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1.
J Microbiol Biotechnol ; 32(9): 1098-1102, 2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-2144003

ABSTRACT

The placenta is a captivating multifunctional organ of fetal origin and plays an essential role during pregnancy by intimately connecting mother and baby. This study explicates placental pathology and information about 25 placentas collected from the mothers infected with novel coronavirus (SARS-COV-2). So far, congenital transmission of SARS-CoV-2 seems to be remarkably uncommon in spite of many cases of COVID-19 during pregnancy. Out of the 25 placental tissue samples collected, none has shown gene expression of SARS-CoV-2 when confirmed by RT-PCR. At the same time, nasal and throat swab samples collected from newborns of SARS-CoV-2-positive mothers correspondingly tested negative by RT-PCR. The shielding properties of placental barriers against viral infections from mothers to newborns remains a mystery. Major histopathological findings have been recorded as choriodecidual tissue with necrosis, intramural fibrin deposition, chorionic villi with fibrosis, and calcification. Moreover, although recent findings are insufficient to prove direct placental transmission of COVID-19, the abundance of angiotensin-converting enzymes-2 (ACE-2) on the placental surface could potentially contribute to unpleasant outcomes during pregnancy as SARSCoV-2 gains access to human cells via ACE-2. Finally, the significance of these findings is vague and needs further study.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Angiotensins , Female , Fibrin , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Mothers , Placenta/pathology , Pregnancy , SARS-CoV-2
2.
Indian J Pathol Microbiol ; 65(4): 860-863, 2022.
Article in English | MEDLINE | ID: covidwho-2100025

ABSTRACT

Background: SARS-CoV-2 has emerged as a major pandemic of the century and little is known about the impact of maternal infection on placental histopathology. Histopathologic examination of placental tissue can contribute to significant information regarding the pathophysiology of the disease and how it affects the fetal outcome. Materials and Methods: This was a cross-sectional study conducted at the Department of Pathology, Government Doon Medical College and Hospital, Dehradun, on the placenta of 50 coronavirus disease 2019 (COVID-19)-positive pregnant females confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) from August 2020 to October 2020. Fifty term historical placentas were taken as control. Placenta sections were fixed in formalin, processed into paraffin blocks, stained with hematoxylin and eosin (H and E) stain, and visualized for any abnormality. Results: The most prominent histological finding in the placenta of pregnant women affected by COVID-19 was chorangiosis, which is a feature of fetal vascular malperfusion seen in 28 (56%) cases. Other features included maternal vascular malperfusions (MVM) such as villous crowding and agglutination in 12 (24%) cases. Tenney-Parker change was seen in 13 (26%) patients. Intervillous fibrinoid deposition and intervillous hemorrhage were seen in 37 (74%) patients and 7 (14%) patients showed significant calcification. Other findings observed were less common. Conclusion: Infection with SARS-CoV-2 may be associated with a significant impact on fetal and maternal circulation causing features of fetal and maternal malperfusion such as chorangiosis, villous crowding, and agglutination. Indicating that the infection could cause a potential rise in the risk of adverse perinatal outcomes such as intrauterine fetal growth retardation, preterm birth, or stillbirth.


Subject(s)
COVID-19 , Placenta Diseases , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Infant, Newborn , Pregnancy , SARS-CoV-2 , Placenta/pathology , Cross-Sectional Studies , Premature Birth/pathology , Fetal Growth Retardation , Placenta Diseases/pathology
3.
PLoS Negl Trop Dis ; 16(10): e0010898, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2098682

ABSTRACT

Rift Valley fever (RVF) is a disease of animals and humans associated with abortions in ruminants and late-gestation miscarriages in women. Here, we use a rat model of congenital RVF to identify tropisms, pathologies, and immune responses in the placenta during vertical transmission. Infection of late-gestation pregnant rats resulted in vertical transmission to the placenta and widespread infection throughout the decidua, basal zone, and labyrinth zone. Some pups from infected dams appeared normal while others had gross signs of teratogenicity including death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had widespread hemorrhage throughout multiple placenta layers. Teratogenic events were associated with significant increases in placental pro-inflammatory cytokines, type I interferons, and chemokines. RVFV displays a high degree of tropism for all placental tissue layers and the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. Given the potential for RVFV to emerge in new locations and the recent evidence of emerging viruses, like Zika and SARS-CoV-2, to undergo vertical transmission, this study provides essential understanding regarding the mechanisms by which RVFV crosses the placenta barrier.


Subject(s)
COVID-19 , Rift Valley Fever , Rift Valley fever virus , Zika Virus Infection , Zika Virus , Humans , Female , Pregnancy , Rats , Animals , Rats, Sprague-Dawley , Placenta/pathology , SARS-CoV-2 , Ruminants
4.
Viruses ; 14(9)2022 09 14.
Article in English | MEDLINE | ID: covidwho-2043973

ABSTRACT

There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases (n = 2), whereas 92% of cases were negative (n = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted (n = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal-neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/diagnosis , Female , Humans , Immunoglobulin G , Immunoglobulin M , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2
5.
Placenta ; 128: 23-28, 2022 10.
Article in English | MEDLINE | ID: covidwho-2004415

ABSTRACT

INTRODUCTION: Placental alterations caused by severe acute respiratory coronavirus-2 (SARS-CoV-2) infection have already been described, but most studies used small sample groups and the difference according to the severity of the disease has not been verified. Our objective was to describe placental alterations in patients with coronavirus disease 2019 (COVID-19) and analyze the association of pathological placental findings with the clinical parameters of COVID-19 and perinatal results. METHODS: This was a nested study within a prospective cohort study involving 109 symptomatic pregnant women with COVID-19. The prevalence of observed placental alterations was described, and the associations of pathological findings with the clinical parameters of COVID-19 severity and with perinatal outcomes were assessed. RESULTS: The frequency of types of placental features was poor maternal vascular perfusion in 45% of cases, poor fetal vascular perfusion in 33.9%, hematogenous origin infection in 32.1%, and morphological changes corresponding to ascending infection in 21.1%. Hematogenous infection differed significantly according to COVID-19 severity (p = 0.008), with a prevalence ratio (PR) of 1.74 (95% confidence interval, 1.02-2.98) in the moderate COVID-19 group compared to the mild COVID-19 group. Among the perinatal outcomes, there was an unexpected inverse association between prematurity and placental infection of hematogenous origin, with lower rates of prematurity among cases with inflammation of hematogenous origin (p = 0.029). DISCUSSION: Moderate SARS-Cov-2 infection presented a higher prevalence of placental pathological findings. There was no association of placental findings with adverse perinatal outcomes.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Prospective Studies , SARS-CoV-2
6.
Infect Dis Obstet Gynecol ; 2022: 8061112, 2022.
Article in English | MEDLINE | ID: covidwho-2001964

ABSTRACT

Background: Vertical transmission of several viruses during pregnancy has been shown to cause adverse fetal outcomes. The question about the possibility of a similar outcome in association with SARS-CoV-2 has been raised in recently published articles. Indeed, the rate of transmission through the placenta to the fetus reported in women with COVID-19 has been shown to form a minority. The aim of this study was to explore the possible histopathological changes in the placenta of pregnant women with COVID-19 after delivery and those changes in the umbilical cord. Methods: A case-control study including a total of 50 full-term pregnant women with COVID-19 and 60 control pregnant females. Histopathological evaluation of placental tissues and umbilical cords were reported. Results: The main findings in the umbilical cord were increased thickness of vessels, thrombus formation, endothelins, and narrow lumen; except for the increased thickness of blood vessels, these findings were more frequently seen in women with COVID-19, in comparison with control women in a significant manner (p < 0.05). Increased thickness of blood vessels was more significantly observed in the control group compared to the COVID-19 group (p < 0.01). Findings of the placenta included avascular villi, fibrin, thrombosis, and meconium macrophage in various combinations. Except for fibrin as the sole findings, all other findings including combinations were more frequently encountered in the study group in comparison to the control group (p < 0.05). Conclusion: Pregnant women with COVID-19 have significant pathological alterations in the placenta and umbilical cord. These findings reflect the capability of SARS-CoV-2 in causing immunological reactions to the placenta, either directly or indirectly, and these pathologies may be linked to the higher rate of adverse neonatal outcomes and maternal admission to the intensive care unit.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Case-Control Studies , Female , Fibrin , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Pregnant Women , SARS-CoV-2
7.
Viruses ; 14(6)2022 06 18.
Article in English | MEDLINE | ID: covidwho-1964107

ABSTRACT

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a "barrier" to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms' severity was related to different placental histological characteristics and the immune microenvironment, we subdivided 29 placentas from 29 mothers positive for SARS-CoV-2 into two groups, depending on the symptomatology (moderate/severe vs. asymptomatic/mild), performing immunohistochemical investigations for CD4 + and CD8 + T lymphocytes, as well as for CD68 + macrophage. We also evaluated the immuno-expression of the ACE2 receptor at the placental level. These two groups were compared to a control group of 28 placentas from 28 SARS-CoV-2-negative healthy mothers. (3) Results: The symptoms (likely to be related to viremia) were statistically significantly correlated (p < 0.05) with histopathological changes, such as maternal malperfusion, decidual arteriopathy, blood vessel thrombus of fetal relevance. Furthermore, the immuno-expression of ACE2 was significantly lower in SARS-CoV-2-positive groups vs. control group (p = 0.001). (4) Conclusions: There is still much to study and discover regarding the relationship between SARS-CoV-2 and histological changes in placentas and how the latter might contribute to various neonatal clinical outcomes, such as prematurity.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Angiotensin-Converting Enzyme 2 , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , SARS-CoV-2
8.
Placenta ; 127: 1-7, 2022 09.
Article in English | MEDLINE | ID: covidwho-1937084

ABSTRACT

INTRODUCTION: This study aims at observing placental pathologies in COVID-19 infected women, and analyzing its impact on pregnancy outcome. METHOD: This is a descriptive-analytical study done at a tertiary centre of Northern India. All COVID-19 positive pregnant women with gestational age ≥20 weeks, with placental histopathological reporting, were included in this study. A total of 173 COVID-19 pregnant women were included in the study. RESULTS: Placental abnormalities were noticed in 49·16% of total 179 placentae examined. Maternal vascular malperfusion (27·93%) was the most observed placental pathology followed by villous fibrin deposits (22·90%), fetal vasculopathy (16·75%), and acute inflammation (6·70%). Stillbirths were 22 and NICU admissions were seen in 50 neonates. Abnormal placental abnormalities led to higher stillbirths (p value 0·011) and lower Apgar scores at 1 and 5 min (p-value 0·028; p-value 0·002, respectively). Intervillous fibrin deposits had higher risk associated with lower Apgar score at 1 and 5 min [RR 2·05 (95% CI 1·21-3·48, p-value 0·010) and RR 5·52 (95% CI 2·58-11·81, p-value <0·001), respectively]. RP clot/hemorrhage was also associated with lower Apgar score at 1 and 5 min [RR 2·61 (95% CI 1·52-4·49, p-value 0·002) and RR 3.54 (95% CI 1·66-7·55, p-value 0·001), respectively]. DISCUSSION: Placental abnormalities in COVID-19 infection were associated with significant higher incidence of unexplained stillbirths, and lower Apgar scores. Although, this is the largest descriptive-analytical study done so far, comparative studies are required to draw a clear conclusion regarding the impact of COVID-19 infection on human placenta and its effect on pregnancy outcomes.


Subject(s)
COVID-19 , Placenta Diseases , Pregnancy Complications, Infectious , Female , Fibrin , Humans , Infant , Infant, Newborn , Mothers , Placenta/pathology , Placenta Diseases/pathology , Pregnancy , Pregnancy Outcome , Stillbirth/epidemiology
9.
BMC Pregnancy Childbirth ; 21(1): 760, 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1923523

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn. CASE PRESENTATION: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma. CONCLUSIONS: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Placenta/pathology , Pregnancy Complications, Infectious/therapy , Adult , COVID-19/diagnosis , Cesarean Section , Female , Humans , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Trimester, Second , Treatment Outcome
10.
Placenta ; 126: 125-132, 2022 08.
Article in English | MEDLINE | ID: covidwho-1914907

ABSTRACT

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Antibodies, Viral , Female , Humans , Immunoglobulin G , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2 , Trophoblasts/pathology
11.
Surg Pathol Clin ; 15(2): 175-196, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1900072

ABSTRACT

The Amsterdam Placental Workshop Group Consensus Statement on Sampling and Definitions of Placental Lesions has become widely accepted and is increasingly used as the universal language to describe the most common pathologic lesions found in the placenta. This review summarizes the most salient aspects of this seminal publication and the subsequent emerging literature based on Amsterdam definitions and criteria, with emphasis on publications relating to diagnosis, grading, and staging of placental pathologic conditions. We also provide an overview of the recent expert recommendations on the pathologic grading of placenta accreta spectrum, with insights on their clinical context. Finally, we discuss the emerging entity of SARS-CoV2 placentitis.


Subject(s)
COVID-19 , Placenta , Consensus , Female , Humans , Placenta/pathology , Pregnancy , RNA, Viral , SARS-CoV-2
12.
Arch Pathol Lab Med ; 146(6): 660-676, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1876076

ABSTRACT

CONTEXT.­: Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. OBJECTIVE.­: To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN.­: Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. RESULTS.­: Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. CONCLUSIONS.­: The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths.


Subject(s)
COVID-19 , Perinatal Death , Placenta , Pregnancy Complications, Infectious , COVID-19/complications , Female , Fibrin , Humans , Hypoxia/pathology , Hypoxia/virology , Infant, Newborn , Infectious Disease Transmission, Vertical , Perinatal Death/etiology , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/mortality , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , Retrospective Studies , SARS-CoV-2 , Stillbirth
13.
Am J Perinatol ; 39(15): 1643-1653, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1873578

ABSTRACT

We aimed to perform a meta-analysis of the literature concerning histopathologic findings in the placentas of women with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection during pregnancy. Searches for articles in English included PubMed, Web of Science, Google Scholar, and reference lists (up to April 2021). Studies presenting data on placental histopathology according to the Amsterdam Consensus Group criteria in SARS-CoV-2 positive and negative pregnancies were identified. Lesions were categorized into: maternal and fetal vascular malperfusion (MVM and FVM, respectively), acute placental inflammation with maternal and fetal inflammatory response (MIR and FIR, respectively), chronic inflammatory lesions (CILs), and increased perivillous fibrin deposition (PVFD). A total of 15 studies reporting on 19,025 placentas, n = 699 of which were derived from women who were identified as being infected with SARS-CoV-2 and 18,326 as SARS-CoV-2-negative controls, were eligible for analysis. No significant difference in incidence of MVM (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 0.73-1.90), FVM (OR: 1.23, 95% CI: 0.63-2.42), MIR (OR: 0.66, 95% CI: 0.29-1.52) or FIR (OR: 0.85, 95% CI: 0.44-1.63), and CILs (OR: 0.97, 95% CI: 0.55-1.72) was found between placentae from gravida identified as being SARS-CoV-2 infected. However, placenta from gravida identified as being infected with SARS-CoV-2 were associated with significantly increased occurrence of PVFD (OR: 2.77, 95% CI: 1.06-7.27). After subgroup analyses based on clinical severity of COVID-19 infection, no significant difference was observed in terms of reported placental pathology between symptomatic or asymptomatic SARS-CoV-2 gravidae placenta. Current evidence based on the available literature suggests that the only pathologic finding in the placentae of women who are pregnant identified as having been infected with SARS-CoV-2 was an increased prevalence of PVFD. KEY POINTS: · No association between SARS-CoV-2 and maternal or fetal placental malperfusion.. · No association between SARS-CoV-2 and maternal or fetal inflammatory response.. · SARS-CoV-2 is associated with increased perivillous fibrin deposition in placenta..


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Pregnancy , COVID-19/epidemiology , Fibrin , Inflammation/pathology , Placenta/pathology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , SARS-CoV-2
15.
Front Immunol ; 13: 825075, 2022.
Article in English | MEDLINE | ID: covidwho-1834402

ABSTRACT

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.


Subject(s)
Abortion, Habitual , COVID-19 , Chorioamnionitis , Abortion, Habitual/etiology , Abortion, Habitual/pathology , Chorioamnionitis/pathology , Chronic Disease , Female , Fetal Death/etiology , Fetal Growth Retardation/etiology , Fetal Growth Retardation/pathology , Fibrin , Humans , Placenta/pathology , Pregnancy , Pregnancy Outcome , SARS-CoV-2 , Syndrome
16.
Placenta ; 123: 12-23, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1815047

ABSTRACT

INTRODUCTION: The effect of SARS-CoV-2 severity or the trimester of infection in pregnant mothers, placentas, and infants is not fully understood. METHODS: A retrospective, observational cohort study in Chapel Hill, NC of 115 mothers with SARS-CoV-2 and singleton pregnancies from December 1, 2019 to May 31, 2021 via chart review to document the infants' weight, length, head circumference, survival, congenital abnormalities, hearing loss, maternal complications, and placental pathology classified by the Amsterdam criteria. RESULTS: Of the 115 mothers, 85.2% were asymptomatic (n = 37) or had mild (n = 61) symptoms, 13.0% had moderate (n = 9) or severe (n = 6) COVID-19, and 1.74% (n = 2) did not have symptoms recorded. Moderate and severe maternal infections were associated with increased C-section, premature delivery, infant NICU admission, and were more likely to occur in Type 1 (p = 0.0055) and Type 2 (p = 0.0285) diabetic mothers. Only one infant (0.870%) became infected with SARS-CoV-2, which was not via the placenta. Most placentas (n = 63, 54.8%) did not show specific histologic findings; however, a subset showed mild maternal vascular malperfusion (n = 26, 22.6%) and/or mild microscopic ascending intrauterine infection (n = 28, 24.3%). The infants had no identifiable congenital abnormalities, and all infants and mothers survived. DISCUSSION: Most mothers and their infants had a routine clinical course; however, moderate and severe COVID-19 maternal infections were associated with pregnancy complications and premature delivery. Mothers with pre-existing, non-gestational diabetes were at greatest risk of developing moderate or severe COVID-19. The placental injury patterns of maternal vascular malperfusion and/or microscopic ascending intrauterine infection were not associated with maternal COVID-19 severity.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Premature Birth , Female , Humans , Immunoglobulin G , Infant , Infectious Disease Transmission, Vertical , Mothers , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Premature Birth/epidemiology , Premature Birth/pathology , Retrospective Studies , SARS-CoV-2
17.
Hum Pathol ; 125: 18-22, 2022 07.
Article in English | MEDLINE | ID: covidwho-1778168

ABSTRACT

Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure without infection has been well described. However, whether the characteristic placental pathology persists after the acute phase of the infection is less clear. We retrospectively identified 67 COVID-19-recovered pregnant patients who had placental pathology available. After reviewing the gross and histopathology, we categorized the findings and studied the placentas for evidence of chronic infection by immunohistochemistry for the spike protein of the virus. We found these placentas showed significantly increased prevalence of maternal and a trend towards significance of fetal vascular malperfusion when compared to a control group of placentas examined for the sole indication of maternal group B streptococcal colonization. None of the COVID-19-recovered placentas showed expression of the viral spike protein; therefore, we found no evidence of persistent infection of the placenta in women with a history of COVID-19 during their pregnancy. We conclude that recovery from a SARS-CoV-2 infection during pregnancy puts the pregnancy at risk for specific pathology.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Retrospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
18.
Front Immunol ; 13: 861245, 2022.
Article in English | MEDLINE | ID: covidwho-1775684

ABSTRACT

Pregnancy can be defined a vascular event upon endocrine control. In the human hemo-chorial placentation the chorionic villi penetrate the wall of the uterine spiral arteries, to provide increasing amounts of nutrients and oxygen for optimal fetal growth. In any physiological pregnancy the natural maternal response is of a Th1 inflammatory type, aimed at avoiding blood loss through the arteriolar wall openings. The control of the vascular function, during gestation as in any other condition, is achieved through the action of two main types of prostanoids: prostaglandin E2 and thromboxane on the one hand (for vasoconstriction and coagulation), prostacyclin on the other (for vasodilation and blood fluidification). The control of the maternal immune response is upon the responsibility of the fetus itself. Indeed, the chorionic villi are able to counteract the natural maternal response, thus changing the inflammatory Th1 type into the anti-inflammatory Th2. Clinical and experimental research in the past half century address to inflammation as the leading cause of abortion, pregnancy loss, premature delivery and related pulmonary, cerebral, intestinal fetal syndromes. Increased level of Interleukin 6, Interleukin 1-beta, Tumor Necrosis Factor-alfa, Interferon-gamma, are some among the well-known markers of gestational inflammation. On the other side, COVID-19 pneumonia is a result of extensive inflammation induced by viral replication within the cells of the respiratory tract. As it may happen in the uterine arteries in the absence of an effective fetal control, viral pneumonia triggers pulmonary vascular coagulation. The cytokines involved in the process are the same as those in gestational inflammation. As the fetus breathes throughout the placenta, fetal death from placental thrombosis is similar to adult death from pulmonary thrombosis. Preventing and counteracting inflammation is mandatory in both conditions. The most relevant literature dealing with the above-mentioned concepts is reviewed in the present article.


Subject(s)
Abortion, Spontaneous , COVID-19 , Thrombosis , Abortion, Spontaneous/pathology , Adult , Cytokines , Female , Humans , Inflammation/pathology , Placenta/pathology , Pregnancy , Thrombosis/pathology
19.
Ultrasound Obstet Gynecol ; 59(6): 813-822, 2022 06.
Article in English | MEDLINE | ID: covidwho-1763301

ABSTRACT

OBJECTIVES: To describe the placental pathology, fetal autopsy findings and clinical characteristics of pregnancies that resulted in stillbirth owing to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, and to identify potential risk factors. METHODS: This was a prospective multicenter study of non-vaccinated pregnant women affected by coronavirus disease 2019 (COVID-19) in Greece from April 2020 to August 2021. A total of 165 placentas were examined histologically and six cases of stillbirth associated with SARS-CoV-2 placentitis were retrieved. Complete fetal autopsy was performed in three of these cases. Gross, histopathological, immunohistochemical, molecular and electron microscopy examinations were carried out in the stillbirth placentas and fetal organs. The histological findings of cases with SARS-CoV-2 placentitis were compared with those in 159 cases with maternal COVID-19 which resulted in a live birth. Regression analysis was used to identify predisposing risk factors for SARS-CoV-2 placentitis. RESULTS: The placentas of all six stillborn cases showed severe and extensive histological changes typical of SARS-CoV-2 placentitis, characterized by a combination of marked intervillositis with a mixed inflammatory infiltrate and massive perivillous fibrinoid deposition with trophoblast damage, associated with intensely positive immunostaining for SARS-CoV-2 spike protein, the presence of virions on electron microscopy and positive reverse-transcription polymerase chain reaction test of placental tissues. The histological lesions obliterated over 75% of the maternal intervillous space, accounting for intrauterine fetal death. Similar histological lesions affecting less than 25% of the placenta were observed in seven liveborn neonates, while the remaining 152 placentas of COVID-19-affected pregnancies with a live birth did not show these findings. Complete fetal autopsy showed evidence of an asphyctic mode of death without evidence of viral transmission to the fetus. The mothers had mild clinical symptoms or were asymptomatic, and the interval between maternal COVID-19 diagnosis and fetal death ranged from 3 to 15 days. Statistically significant predisposing factors for SARS-CoV-2 placentitis included thrombophilia and prenatally diagnosed fetal growth restriction (FGR). Multiple sclerosis was seen in one case. CONCLUSIONS: SARS-CoV-2 placentitis occurred uncommonly in COVID-19-affected pregnancies of non-vaccinated mothers and, when extensive, caused fetal demise, with no evidence of transplacental fetal infection. Thrombophilia and prenatally detected FGR emerged as independent predisposing factors for the potentially lethal SARS-CoV-2 placentitis. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
COVID-19 , Chorioamnionitis , Pregnancy Complications, Infectious , Thrombophilia , COVID-19 Testing , Female , Fetal Death/etiology , Fetus/pathology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Prospective Studies , Risk Factors , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Stillbirth/epidemiology , Thrombophilia/complications , Thrombophilia/pathology
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