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Article ; Online: Coagulation and wound repair during COVID-19.

Menachery, Vineet D / Gralinski, Lisa E

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

2021 Volume 40, Issue 10, Page(s) 1076–1081

Abstract: While COVID-19 is best known as a respiratory infection, SARS-CoV-2 causes systemic disease manifestations including coagulopathies. Both dysregulated extracellular matrix remodeling pathways and circulating coagulation proteins are hallmarks of severe ... ...

Abstract	While COVID-19 is best known as a respiratory infection, SARS-CoV-2 causes systemic disease manifestations including coagulopathies. Both dysregulated extracellular matrix remodeling pathways and circulating coagulation proteins are hallmarks of severe COVID-19 and often continue after the resolution of acute infection. Coagulation proteins have proven effective as biomarkers for severe disease and anticoagulants are a mainstay of COVID-19 therapeutics in hospitalized patients. While much knowledge has been gained about the role of clotting pathway activation in COVID-19, much remains to be elucidated in this complex network of signaling pathways.
MeSH term(s)	Blood Coagulation Disorders/etiology ; COVID-19/complications ; COVID-19/physiopathology ; Humans ; Wound Healing
Language	English
Publishing date	2021-06-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1062522-7
ISSN	1557-3117 ; 1053-2498
ISSN (online)	1557-3117
ISSN	1053-2498
DOI	10.1016/j.healun.2021.06.006
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Article ; Online: Return of the Coronavirus: 2019-nCoV.

Gralinski, Lisa E / Menachery, Vineet D

Viruses

2020 Volume 12, Issue 2

Abstract: The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the ...

Abstract	The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.
MeSH term(s)	Animals ; Betacoronavirus/genetics ; Betacoronavirus/isolation & purification ; COVID-19 ; China ; Communicable Diseases, Emerging ; Coronavirus Infections/epidemiology ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Disease Outbreaks ; Disease Reservoirs ; Disease Susceptibility ; Genome, Viral ; Humans ; Nucleocapsid Proteins/chemistry ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/transmission ; Pneumonia, Viral/virology ; SARS Virus/chemistry ; SARS Virus/genetics ; SARS-CoV-2 ; Severe Acute Respiratory Syndrome/epidemiology ; Severe Acute Respiratory Syndrome/virology ; Social Media ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism ; Zoonoses
Chemical Substances	Nucleocapsid Proteins ; Spike Glycoprotein, Coronavirus
Keywords	covid19
Language	English
Publishing date	2020-01-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12020135
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Article: Return of the Coronavirus: 2019-nCoV

Gralinski, Lisa E / Menachery, Vineet D

Viruses

Abstract	The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #61
Database	COVID19

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Article ; Online: Return of the Coronavirus

Gralinski, Lisa E. / Menachery, Vineet

Viruses, 12(2):135

2019-nCoV

2020

Abstract	The emergence of a novel coronavirus (2019-nCoV) has awakened the echoes of SARS-CoV from nearly two decades ago. Yet, with technological advances and important lessons gained from previous outbreaks, perhaps the world is better equipped to deal with the most recent emergent group 2B coronavirus.
Keywords	COVID-19 ; SARS-CoV ; Wuhan ; MERS-CoV ; emerging viruses ; 2019-nCoV ; novel CoV ; Coronavirus ; Wuhan pneumonia ; covid19
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular pathology of emerging coronavirus infections.

Gralinski, Lisa E / Baric, Ralph S

The Journal of pathology

2015 Volume 235, Issue 2, Page(s) 185–195

Abstract: Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute ... ...

Abstract	Respiratory viruses can cause a wide spectrum of pulmonary diseases, ranging from mild, upper respiratory tract infections to severe and life-threatening lower respiratory tract infections, including the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Viral clearance and subsequent recovery from infection require activation of an effective host immune response; however, many immune effector cells may also cause injury to host tissues. Severe acute respiratory syndrome (SARS) coronavirus and Middle East respiratory syndrome (MERS) coronavirus cause severe infection of the lower respiratory tract, with 10% and 35% overall mortality rates, respectively; however, >50% mortality rates are seen in the aged and immunosuppressed populations. While these viruses are susceptible to interferon treatment in vitro, they both encode numerous genes that allow for successful evasion of the host immune system until after high virus titres have been achieved. In this review, we discuss the importance of the innate immune response and the development of lung pathology following human coronavirus infection.
MeSH term(s)	Animals ; Antiviral Agents/therapeutic use ; Biopsy ; Communicable Diseases, Emerging ; Coronavirus/drug effects ; Coronavirus/immunology ; Coronavirus/isolation & purification ; Coronavirus/pathogenicity ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/pathology ; Coronavirus Infections/virology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Middle East Respiratory Syndrome Coronavirus/isolation & purification ; Middle East Respiratory Syndrome Coronavirus/pathogenicity ; Pathology, Molecular/methods ; Predictive Value of Tests ; Respiratory System/drug effects ; Respiratory System/immunology ; Respiratory System/pathology ; Respiratory System/virology ; Risk Factors ; Severe acute respiratory syndrome-related coronavirus/isolation & purification ; Severe acute respiratory syndrome-related coronavirus/pathogenicity ; Severe Acute Respiratory Syndrome/drug therapy ; Severe Acute Respiratory Syndrome/pathology ; Severe Acute Respiratory Syndrome/virology ; Virology/methods ; Virulence
Chemical Substances	Antiviral Agents
Keywords	covid19
Language	English
Publishing date	2015-05-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.4454
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Article ; Online: Genetic loci regulate Sarbecovirus pathogenesis: A comparison across mice and humans.

Schäfer, Alexandra / Gralinski, Lisa E / Leist, Sarah R / Hampton, Brea K / Mooney, Michael A / Jensen, Kara L / Graham, Rachel L / Agnihothram, Sudhakar / Jeng, Sophia / Chamberlin, Steven / Bell, Timothy A / Scobey, D Trevor / Linnertz, Colton L / VanBlargan, Laura A / Thackray, Larissa B / Hock, Pablo / Miller, Darla R / Shaw, Ginger D / Diamond, Michael S /

de Villena, Fernando Pardo Manuel / McWeeney, Shannon K / Heise, Mark T / Menachery, Vineet D / Ferris, Martin T / Baric, Ralph S

Virus research

2024 Volume 344, Page(s) 199357

Abstract: Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although ... ...

Abstract	Coronavirus (CoV) cause considerable morbidity and mortality in humans and other mammals, as evidenced by the emergence of Severe Acute Respiratory CoV (SARS-CoV) in 2003, Middle East Respiratory CoV (MERS-CoV) in 2012, and SARS-CoV-2 in 2019. Although poorly characterized, natural genetic variation in human and other mammals modulate virus pathogenesis, as reflected by the spectrum of clinical outcomes ranging from asymptomatic infections to lethal disease. Using multiple human epidemic and zoonotic Sarbecoviruses, coupled with murine Collaborative Cross genetic reference populations, we identify several dozen quantitative trait loci that regulate SARS-like group-2B CoV pathogenesis and replication. Under a Chr4 QTL, we deleted a candidate interferon stimulated gene, Trim14 which resulted in enhanced SARS-CoV titers and clinical disease, suggesting an antiviral role during infection. Importantly, about 60 % of the murine QTL encode susceptibility genes identified as priority candidates from human genome-wide association studies (GWAS) studies after SARS-CoV-2 infection, suggesting that similar selective forces have targeted analogous genes and pathways to regulate Sarbecovirus disease across diverse mammalian hosts. These studies provide an experimental platform in rodents to investigate the molecular-genetic mechanisms by which potential cross mammalian susceptibility loci and genes regulate type-specific and cross-SARS-like group 2B CoV replication, immunity, and pathogenesis in rodent models. Our study also provides a paradigm for identifying susceptibility loci for other highly heterogeneous and virulent viruses that sporadically emerge from zoonotic reservoirs to plague human and animal populations.
MeSH term(s)	Animals ; Humans ; Mice ; Quantitative Trait Loci ; SARS-CoV-2/genetics ; Virus Replication ; Genome-Wide Association Study ; COVID-19/virology ; Tripartite Motif Proteins/genetics ; Coronavirus Infections/virology ; Coronavirus Infections/genetics ; Disease Models, Animal
Chemical Substances	Tripartite Motif Proteins
Language	English
Publishing date	2024-03-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comparative Study
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2024.199357
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Article ; Online: Understanding COVID-19-associated coagulopathy.

Conway, Edward M / Mackman, Nigel / Warren, Ronald Q / Wolberg, Alisa S / Mosnier, Laurent O / Campbell, Robert A / Gralinski, Lisa E / Rondina, Matthew T / van de Veerdonk, Frank L / Hoffmeister, Karin M / Griffin, John H / Nugent, Diane / Moon, Kyung / Morrissey, James H

Nature reviews. Immunology

2022 Volume 22, Issue 10, Page(s) 639–649

Abstract: COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex ... ...

Abstract	COVID-19-associated coagulopathy (CAC) is a life-threatening complication of SARS-CoV-2 infection. However, the underlying cellular and molecular mechanisms driving this condition are unclear. Evidence supports the concept that CAC involves complex interactions between the innate immune response, the coagulation and fibrinolytic pathways, and the vascular endothelium, resulting in a procoagulant condition. Understanding of the pathogenesis of this condition at the genomic, molecular and cellular levels is needed in order to mitigate thrombosis formation in at-risk patients. In this Perspective, we categorize our current understanding of CAC into three main pathological mechanisms: first, vascular endothelial cell dysfunction; second, a hyper-inflammatory immune response; and last, hypercoagulability. Furthermore, we pose key questions and identify research gaps that need to be addressed to better understand CAC, facilitate improved diagnostics and aid in therapeutic development. Finally, we consider the suitability of different animal models to study CAC.
MeSH term(s)	Animals ; Blood Coagulation Disorders/etiology ; COVID-19/complications ; Endothelium, Vascular ; SARS-CoV-2 ; Thrombosis/etiology
Language	English
Publishing date	2022-08-05
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-022-00762-9
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Article ; Online: Protective Efficacy of Rhesus Adenovirus COVID-19 Vaccines against Mouse-Adapted SARS-CoV-2.

Tostanoski, Lisa H / Gralinski, Lisa E / Martinez, David R / Schaefer, Alexandra / Mahrokhian, Shant H / Li, Zhenfeng / Nampanya, Felix / Wan, Huahua / Yu, Jingyou / Chang, Aiquan / Liu, Jinyan / McMahan, Katherine / Ventura, John D / Dinnon, Kenneth H / Leist, Sarah R / Baric, Ralph S / Barouch, Dan H

Journal of virology

2021 Volume 95, Issue 23, Page(s) e0097421

Abstract: The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus ... ...

Abstract	The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice.
MeSH term(s)	Adenoviridae Infections/immunology ; Adenovirus Vaccines/immunology ; Adenoviruses, Simian/immunology ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Disease Models, Animal ; Female ; Humans ; Immunogenicity, Vaccine ; Macaca mulatta/virology ; Mice ; Mice, Inbred BALB C ; Pandemics/prevention & control ; SARS-CoV-2/immunology ; SARS-CoV-2/pathogenicity ; Vaccination
Chemical Substances	Adenovirus Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2021-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00974-21
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Article: Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2.

Tostanoski, Lisa H / Gralinski, Lisa E / Martinez, David R / Schaefer, Alexandra / Mahrokhian, Shant H / Li, Zhenfeng / Nampanya, Felix / Wan, Huahua / Yu, Jingyou / Chang, Aiquan / Liu, Jinyan / McMahan, Katherine / Dinnon, Kenneth H / Leist, Sarah R / Baric, Ralph S / Barouch, Dan H

bioRxiv : the preprint server for biology

2021

Abstract	The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice. Importance: We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibits a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative Ad vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to i) evaluate the protective efficacy of RhAd52 vaccines and ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.
Language	English
Publishing date	2021-06-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.06.14.448461
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Article ; Online: New Metrics for Evaluating Viral Respiratory Pathogenesis.

Menachery, Vineet D / Gralinski, Lisa E / Baric, Ralph S / Ferris, Martin T

PloS one

2015 Volume 10, Issue 6, Page(s) e0131451

Abstract: Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was ... ...

Abstract	Viral pathogenesis studies in mice have relied on markers of severe systemic disease, rather than clinically relevant measures, to evaluate respiratory virus infection; thus confounding connections to human disease. Here, whole-body plethysmography was used to directly measure changes in pulmonary function during two respiratory viral infections. This methodology closely tracked with traditional pathogenesis metrics, distinguished both virus- and dose-specific responses, and identified long-term respiratory changes following both SARS-CoV and Influenza A Virus infection. Together, the work highlights the utility of examining respiratory function following infection in order to fully understand viral pathogenesis.
MeSH term(s)	Animals ; Chlorocebus aethiops ; Disease Models, Animal ; Dogs ; Influenza A Virus, H1N1 Subtype ; Lung/pathology ; Lung/virology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred C57BL ; Orthomyxoviridae Infections/physiopathology ; Plethysmography, Whole Body ; Predictive Value of Tests ; Severe acute respiratory syndrome-related coronavirus ; Severe Acute Respiratory Syndrome/physiopathology ; Vero Cells ; Viral Load ; Virus Replication/physiology
Keywords	covid19
Language	English
Publishing date	2015-06-26
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0131451
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