The impact of the novel coronavirus infection COVID-19 on the mother-placenta-fetus system

Abstract

Impaired placental development during early pregnancy associated with systemic damage to the vascular endothelium in patients with COVID-19 may result in a number of complications. The study was aimed to reveal histological and immunohistochemical (IHC) features of placental tissue in pregnant women with COVID-19 at different stages of gestation, and to examine the contribution of those to pathogenesis of the disease involving mother-placenta-fetus system. The following two groups of pregnant women were studied: index group of 66 patients with COVID-19, and comparison group of 40 women with no symptoms of viral infection. Macroscopic and microscopic examination, and the IHC analysis of placental samples were carried out. Clinical and anamnestic characteristics of patients with COVID-19 were analyzed taking into account disease severity, delivery route and perinatal outcome. ICH staining using primary antibody revealed elevated expression of proinflammatory factors (TNFα, IL8) and reduced level of anti-inflammatory factors (IL4) in placental structures of patients with moderate and severe СOVID-19 (р < 0.05). The villous tree rearrangement and the development of subclinical placental insufficiency, which could in some cases be decompensated during labor, resulting in clinical manifestations of acute fetal hypoxia were detected in the placental samples obtained from the index group patients. The obstetrical tactics for mothers with COVID-19 should be decided individually based on the risk factors; continuous cardiotocography should be used during labor. It may be appropriate to conduct IHC analysis of placenta in puerperant women with COVID-19 in order to fine-tune the tactics of neonatal management and to predict possible neonatal complications.

Histological Alterations in Placentas of Pregnant Women with SARS-CoV-2 Infection: A Single-Center Case Series

“…Several studies have reported similar findings associated with SARS-CoV-2 infection [24,25]. These findings indicate a placental inflammatory process related to viral invasion, potentially increasing the likelihood of severe maternal and fetal outcomes [33,34]. However, further research is required to establish a direct association with disease severity or progression, particularly concerning transplacental transmission and considering gestational age at the time of infection [35].…”

“…However, the association with maternal or fetal vascular changes remains unclear, as some studies reported similar odds of vascular changes between SARS-CoV-2 infected and healthy individuals [32]. In contrast, others reported increased arteriopathies, hypercapillarization, or villous tree immaturity [33]. In a few cases, these changes were associated with chronic histiocytic intervillositis, membrane hemorrhage, poor placental vascular perfusion, and an increase in perivillous fibrin deposition on the maternal side and occasionally severe outcomes such as fetal death [25].…”

Potential molecular and cellular mechanisms for adverse placental outcomes in pregnancies complicated by SARS-CoV-2 infection—A scoping review

“…However, the neutrophil to macrophage ratio is much higher in early, localized placentitis as compared to diffuse infection [ 33 ]. Infection is also associated with increased levels of inflammatory cytokines including interferon stimulated genes (IFI6, OAS1, CCL3) and proteins (IFNa, IFNy, CCL4), interleukin-10 (IL-10) expression [ 21 ], CXC-motif chemokine ligand 10 (CXCL10) [ 18 , 25 ], tumor necrosis factor alpha (TNFa), CXC-motif chemokine ligand 8 (CXCL8) [ 32 ], interferon gamma-induced protein 10 (IP-10), interferon gamma/ monokine induced by interferon-gamma IFNy/MIG [ 41 ], C-C motif chemokine ligand 3 and 5 (CCL3, CCL5), interleukin-6 (IL-6), interleukin-1-beta (IL1B), interferon alpha (IFNa), and interferon beta (IFNB) [ 35 ] and a decrease in interleukin-4 (IL-4) and macrophage migration inhibitory factor (MIF) expression [ 32 ]. Infection was also associated with an increase in host antiviral effector gene expression including MX dynamin like GTPase 1 (MX1), interferon induced transmembrane protein 1 and 3 (IFITM1, IFITM3), cholesterol 25-hydroxylase (CH25H), toll-like receptor 3 (TLR3), and DExD/ H-box helicase 58 (DDX58) [ 35 ], and increased expression of genes and pathways involved in inflammatory response to viral infection [ 19 ].…”

Stillbirth after COVID-19 in Unvaccinated Mothers Can Result from SARS-CoV-2 Placentitis, Placental Insufficiency, and Hypoxic Ischemic Fetal Demise, Not Direct Fetal Infection: Potential Role of Maternal Vaccination in Pregnancy

“…Extensive intervillous fibrin deposition, involving up to 70% or more of the placental tissues in one case, was present in the placentas from all 5 fetuses. Following this report, additional case reports of the placental pathology from stillborn fetuses delivered to mothers with COVID-19 were reported that showed all the placentas to be markedly abnormal and extensively involved with similar destructive features–increased or massive intervillous fibrin deposition, villous trophoblast necrosis, and chronic histiocytic intervillositis [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. In their report of a stillbirth from a mother having COVID-19 at 30 weeks 4 days gestation in Bratislava, Biringer et al [ 80 ] believed the cause of death to be acute placental insufficiency based upon their findings of placental destruction due to SARS-CoV-2 placentitis and an autopsy revealing fetal organs to have no morphological abnormalities.…”

“…The authors stated that the placental abnormalities were consistent with intense vascular malperfusion which likely resulted in fetal death. A report from Russia described an immunocompromised mother with acute leukemia who developed COVID-19 and delivered a stillborn fetus at 20 weeks of gestation in which there was extensive placental damage causing placental insufficiency and fetal death [ 87 ].…”