. CONCLUSION: This case strongly suggests that SARS-CoV-2 may lead to a late miscarriage.

A pandemic center's experience of managing pregnant women with COVID-19 infection in Turkey: A prospective cohort study.

OBJECTIVE: To evaluate the course and effect of coronavirus disease 2019 (COVID-19) on pregnant women followed up in a Turkish institution. METHODS: A prospective, single tertiary pandemic center cohort study was conducted on pregnant women with confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Positive diagnosis was made on a real-time polymerase chain reaction (RT-PCR) assay of a nasopharyngeal and oropharyngeal specimen. Demographic features, clinical characteristics, and maternal and perinatal outcomes were evaluated. RESULTS: SARS-CoV-2 was suspected in 100 pregnant women. Of them, 29 had the diagnosis confirmed by RT-PCR. Eight of the remaining 71 cases had clinical findings highly suspicious for COVID-19. Ten (34.5%) of the confirmed cases had co-morbidities. Cough (58.6%) and myalgia (51.7%) were the leading symptoms. COVID-19 therapy was given to 10 (34.5%) patients. There were no admissions to the intensive care unit. Pregnancy complications were present in 7 (24.1%) patients. Half of the births (5/10) were cesarean deliveries. None of the neonates were positive for SARS-CoV-2. Samples of breastmilk were also negative for the virus. Three neonates were admitted to the neonatal intensive care unit. CONCLUSION: The clinical course of COVID 19 during pregnancy appears to be mild in the present study.

Pregnancy and COVID-19: a systematic review of maternal, obstetric and neonatal outcomes.

BACKGROUND: There is limited information related to COVID-19 in pregnancy. OBJECTIVES: Evaluate the impact of COVID-19 during pregnancy.Search strategy: Searches were systematically carried out in PubMed, Scopus database and WHO database.Selection criteria: Studies with information related to the effects of COVID-19 in pregnancy, concerning maternal, obstetric, and neonatal outcomes were included.Data collection and analysis: Data were extracted for systematic review following PRISMA guidelines. CARE and STROBE were used to evaluate the quality of data.Main Results: A total of 8 studies involving 95 pregnant women and 51 neonates were included. Overall, the quality was considered good in four studies, moderate in three and poor in one. Among pregnant women, 26% had a history of epidemiological exposure to SARS-CoV-2. The most common symptoms presented were fever (55%), cough (38%) and fatigue (11%). In 50 deliveries, 94% were cesarean sections and 35% were preterm births. Of the 51 neonates, 20% had low birth weight and 1 tested positive for Sars-CoV-2. There was 1 neonatal death, not related to the viral infection, and no cases of severe neonatal asphyxia. CONCLUSIONS: The information compiled in this systematic review may help healthcare providers administer the best possible care.