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  1. Article ; Online: In the Age of COVID: Genomic Changes Over the Lifespan Help Explain Severe SARS-CoV-2 Disease.

    Beddingfield, Brandon J / Bix, Gregory J

    JACC. Basic to translational science

    2020  Volume 5, Issue 11, Page(s) 1124–1126

    Keywords covid19
    Language English
    Publishing date 2020-10-23
    Publishing country United States
    Document type Editorial ; Comment
    ISSN 2452-302X
    ISSN (online) 2452-302X
    DOI 10.1016/j.jacbts.2020.10.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Real-Time Analysis of SARS-CoV-2-Induced Cytolysis Reveals Distinct Variant-Specific Replication Profiles.

    Scheuermann, Sarah E / Goff, Kelly / Rowe, Lori A / Beddingfield, Brandon J / Maness, Nicholas J

    Viruses

    2023  Volume 15, Issue 9

    Abstract: The ability of each new SARS-CoV-2 variant to evade host humoral immunity is the focus of intense research. Each variant may also harbor unique replication capabilities relevant for disease and transmission. Here, we demonstrate a new approach to ... ...

    Abstract The ability of each new SARS-CoV-2 variant to evade host humoral immunity is the focus of intense research. Each variant may also harbor unique replication capabilities relevant for disease and transmission. Here, we demonstrate a new approach to assessing viral replication kinetics using real-time cell analysis (RTCA). Virus-induced cell death is measured in real time as changes in electrical impedance through cell monolayers while images are acquired at defined intervals via an onboard microscope and camera. Using this system, we quantified replication kinetics of five clinically important viral variants: WA1/2020 (ancestral), Delta, and Omicron subvariants BA.1, BA.4, and BA.5. Multiple measures proved useful in variant replication comparisons, including the elapsed time to, and the slope at, the maximum rate of cell death. Important findings include significantly weaker replication kinetics of BA.1 by all measures, while BA.5 harbored replication kinetics at or near ancestral levels, suggesting evolution to regain replicative capacity, and both an altered profile of cell killing and enhanced fusogenicity of the Delta variant. Together, these data show that RTCA is a robust method to assess replicative capacity of any given SARS-CoV-2 variant rapidly and quantitatively, which may be useful in assessment of newly emerging variants.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Cell Death ; Apoptosis
    Language English
    Publishing date 2023-09-16
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15091937
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: In the Age of CoVID

    Beddingfield, Brandon J. / Bix, Gregory J.

    JACC: Basic to Translational Science ; ISSN 2452-302X

    Genomic Changes Over the Lifespan Help Explain Severe SARS-CoV-2 Disease

    2020  

    Keywords Cardiology and Cardiovascular Medicine ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    DOI 10.1016/j.jacbts.2020.10.004
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques.

    Beddingfield, Brandon J / Plante, Kenneth S / Plante, Jessica A / Weaver, Scott C / Bose, Sarah / Krzykwa, Clara / Chirichella, Nicole / Redmann, Rachel K / Seiler, Stephanie Z / Dufour, Jason / Blair, Robert V / Endt, Kathrin / Volkmann, Ariane / Maness, Nicholas J / Roy, Chad J

    NPJ vaccines

    2024  Volume 9, Issue 1, Page(s) 47

    Abstract: MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques ... ...

    Abstract MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 10
    Language English
    Publishing date 2024-02-27
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-024-00842-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Real time analysis of SARS-CoV-2 induced cytolysis reveals distinct variant-specific replication profiles

    Scheuermann, Sarah E / Goff, Kelly A / Rowe, Lori A / Beddingfield, Brandon J / Maness, Nicholas J

    bioRxiv

    Abstract: The continuous evolution of new SARS-CoV-2 variants with enhanced immune evasion capacity suggests the entire population is and will continue to be potentially vulnerable to infection despite pre-existing immunity. The ability of each new variant to ... ...

    Abstract The continuous evolution of new SARS-CoV-2 variants with enhanced immune evasion capacity suggests the entire population is and will continue to be potentially vulnerable to infection despite pre-existing immunity. The ability of each new variant to evade host humoral immunity is the focus of intense research across the globe. Each variant may also harbor unique replication capabilities relevant for disease and transmission. Here we demonstrate the utility of a new approach to assessing viral replication kinetics using Real Time Cell Analysis (RTCA). Virus induced cell death is measured in real time by the detection of electrical impedance through cell monolayers. Using this system, we quantified replication kinetics of five clinically important viral variants; USA WA1/2020 (an A1 ancestral lineage isolate), Delta, and Omicron subvariants BA.1, BA.4, and BA.5. We identified multiple kinetic measures that proved useful in variant replication comparisons including time (in hours) to the maximum rate of cell death at each log10 viral dilution and the slope at the maximum rate of cell death. We found that WA1/2020 and Delta were the most rapid but in distinct ways. While WA1/2020 induced cell death most rapidly after inoculation, Delta was slightly slower to reach cell death, it appeared to kill cells faster once cytotoxic effects began. Interestingly, BA.1, showed substantially reduced replication kinetics relative to all other variants. Together, these data show that real time analysis of cell death is a robust method to assess replicative capacity of any given SARS-CoV-2 variant rapidly and quantitatively, which may be useful in assessment of newly emerging variants.
    Keywords covid19
    Language English
    Publishing date 2023-03-28
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.03.28.534588
    Database COVID19

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  7. Article ; Online: Intra-Host SARS-CoV-2 Evolution in the Gut of Mucosally-Infected

    Rowe, Lori A / Beddingfield, Brandon J / Goff, Kelly / Killeen, Stephanie Z / Chirichella, Nicole R / Melton, Alexandra / Roy, Chad J / Maness, Nicholas J

    Viruses

    2022  Volume 14, Issue 1

    Abstract: In recent months, several SARS-CoV-2 variants have emerged that enhance transmissibility and escape host humoral immunity. Hence, the tracking of viral evolutionary trajectories is clearly of great importance. Little is known about SARS-CoV-2 evolution ... ...

    Abstract In recent months, several SARS-CoV-2 variants have emerged that enhance transmissibility and escape host humoral immunity. Hence, the tracking of viral evolutionary trajectories is clearly of great importance. Little is known about SARS-CoV-2 evolution in nonhuman primate models used to test vaccines and therapies and to model human disease. Viral RNA was sequenced from rectal swabs from
    MeSH term(s) Animals ; COVID-19/virology ; Chlorocebus aethiops ; Disease Models, Animal ; Evolution, Molecular ; Mutation ; Polyproteins/genetics ; RNA, Viral/genetics ; Rectum/virology ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Vero Cells ; Viral Proteins/genetics
    Chemical Substances ORF1ab polyprotein, SARS-CoV-2 ; Polyproteins ; RNA, Viral ; Spike Glycoprotein, Coronavirus ; Viral Proteins ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-01-01
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14010077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Phenotypic and Kinetic Changes of Myeloid Lineage Cells in Innate Response to Chikungunya Infection in Cynomolgus Macaques.

    Beddingfield, Brandon J / Sugimoto, Chie / Wang, Eryu / Weaver, Scott C / Russell-Lodrigue, Kasi E / Killeen, Stephanie Z / Kuroda, Marcelo J / Roy, Chad J

    Viral immunology

    2022  Volume 35, Issue 3, Page(s) 192–199

    Abstract: Chikungunya (CHIKV) is an emerging worldwide viral threat. The immune response to infection can lead to protection and convalescence or result in long-term sequelae such as arthritis. Early innate immune events during acute infection have been ... ...

    Abstract Chikungunya (CHIKV) is an emerging worldwide viral threat. The immune response to infection can lead to protection and convalescence or result in long-term sequelae such as arthritis. Early innate immune events during acute infection have been characterized for some cell types, but more must be elucidated with respect to cellular responses of monocytes and other myeloid lineage cells. In addition to their roles in protection and inflammation resolution, monocytes and macrophages are sites for viral replication and may also act as viral reservoirs. These cells are also found in joints postinfection, possibly playing a role in long-term CHIKV-induced pathology. We examined kinetic and phenotypic changes in myeloid lineage cells, including monocytes, in cynomolgus macaques early after experimental infection with CHIKV. We found increased proliferation of monocytes and decreased proliferation of myeloid dendritic cells early during infection, with an accompanying decrease in absolute numbers of both cell types, as well as a simultaneous increase in plasmacytoid dendritic cell number. An increase in CD16 and CD14 was seen along with a decrease in monocyte Human Leukocyte Antigen-DR isotype expression within 3 days of infection, potentially indicating monocyte deactivation. A transient decrease in T cells, B cells, and natural killer cells correlated with lymphocytopenia observed during human infections with CHIKV. CD4
    MeSH term(s) Animals ; Cell Lineage ; Chikungunya Fever/complications ; Kinetics ; Macaca ; Monocytes
    Language English
    Publishing date 2022-03-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639075-4
    ISSN 1557-8976 ; 0882-8245
    ISSN (online) 1557-8976
    ISSN 0882-8245
    DOI 10.1089/vim.2021.0171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A Miniaturized Electrostatic Precipitator Respirator Effectively Removes Ambient SARS-CoV-2 Bioaerosols.

    Redmann, Rachel K / Beddingfield, Brandon J / Spencer, Skye / Chirichella, Nicole R / Henley, Julian L / Hager, Wes / Roy, Chad J

    Viruses

    2022  Volume 14, Issue 4

    Abstract: The inhalation of ambient SARS-CoV-2-containing bioaerosols leads to infection and pandemic airborne transmission in susceptible populations. Filter-based respirators effectively reduce exposure but complicate normal respiration through breathing zone ... ...

    Abstract The inhalation of ambient SARS-CoV-2-containing bioaerosols leads to infection and pandemic airborne transmission in susceptible populations. Filter-based respirators effectively reduce exposure but complicate normal respiration through breathing zone pressure differentials; therefore, they are impractical for long-term use.
    Objectives: We tested the comparative effectiveness of a prototyped miniaturized electrostatic precipitator (mEP) on a filter-based respirator (N95) via the removal of viral bioaerosols from a simulated, inspired air stream.
    Measurements and main results: The mEP respirator removed particles (96.5 ± 0.4%), approximating efficiencies of the N95 (96.9 ± 0.6%). The mEP respirator similarly decreased SARS-CoV-2 viral RNA (99.792%) when compared to N95 removal (99.942%), as a function of particle removal from the airstream distal to the breathing zone of each respirator.
    Conclusions: The mEP respirator approximated the performance of a filter-based N95 respirator for particle removal and viral RNA as a constituent of the SARS-CoV-2 bioaerosols generated for this evaluation. In practice, the mEP respirator could provide equivalent protection from ambient infectious bioaerosols as the N95 respirator without undue pressure drop to the wearer, thereby facilitating its long-term use in an unobstructed breathing configuration.
    MeSH term(s) COVID-19/prevention & control ; Humans ; RNA, Viral ; SARS-CoV-2 ; Static Electricity ; Ventilators, Mechanical
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2022-04-06
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14040765
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Mid-titer human convalescent plasma administration results in suboptimal prophylaxis against SARS-CoV-2 infection in rhesus macaques.

    Beddingfield, Brandon J / Maness, Nicholas J / Spencer, Skye / Rappaport, Jay / Aye, Pyone Pyone / Russell-Lodrigue, Kasi / Doyle-Meyers, Lara A / Blair, Robert V / Gao, HongMei / Montefiori, David / Roy, Chad J

    Frontiers in immunology

    2023  Volume 14, Page(s) 1085883

    Abstract: Introduction: ARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to ... ...

    Abstract Introduction: ARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate the added benefit of prophylactic administration of human post-SARS-CoV-2 infection convalescent plasma (CP) on disease progression and severity.
    Methods: A pharmacokinetic (PK) study using CP in rhesus monkeys preceded the challenge study and revealed the optimal time of tissue distribution for maximal effect. Thereafter, CP was administered prophylactically three days prior to mucosal SARS-CoV-2 viral challenge.
    Results: Results show similar viral kinetics in mucosal sites over the course of infection independent of administration of CP or normal plasma, or historic controls with no plasma. No changes were noted upon necropsy via histopathology, although there were differences in levels of vRNA in tissues, with both normal and CP seemingly blunting viral loads.
    Discussion: Results indicate that prophylactic administration with mid-titer CP is not effective in reducing disease severity of SARS-CoV-2 infection in the rhesus COVID-19 disease model.
    MeSH term(s) Animals ; Humans ; COVID-19 ; Macaca mulatta ; SARS-CoV-2 ; Immunization, Passive/methods ; COVID-19 Serotherapy
    Language English
    Publishing date 2023-02-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1085883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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