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Article ; Online: Being Pregnant during the Kivu Ebola Virus Outbreak in DR Congo

David A. Schwartz

Vaccines, Vol 8, Iss 1, p

The rVSV-ZEBOV Vaccine and Its Accessibility by Mothers and Infants during Humanitarian Crises and in Conflict Areas

2020 Volume 38

Abstract: The Ebola virus disease (EVD) outbreak that began in Kivu province of the Democratic Republic of the Congo (DRC) in July 2018 is the second largest in history. It is also the largest and most deadly of the ten Ebola outbreaks to occur in DRC, the country ...

Abstract	The Ebola virus disease (EVD) outbreak that began in Kivu province of the Democratic Republic of the Congo (DRC) in July 2018 is the second largest in history. It is also the largest and most deadly of the ten Ebola outbreaks to occur in DRC, the country where Ebola was first identified during the 1976 Yambuku outbreak. The Kivu region is one of the most challenging locations in which to organize humanitarian assistance. It is an active conflict zone in which numerous armed groups are conducting violent acts, often directed against the inhabitants, healthcare and relief workers and peacekeepers. EVD has been especially problematic in pregnancy—previous outbreaks both in DRC and other countries have resulted in very high mortality rates among pregnant women and especially their infants, with maternal mortality in some outbreaks reaching over 90% and perinatal mortality 100%. The development and implementation of the Merck rVSV-ZEBOV vaccine for Ebola infection has been a tremendous public health advance in preventing EVD, being used successfully in both the West Africa Ebola epidemic and the Équateur DRC Ebola outbreak. But from the start of the Kivu outbreak, policy decisions had resulted in excluding pregnant and lactating women and their infants from receiving it during extensive ring vaccination efforts. In June 2019, this policy was reversed, 10 months after the start of the outbreak. Pregnant and lactating women are now permitted not only the rVSV-ZEBOV vaccine in the continuing Kivu outbreak but also the newly implemented Ad26.ZEBOV/MVA-BN vaccine.
Keywords	ebola virus ; ebola vaccine ; democratic republic of the congo ; pregnancy ; maternal death ; rvsv-zebov ; vaccination ; hemorrhagic fever ; excluding pregnant women ; epidemic ; filovirus ; clinical trial ; vaccinating pregnant women ; humanitarian crisis ; clinical trials ; conflict area ; Medicine ; R
Subject code	390
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical Trials and Administration of Zika Virus Vaccine in Pregnant Women

David A. Schwartz

Vaccines, Vol 6, Iss 4, p

Lessons (that Should Have Been) Learned from Excluding Immunization with the Ebola Vaccine during Pregnancy and Lactation

2018 Volume 81

Abstract: As evidenced from recent epidemics, both Ebola and Zika virus infection are potentially catastrophic when occurring in pregnant women. Ebola virus causes extremely high rates of mortality in both mothers and infants; Zika virus is a TORCH infection that ... ...

Abstract	As evidenced from recent epidemics, both Ebola and Zika virus infection are potentially catastrophic when occurring in pregnant women. Ebola virus causes extremely high rates of mortality in both mothers and infants; Zika virus is a TORCH infection that produces a congenital malformation syndrome and pediatric neurodevelopmental abnormalities. Production of efficacious vaccines has been a public health priority for both infections. Unfortunately, during the clinical trials and subsequent deployment of a vaccine for the Ebola virus, pregnant and lactating women were, and continue to be, excluded from receiving the life-saving vaccine. The most serious consequence of Zika virus infection, congenital Zika syndrome, results from fetal infection during pregnancy. Thus, pregnant women have a major stake in the ongoing development of a vaccine for Zika virus. The exclusion of pregnant women from the development, clinical trials and administration of a potential Zika vaccine unfairly deprives them and their infants of the protection they need against this potentially catastrophic intrauterine infection. When creating policy about these issues, it is important to critically evaluate vaccine safety in pregnancy in the context of the substantial risk of infection for the pregnant woman and her fetus in the absence of immunization.
Keywords	Zika virus ; vaccine ; Zika vaccine ; congenital Zika syndrome ; pregnancy ; Ebola virus ; Ebola vaccine ; women’s rights ; clinical trials ; epidemic ; vaccination ; congenital infections ; exclusion pregnant women ; Medicine ; R
Subject code	610
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Characterizing COVID-19 maternal-fetal transmission and placental infection using comprehensive molecular pathology

David A. Schwartz / Kristen M. Thomas

EBioMedicine, Vol 60, Iss , Pp 102983- (2020)

2020

Keywords	Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Potential Maternal and Infant Outcomes from Coronavirus 2019-nCoV (SARS-CoV-2) Infecting Pregnant Women

David A. Schwartz / Ashley L. Graham

Viruses, Vol 12, Iss 2, p

Lessons from SARS, MERS, and Other Human Coronavirus Infections

2020 Volume 194

Abstract: In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified ... ...

Abstract	In early December 2019 a cluster of cases of pneumonia of unknown cause was identified in Wuhan, a city of 11 million persons in the People’s Republic of China. Further investigation revealed these cases to result from infection with a newly identified coronavirus, initially termed 2019-nCoV and subsequently SARS-CoV-2. The infection moved rapidly through China, spread to Thailand and Japan, extended into adjacent countries through infected persons travelling by air, eventually reaching multiple countries and continents. Similar to such other coronaviruses as those causing the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), the new coronavirus was reported to spread via natural aerosols from human-to-human. In the early stages of this epidemic the case fatality rate is estimated to be approximately 2%, with the majority of deaths occurring in special populations. Unfortunately, there is limited experience with coronavirus infections during pregnancy, and it now appears certain that pregnant women have become infected during the present 2019-nCoV epidemic. In order to assess the potential of the Wuhan 2019-nCoV to cause maternal, fetal and neonatal morbidity and other poor obstetrical outcomes, this communication reviews the published data addressing the epidemiological and clinical effects of SARS, MERS, and other coronavirus infections on pregnant women and their infants. Recommendations are also made for the consideration of pregnant women in the design, clinical trials, and implementation of future 2019-nCoV vaccines.
Keywords	coronavirus ; middle east respiratory syndrome ; severe acute respiratory syndrome ; sars-cov ; mers-cov ; wuhan coronavirus ; 2019-ncov ; sars-cov-2 ; covid-19 ; pregnancy ; maternal mortality ; maternal death ; pregnancy complications ; maternal morbidity ; pneumonia ; epidemic ; emerging infection ; china ; wuhan coronavirus outbreak ; Microbiology ; QR1-502 ; covid19
Subject code	610
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

David A. Schwartz / Mattia Bugatti / Amerigo Santoro / Fabio Facchetti

Journal of Developmental Biology, Vol 9, Iss 33, p

2021 Volume 33

Abstract: A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can ... ...

Abstract	A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.
Keywords	SARS-CoV-2 ; placental pathology ; cytotrophoblast ; syncytiotrophoblast ; COVID-19 ; pregnancy ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inhibition of antiapoptotic BCL-2 proteins with ABT-263 induces fibroblast apoptosis, reversing persistent pulmonary fibrosis

Joseph C. Cooley / Nomin Javkhlan / Jasmine A. Wilson / Daniel G. Foster / Benjamin L. Edelman / Luis A. Ortiz / David A. Schwartz / David W.H. Riches / Elizabeth F. Redente

JCI Insight, Vol 8, Iss

2023 Volume 3

Abstract: Patients with progressive fibrosing interstitial lung diseases (PF-ILDs) carry a poor prognosis and have limited therapeutic options. A hallmark feature is fibroblast resistance to apoptosis, leading to their persistence, accumulation, and excessive ... ...

Abstract	Patients with progressive fibrosing interstitial lung diseases (PF-ILDs) carry a poor prognosis and have limited therapeutic options. A hallmark feature is fibroblast resistance to apoptosis, leading to their persistence, accumulation, and excessive deposition of extracellular matrix. A complex balance of the B cell lymphoma 2 (BCL-2) protein family controlling the intrinsic pathway of apoptosis and fibroblast reliance on antiapoptotic proteins has been hypothesized to contribute to this resistant phenotype. Examination of lung tissue from patients with PF-ILD (idiopathic pulmonary fibrosis and silicosis) and mice with PF-ILD (repetitive bleomycin and silicosis) showed increased expression of antiapoptotic BCL-2 family members in α–smooth muscle actin–positive fibroblasts, suggesting that fibroblasts from fibrotic lungs may exhibit increased susceptibility to inhibition of antiapoptotic BCL-2 family members BCL-2, BCL-XL, and BCL-W with the BH3 mimetic ABT-263. We used 2 murine models of PF-ILD to test the efficacy of ABT-263 in reversing established persistent pulmonary fibrosis. Treatment with ABT-263 induced fibroblast apoptosis, decreased fibroblast numbers, and reduced lung collagen levels, radiographic disease, and histologically evident fibrosis. Our studies provide insight into how fibroblasts gain resistance to apoptosis and become sensitive to the therapeutic inhibition of antiapoptotic proteins. By targeting profibrotic fibroblasts, ABT-263 offers a promising therapeutic option for PF-ILDs.
Keywords	Cell biology ; Pulmonology ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment

Amarpreet Kaur / Susan K. Mathai / David A. Schwartz

Frontiers in Medicine, Vol

2017 Volume 4

Abstract: Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The prognosis of IPF is poor with a median survival of 3–5 years after diagnosis and no curative medical therapies. Although the pathogenesis of IPF is not well understood, there is a growing body of evidence that genetic factors contribute to disease risk. Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants. The IPF-associated genetic loci discovered to date are implicated in diverse biological processes, including alveolar stability, host defense, cell–cell barrier function, and cell senescence. In addition, some common variants have also been associated with distinct clinical phenotypes. Better understanding of how genetic variation plays a role in disease risk and phenotype could identify potential therapeutic targets and inform clinical decision-making. In addition, clinical studies should be designed controlling for the genetic backgrounds of subjects, since clinical outcomes and therapeutic responses may differ by genotype. Further understanding of these differences will allow the development of personalized approaches to the IPF management.
Keywords	idiopathic pulmonary fibrosis ; MUC5B ; pulmonary fibrosis ; interstitial lung disease ; telomeres ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19

Denise Morotti / Massimiliano Cadamuro / Elena Rigoli / Aurelio Sonzogni / Andrea Gianatti / Cristina Parolin / Luisa Patanè / David A. Schwartz

Pathogens, Vol 10, Iss 479, p

2021 Volume 479

Abstract: A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include ...

Abstract	A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.
Keywords	Hofbauer cell ; SARS-CoV-2 ; placenta ; COVID-19 ; fetal infection ; coronavirus ; Medicine ; R
Subject code	570
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The PRECiSE 2 trial of certolizumab pegol, a new PEGylated anti-TNF agent, in the treatment of Crohn's disease - An interview with David A Schwartz, 13 June 2007

David A Schwartz

Biologics: Targets & Therapy, Vol 2008, Iss Issue 1, Pp 125-

2008 Volume 128

Abstract: David A SchwartzVanderbilt University Medical Center, Nashville, TN, USAContext: Certolizumab pegol (CDP 870) is a new anti-tumor necrosis factor (TNF) therapy currently in development for the treatment of Crohn’s disease, rheumatoid arthritis, and ... ...

Abstract	David A SchwartzVanderbilt University Medical Center, Nashville, TN, USAContext: Certolizumab pegol (CDP 870) is a new anti-tumor necrosis factor (TNF) therapy currently in development for the treatment of Crohn’s disease, rheumatoid arthritis, and psoriasis. Certolizumab pegol is the first PEGylated biologic anti-TNF agent and has a high binding affinity for TNF. Dr. Schwartz was an investigator of the PRECiSE (PEGylated Antibody Fragment Evaluation in Crohn’s Disease Safety and Efficacy) 2 trial of certolizumab pegol in patients with Crohn’s disease.Keywords: certolizumab pegol, PRECiSE 2 trial, Crohn’s disease
Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2008-03-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional

Ian T. Stancil / Jacob E. Michalski / Duncan Davis-Hall / Hong Wei Chu / Jin-Ah Park / Chelsea M. Magin / Ivana V. Yang / Bradford J. Smith / Evgenia Dobrinskikh / David A. Schwartz

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 11

Abstract: Environmental and genetic risk factors affect the distal airway epithelium in idiopatic pulmonary fibrosis (IPF) but the role of the epithelium in IPF remains unclear. Here the authors show that pathologic activation of the ERBB-YAP axis induces dynamic ... ...

Abstract	Environmental and genetic risk factors affect the distal airway epithelium in idiopatic pulmonary fibrosis (IPF) but the role of the epithelium in IPF remains unclear. Here the authors show that pathologic activation of the ERBB-YAP axis induces dynamic and structural dysfunction in the distal airway epithelium eliciting a pro-fibrotic phenotype in mesenchymal cells.
Keywords	Science ; Q
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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