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Article ; Online: SARS-CoV-2: Combating Coronavirus Emergence.

Graham, Rachel L / Baric, Ralph S

2020 Volume 52, Issue 5, Page(s) 734–736

Abstract: The emergence and rapid global spread of SARS-CoV-2 mark the third such identification of a novel coronavirus capable of causing severe, potentially fatal disease in humans in the ... ...

Abstract	The emergence and rapid global spread of SARS-CoV-2 mark the third such identification of a novel coronavirus capable of causing severe, potentially fatal disease in humans in the 21
MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS Virus ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-05-08
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.04.016
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Article ; Online: Assessment of Kentucky's Local Health Department Cross-Jurisdictional Sharing: Strategy for Maximizing Efficiency.

Carman, Angela L / Gatton, Kelsey / Hogg-Graham, Rachel

Journal of public health management and practice : JPHMP

2022 Volume 28, Issue 6, Page(s) E808–E814

Abstract: Objective: The purpose of this study was to examine patterns of cross-jurisdictional sharing across the 61 local public health jurisdictions (LHJs) in Kentucky. The opportunities to reduce the cost-of-service delivery for Kentucky's LHJs via cross- ... ...

Abstract	Objective: The purpose of this study was to examine patterns of cross-jurisdictional sharing across the 61 local public health jurisdictions (LHJs) in Kentucky. The opportunities to reduce the cost-of-service delivery for Kentucky's LHJs via cross-jurisdictional sharing present a mechanism to address financial instability across the state by achieving economies of scale, especially among smaller jurisdictions. Design: A cross-sectional study design was used to examine patterns of cross-jurisdictional sharing across the 61 LHJs in Kentucky. The survey tool utilized was designed by the Center for Sharing Public Health Services, an initiative managed by the Kansas Health Institute with support from the Robert Wood Johnson Foundation. Results: Seventy-two percent of the 61 LHJs in Kentucky responded to the survey. The majority of responding jurisdictions sharing services were rural, single-county jurisdictions, utilizing service-related informal sharing arrangements. The majority of health departments, when asked to identify which programmatic areas shared service arrangements were focused in, listed those services requiring intensive staff training such as Health Access Nurturing Development Services (HANDS) and epidemiology. Of particular interest were the services most infrequently shared such as communicable disease screening and treatment. Conclusions: This study suggests that, pre-COVID-19, a core group of primarily rural, single-county Kentucky local health departments has experience with cross-jurisdictional sharing. Among this group, engagement in informal arrangements was the form of cross-jurisdictional sharing predominantly used, with few jurisdictions reporting shared functions with joint oversight. When considering the potential benefits and efficiencies that cross-jurisdictional sharing can provide to public health departments and their communities, for some, COVID-19 may have been a catalyst to engage in sharing across health department jurisdictional lines.
MeSH term(s)	COVID-19/epidemiology ; Cross-Sectional Studies ; Humans ; Kentucky ; Mass Screening ; Public Health
Language	English
Publishing date	2022-08-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2027860-3
ISSN	1550-5022 ; 1078-4659
ISSN (online)	1550-5022
ISSN	1078-4659
DOI	10.1097/PHH.0000000000001594
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Article ; Online: Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

Ananth, Cande V / Lee, Rachel / Valeri, Linda / Ross, Zev / Graham, Hillary L / Khan, Shama P / Cabrera, Javier / Rosen, Todd / Kostis, William J

Paediatric and perinatal epidemiology

2024 Volume 38, Issue 3, Page(s) 271–286

Abstract: Background: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for ... ...

Abstract	Background: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. Objectives: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. Population: All subjects who delivered in New Jersey, USA, between 1993 and 2020. Design: Retrospective, population-based, birth cohort study. Methods: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. Preliminary results: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. Conclusions: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.
MeSH term(s)	Pregnancy ; Female ; Infant, Newborn ; Humans ; Abruptio Placentae/epidemiology ; Cohort Studies ; Retrospective Studies ; Placenta ; Risk Factors ; Pregnancy Complications, Cardiovascular/epidemiology ; Fetal Death ; Chronic Disease
Language	English
Publishing date	2024-01-26
Publishing country	England
Document type	Journal Article
ZDB-ID	639089-4
ISSN	1365-3016 ; 0269-5022 ; 1353-663X
ISSN (online)	1365-3016
ISSN	0269-5022 ; 1353-663X
DOI	10.1111/ppe.13039
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Article ; Online: Joint developmental trajectories of internalizing and externalizing problems from mid-childhood to late adolescence and childhood risk factors: Findings from a prospective pre-birth cohort.

Bista, Sarita / Tait, Robert J / Straker, Leon M / Lin, Ashleigh / Steinbeck, Katharine / Graham, Petra L / Kang, Melissa / Lymer, Sharyn / Robinson, Monique / Marino, Jennifer L / Skinner, S Rachel

Development and psychopathology

2024 , Page(s) 1–16

Abstract: There is limited evidence on heterogenous co-developmental trajectories of internalizing (INT) and externalizing (EXT) problems from childhood to adolescence and predictors of these joint trajectories. We utilized longitudinal data from Raine Study ... ...

Abstract	There is limited evidence on heterogenous co-developmental trajectories of internalizing (INT) and externalizing (EXT) problems from childhood to adolescence and predictors of these joint trajectories. We utilized longitudinal data from Raine Study participants (
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	1036173-x
ISSN	1469-2198 ; 0954-5794
ISSN (online)	1469-2198
ISSN	0954-5794
DOI	10.1017/S0954579423001505
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Article ; Online: SARS-CoV-2

Graham, Rachel L. / Baric, Ralph S.

Immunity

Combating Coronavirus Emergence

2020 Volume 52, Issue 5, Page(s) 734–736

Keywords	Immunology ; Immunology and Allergy ; Infectious Diseases ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.04.016
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Food Allergen Immunotherapy in Preschool Children: Do We Have the Evidence?

Loke, Paxton / Vickery, Brian P / Jones, Stacie M / Peters, Rachel L / Roberts, Graham / Koplin, Jennifer J

The journal of allergy and clinical immunology. In practice

2023 Volume 11, Issue 4, Page(s) 1028–1035

Abstract: Standard care for the management of food allergies previously centered on allergen avoidance and the treatment of adverse reactions after allergen exposure. An increase in the development of immunotherapy treatments for food allergy has occurred over the ...

Abstract	Standard care for the management of food allergies previously centered on allergen avoidance and the treatment of adverse reactions after allergen exposure. An increase in the development of immunotherapy treatments for food allergy has occurred over the past 2 decades, with many centers now offering immunotherapy. Previous studies mainly focused on school-age children in whom food allergies are likely to be persistent. However, there is increasing evidence that delivering immunotherapy for food allergy to preschool-age children may deliver higher rates of success, and that peanut allergen immunotherapy leads the way. Conversely, the natural resolution of food allergies occurs primarily in these younger age groups, resulting in challenges to selecting patients who will ultimately benefit from these treatments. Both immunotherapy and natural history studies reveal the inherent plasticity of the immune system in early life, which may be more amenable to intervention, but this raises a delicate yet unknown balance between the optimal timing of intervention versus waiting for natural resolution of the food allergy. Here we review the evidence for early food allergen immunotherapy in preschoolers, and present the pros and cons of this approach while acknowledging important research gaps in this age group.
MeSH term(s)	Child, Preschool ; Humans ; Food Hypersensitivity/therapy ; Food Hypersensitivity/etiology ; Desensitization, Immunologic/methods ; Immunotherapy ; Allergens ; Arachis ; Administration, Oral
Chemical Substances	Allergens
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2023.01.005
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Article: SARS-CoV-2: Combating Coronavirus Emergence

Graham, Rachel L / Baric, Ralph S

Immunity

Abstract: The emergence and rapid global spread of SARS-CoV-2 mark the third such identification of a novel coronavirus capable of causing severe, potentially fatal disease in humans in the 21st century. As noted by Andersen et al. (Nature Medicine), the ... ...

Abstract	The emergence and rapid global spread of SARS-CoV-2 mark the third such identification of a novel coronavirus capable of causing severe, potentially fatal disease in humans in the 21st century. As noted by Andersen et al. (Nature Medicine), the sequencing of proximal zoonotic ancestors to SARS-CoV-2 has aided in the identification of alleles that may contribute to the virus' virulence in humans.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #125392
Database	COVID19

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Article ; Online: SARS-CoV-2

Graham, Rachel L. / Baric, Ralph S.

Immunity, 52(5)

Combating Coronavirus Emergence

2020

Abstract: The emergence and rapid global spread of SARS-CoV-2 mark the third such identiﬁcation of a novel corona- virus capable of causing severe, potentially fatal disease in humans in the 21st century. As noted by Andersen et al. (Nature Medicine), the ... ...

Abstract	The emergence and rapid global spread of SARS-CoV-2 mark the third such identiﬁcation of a novel corona- virus capable of causing severe, potentially fatal disease in humans in the 21st century. As noted by Andersen et al. (Nature Medicine), the sequencing of proximal zoonotic ancestors to SARS-CoV-2 has aided in the iden- tiﬁcation of alleles that may contribute to the virus’ virulence in humans.
Keywords	covid19
Language	English
Publishing country	us
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19.

Boon, Adrianus C M / L Bricker, Traci / Fritch, Ethan J / Leist, Sarah R / Gully, Kendra / Baric, Ralph S / Graham, Rachel L / Troan, Brigid V / Mahoney, Matthew / Janetka, James W

bioRxiv : the preprint server for biology

2024

Abstract: We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including transmembrane protease serine 2 (TMPRSS2), matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly ... ...

Abstract	We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including transmembrane protease serine 2 (TMPRSS2), matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have previously shown that compound MM3122 exhibited sub nanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell-viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Further, we have evaluated MM3122 in a mouse model of COVID-19 and have demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion, and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in pro-inflammatory cytokines and chemokines production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2 infected mice. Therefore, MM3122 is a promising lead candidate small molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses. Importance: SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host-cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and therapeutic drug for the treatment of COVID-19 in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.
Language	English
Publishing date	2024-02-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.09.579701
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Article ; Online: Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19.

Boon, Adrianus C M / Bricker, Traci L / Fritch, Ethan J / Leist, Sarah R / Gully, Kendra / Baric, Ralph S / Graham, Rachel L / Troan, Brigid V / Mahoney, Matthew / Janetka, James W

Journal of virology

2024 , Page(s) e0190323

Abstract: We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in ...

Abstract	We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Furthermore, we evaluated MM3122 in a mouse model of COVID-19 and demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in proinflammatory cytokine and chemokine production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2-infected mice. Therefore, MM3122 is a promising lead candidate small-molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses. Importance: SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and a therapeutic drug for the treatment of COVID-19 given intraperitoneally in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research, but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01903-23
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