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Background: Mass administration of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most efficient intervention against the coronavirus disease 2019 (COVID-19) pandemic. Recently, vaccinations were shown to be safe and effective during pregnancy. However, vaccination rates are low in low- and middle-income countries, and vaccine hesitancy is a major limiting factor. Objectives: To investigate the rate of COVID-19 vaccine hesitancy among pregnant women. Method: A cross-sectional questionnaire-based investigation of 313 unvaccinated pregnant women attending an antenatal clinic in Durban, South Africa (SA). The questionnaire included clinical and socio-demographic data, and reasons for vaccine hesitancy were recorded and evaluated. Results: Of 313 women participating, 126 (40.3%) were vaccinated against COVID-19, 21/313 = 6.7%; for those unvaccinated, 21/187 (13.9%) were planning to be vaccinated. However, most unvaccinated women, 174 of 187 (93%), showed COVID-19 vaccine hesitancy. Conclusion: The COVID-19 vaccination hesitancy among pregnant women in Durban, SA, is exceptionally high. This requires urgent attention by the relevant health authorities (both professional health organisations and the SA Department of Health) as many countries experience different waves of the variants of SARS-CoV-2 and herd immunity may not have been achieved. Contribution: This study showed a high vaccine acceptance hesitancy rate among pregnant women in SA.
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Neuropilin-1 (NRP-1) is an essential regulator of maternal immune tolerance, placentation, and angiogenesis. Its dysregulation in preeclampsia (PE) and human immunodeficiency virus (HIV) infection implicates NRP-1 in disease susceptibility and progression. Therefore, this study investigates placental NRP-1 immunoexpression in HIV-complicated preeclamptic pregnancies in South African women of African ancestry receiving antiretroviral therapy. Immunohistochemistry of recombinant anti-neuropilin-1 antibody was performed on placental tissue from 30 normotensive and 60 early onset (EOPE) and late-onset (LOPE) preeclamptic women stratified by HIV status. Qualitative analysis of NRP-1 immunostaining within the chorionic villi revealed a predominant localization in trophoblasts and syncytial knots as well as endothelial, fibroblast-like, and Hofbauer cells. Following morphometric evaluation, we report that PE and HIV infection and/or antiretroviral usage independently downregulate placental NRP-1 immunoexpression; however, as a comorbidity, this decline is further augmented within the conducting and exchange villi. Furthermore, reduced immunoexpression of NRP-1 in EOPE compared with LOPE villi may be due to maternal-fetal maladaptation. It is plausible that the decreased NRP-1 immunoexpression in PE placentae facilitates syncytiotrophoblast apoptosis and subsequent deportation of NRP-1 into the maternal circulation, contributing to the anti-angiogenic milieu of PE. We hypothesize that the intense NRP-1 immunoreactivity observed in Hofbauer cells at the maternal-fetal interface may contribute to the natural prevention mechanism of HIV vertical transmission.
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Infecções por HIV , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Vilosidades Coriônicas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Neuropilina-1 , Placenta , África do Sul , TrofoblastosRESUMO
Successful pregnancy is dependent on implantation, nutrient and gas exchange, as well as fetal protection from the immunologic attack. Placental pathologies and preterm delivery closely correlate with the size and shape of the placenta. Additionally, normal vaginal microbiota is disturbed during viral insults such as SARS-CoV-2 and HIV, with consequent placental anomalies. This chapter focuses on placental development, morphology, and pathology while also investigating placental bed structure and function. Placental anomalies with regard to HIV-1 and SARS-CoV-2 infection and placental morphometric image analysis and its relevance for verification of placental pathology are explored. Since image analysis remains optional for routine diagnostic purposes, authentication of placental appraisal warrants the use of measurable predefined definitions. Immunohistochemical analyses of placental morphology and angiogenic, epithelial, and apoptotic mechanisms facilitate research into etiopathogenetic pathways involved in placental anomalies with a focus on discovering novel diagnostic foci. Thus, image analyses as an adjunct to complement pathological investigations are recommended.
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COVID-19 , Placenta , Gravidez , Humanos , Feminino , SARS-CoV-2 , Placentação , FetoRESUMO
This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.
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Tratamento Farmacológico da COVID-19 , COVID-19 , Infecções por HIV , MicroRNAs , Pré-Eclâmpsia , Feminino , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/genética , COVID-19/complicações , SARS-CoV-2 , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Comorbidade , MicroRNAs/genética , HIVRESUMO
Introduction: This review explores angiogenesis, vascular dysfunction, the complement system, RAAS, apoptosis and NETosis as potential pathways that are dysregulated during preeclampsia, HIV infection and ART usage. Results: HIV-1 accessory and matrix proteins are protagonists for the elevation of oxidative stress, apoptosis, angiogenesis, and elevation of adhesion markers. Despite the immunodeficiency during HIV-1 infection, HIV-1 exploits our cellular defence arsenal by escaping cell-mediated lysis, yet HIV-1 infectivity is enhanced via C5a release of TNF-α and IL-6. This review demonstrates that PE is an oxidatively stressed microenvironment associated with increased apoptosis and NETosis, but with a decline in angiogenesis. Immune reconstitution in the duality of HIV-1 and PE by protease inhibitors, HAART and nucleoside reverse transcriptase, affect similar cellular pathways that eventuate in loss of endothelial cell integrity and, hence, its dysfunction. Conclusions: HIV-1 infection, preeclampsia and ARTs differentially affect endothelial cell function. In the synergy of both conditions, endothelial dysfunction predominates. This knowledge will help us to understand the effect of HIV infection and ART on immune reconstitution in preeclampsia.
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Infecções por HIV/complicações , Pré-Eclâmpsia/metabolismo , Animais , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Apoptose , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/virologia , Armadilhas Extracelulares/metabolismo , Feminino , Humanos , Neovascularização Fisiológica , Estresse Oxidativo , Pré-Eclâmpsia/virologia , GravidezRESUMO
PURPOSE OF REVIEW: This review investigated the potential role of microRNAs (miRNAs) in the synergy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, preeclampsia (PE), and human immunodeficiency virus (HIV) infection. Maternal health is a great concern when treating pregnant women fighting this triad of diseases, which is highly prevalent in South Africa. MicroRNAs are involved in fine-tuning of physiological processes. Disruptions to the balance of this minute protein can lead to various physiological changes that are sometimes pathological. RECENT FINDINGS: MicroRNAs have recently been implicated in PE and have been linked to the anti-angiogenic imbalance evident in PE. Recent in silico studies have identified potential host miRNAs with anti-viral properties against SARS-CoV-2 infection. Studies have demonstrated dysregulated expression of several miRNAs in HIV-1 infection along with the ability of HIV-1 to downregulate anti-viral host microRNAs. This review has highlighted the significant gap in literature on the potential of miRNAs in women with HIV-associated PE in synergy with the novel SARS-CoV-2 infection. In addition, this review has provided evidence of the critical role that the epigenetic regulatory mechanism of miRNA plays in viral infections and PE, thereby providing a foundation for further research investigating the potential of therapeutic miRNA development with fewer side-effects for pregnant women.