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  1. Article ; Online: Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

    Hsieh, Ching-Lin / Leist, Sarah R / Miller, Emily Happy / Zhou, Ling / Powers, John M / Tse, Alexandra L / Wang, Albert / West, Ande / Zweigart, Mark R / Schisler, Jonathan C / Jangra, Rohit K / Chandran, Kartik / Baric, Ralph S / McLellan, Jason S

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1553

    Abstract: Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the ...

    Abstract Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.
    MeSH term(s) Female ; Animals ; Humans ; Mice ; SARS-CoV-2 ; COVID-19 Vaccines ; COVID-19/prevention & control ; Antigens, Viral/genetics ; Mice, Inbred BALB C ; Spike Glycoprotein, Coronavirus/genetics ; Antibodies, Neutralizing ; Antibodies, Viral
    Chemical Substances COVID-19 Vaccines ; spike protein, SARS-CoV-2 ; Antigens, Viral ; Spike Glycoprotein, Coronavirus ; Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45404-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Filovirus entry into cells - new insights.

    Miller, Emily Happy / Chandran, Kartik

    Current opinion in virology

    2012  Volume 2, Issue 2, Page(s) 206–214

    Abstract: Filoviruses are hemorrhagic fever-causing agents that produce enveloped virions with a filamentous morphology. The viral surface glycoprotein, GP, orchestrates the surprisingly complex process by which filoviruses gain access to the cytoplasm of their ... ...

    Abstract Filoviruses are hemorrhagic fever-causing agents that produce enveloped virions with a filamentous morphology. The viral surface glycoprotein, GP, orchestrates the surprisingly complex process by which filoviruses gain access to the cytoplasm of their host cells. GP mediates viral attachment to cells through multiple, redundant interactions with cell-surface factors. GP then induces virion internalization by a process that resembles cellular macropinocytosis. Within the endo/lysosomal pathway, GP undergoes a series of structural rearrangements, controlled by interactions with host factors, that prime and activate it to bring about fusion between the viral and cellular lipid bilayers. Membrane fusion delivers the viral nucleocapsid core into the cytoplasm, which is the site of filovirus replication. This review summarizes our understanding of the filovirus entry mechanism, with emphasis on recent findings.
    MeSH term(s) Animals ; Filoviridae/genetics ; Filoviridae/physiology ; Filoviridae Infections/virology ; Humans ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism ; Virus Internalization
    Chemical Substances Viral Envelope Proteins
    Keywords covid19
    Language English
    Publishing date 2012-03-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2012.02.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Pretest Symptom Duration and Cycle Threshold Values for Severe Acute Respiratory Syndrome Coronavirus 2 Reverse-Transcription Polymerase Chain Reaction Predict Coronavirus Disease 2019 Mortality.

    Miller, Emily Happy / Zucker, Jason / Castor, Delivette / Annavajhala, Medini K / Sepulveda, Jorge L / Green, Daniel A / Whittier, Susan / Scherer, Matthew / Medrano, Nicola / Sobieszczyk, Magdalena E / Yin, Michael T / Kuhn, Louise / Uhlemann, Anne-Catrin

    Open forum infectious diseases

    2021  Volume 8, Issue 2, Page(s) ofab003

    Abstract: Background: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. ... ...

    Abstract Background: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and patient symptom duration in both in- and outpatients, and the impact of these factors on patient outcomes, are currently unknown. Understanding these associations is important to clinicians caring for patients with coronavirus disease 2019 (COVID-19).
    Methods: We conducted an observational study between March 10 and May 30, 2020 at a large quaternary academic medical center in New York City. Patient characteristics, laboratory values, and clinical outcomes were abstracted from the electronic medical records. Of all patients tested for SARS-CoV-2 during this time (N = 16 384), there were 5467 patients with positive tests, 4254 of which had available cycle threshold (Ct) values and were included in further analysis. Univariable and multivariable logistic regression models were used to test associations between Ct values, duration of symptoms before testing, patient characteristics, and mortality. The primary outcome is defined as death or discharge to hospice.
    Results: Lower Ct values at diagnosis (ie, higher viral load) were associated with significantly higher mortality among both in- and outpatients. It is interesting to note that patients with a shorter time since the onset of symptoms to testing had a worse prognosis, with those presenting less than 3 days from symptom onset having 2-fold increased odds of death. After adjusting for time since symptom onset and other clinical covariates, Ct values remained a strong predictor of mortality.
    Conclusions: Severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction Ct value and duration of symptoms are strongly associated with mortality. These 2 factors add useful information for clinicians to risk stratify patients presenting with COVID-19.
    Language English
    Publishing date 2021-01-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofab003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Encephalopathy and bilateral thalamic lesions in a child with MIS-C associated with COVID-19.

    Abel, Dori / Shen, Min Ye / Abid, Zaynah / Hennigan, Claire / Boneparth, Alexis / Miller, Emily Happy / Uhlemann, Anne-Catrin / McBrian, Danielle K / Thakur, Kiran / Silver, Wendy / Bain, Jennifer M

    Neurology

    2020  Volume 95, Issue 16, Page(s) 745–748

    MeSH term(s) Betacoronavirus ; Brain Diseases/pathology ; Brain Diseases/virology ; COVID-19 ; Child, Preschool ; Coronavirus Infections/pathology ; Humans ; Male ; Pandemics ; Pneumonia, Viral/pathology ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/pathology ; Thalamus/pathology
    Keywords covid19
    Language English
    Publishing date 2020-08-26
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000010652
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens

    Nuqui, Xandra / Casalino, Lorenzo / Zhou, Ling / Shehata, Mohamed / Wang, Albert / Tse, Alexandra L. / Ojha, Anupam / Kearns, Fiona L. / Rosenfeld, Mia A. / Miller, Emily Happy / Acreman, Cory M. / Ahn, Surl-Hee / Chandran, Kartik / McLellan, Jason S. / Amaro, Rommie E

    bioRxiv

    Abstract: The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 ... ...

    Abstract The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, the usage of S2 as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design highly stable S2-only antigens retaining a closed prefusion conformation. Weighted ensemble simulations provide mechanistic characterization of the S2 trimer opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Alchemical free energy perturbation calculations and a corroborating set of experiments confirm that V991W and T998W in the central helices of S2 stabilize the trimer in the closed prefusion conformation, producing an antigen with increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.
    Keywords covid19
    Language English
    Publishing date 2023-10-25
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.10.24.563841
    Database COVID19

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  6. Article ; Online: Oral Microbiome Alterations and SARS-CoV-2 Saliva Viral Load in Patients with COVID-19.

    Miller, Emily Happy / Annavajhala, Medini K / Chong, Alexander M / Park, Heekuk / Nobel, Yael R / Soroush, Ali / Blackett, John W / Krigel, Anna / Phipps, Meaghan M / Freedberg, Daniel E / Zucker, Jason / Sano, Ellen D / Uhlemann, Anne-Catrin / Abrams, Julian A

    Microbiology spectrum

    2021  Volume 9, Issue 2, Page(s) e0005521

    Abstract: Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to ...

    Abstract Bacterial-viral interactions in saliva have been associated with morbidity and mortality for respiratory viruses such as influenza and SARS-CoV. However, such transkingdom relationships during SARS-CoV-2 infection are currently unknown. Here, we aimed to elucidate the relationship between saliva microbiota and SARS-CoV-2 in a cohort of newly hospitalized COVID-19 patients and controls. We used 16S rRNA sequencing to compare microbiome diversity and taxonomic composition between COVID-19 patients (
    MeSH term(s) Bacteria/classification ; Bacteria/genetics ; COVID-19/pathology ; Dysbiosis/microbiology ; Female ; Humans ; Male ; Microbial Interactions/physiology ; Microbiota/genetics ; Middle Aged ; Nasopharynx/microbiology ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2/isolation & purification ; Saliva/microbiology ; Viral Load
    Chemical Substances RNA, Ribosomal, 16S
    Language English
    Publishing date 2021-10-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/Spectrum.00055-21
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  7. Article: Cerebrospinal Analysis in Patients With COVID-19.

    Miller, Emily Happy / Namale, Vivian S / Kim, Carla / Dugue, Rachelle / Waldrop, Greer / Ciryam, Prajwal / Chong, Alexander M / Zucker, Jason / Miller, Eliza C / Bain, Jennifer M / Willey, Joshua Z / Doyle, Kevin / Boehme, Amelia / Claassen, Jan / Uhlemann, Anne-Catrin / Thakur, Kiran T

    Open forum infectious diseases

    2020  Volume 7, Issue 11, Page(s) ofaa501

    Abstract: Background: Assessment of the impact of cerebrospinal fluid (CSF) analysis including investigation for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the optimization of patient care.: Methods: In this ... ...

    Abstract Background: Assessment of the impact of cerebrospinal fluid (CSF) analysis including investigation for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the optimization of patient care.
    Methods: In this case series, we review patients diagnosed with SARS-CoV-2 undergoing lumbar puncture (LP) admitted to Columbia University Irving Medical Center (New York, NY, USA) from March 1 to May 26, 2020. In a subset of patients, CSF SARS-CoV-2 quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) testing is performed.
    Results: The average age of 27 patients who underwent LP with definitive SARS-CoV-2 (SD) was 37.5 (28.7) years. CSF profiles showed elevated white blood cell counts and protein in 44% and 52% of patients, respectively. LP results impacted treatment decisions in 10 (37%) patients, either by change of antibiotics, influence in disposition decision, or by providing an alternative diagnosis. CSF SARS-CoV-2 qRT-PCR was performed on 8 (30%) patients, with negative results in all samples.
    Conclusions: Among patients diagnosed with SARS-CoV-2, CSF results changed treatment decisions or disposition in over one-third of our patient cohort. CSF was frequently abnormal, though CSF SARS-CoV-2 qRT-PCR was negative in all samples. Further studies are required to define whether CSF SARS-CoV-2 testing is warranted in certain clinical contexts.
    Language English
    Publishing date 2020-10-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2757767-3
    ISSN 2328-8957
    ISSN 2328-8957
    DOI 10.1093/ofid/ofaa501
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  8. Article: Encephalopathy and bilateral thalamic lesions in a child with MIS-C associated with COVID-19

    Abel, Dori / Shen, Min Ye / Abid, Zaynah / Hennigan, Claire / Boneparth, Alexis / Miller, Emily Happy / Uhlemann, Anne-Catrin / McBrian, Danielle K / Thakur, Kiran / Silver, Wendy / Bain, Jennifer M

    Neurology

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #733014
    Database COVID19

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  9. Article ; Online: Encephalopathy and bilateral thalamic lesions in a child with MIS-C associated with COVID-19

    Abel, Dori / Shen, Min Ye / Abid, Zaynah / Hennigan, Claire / Boneparth, Alexis / Miller, Emily Happy / Uhlemann, Anne-Catrin / McBrian, Danielle K. / Thakur, Kiran / Silver, Wendy / Bain, Jennifer M.

    Neurology

    2020  Volume 95, Issue 16, Page(s) 745–748

    Keywords Clinical Neurology ; covid19
    Language English
    Publisher Ovid Technologies (Wolters Kluwer Health)
    Publishing country us
    Document type Article ; Online
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/wnl.0000000000010652
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    In stock of ZB MED Cologne/Königswinter

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  10. Article: Cerebrospinal Fluid (CSF) Analysis in Patients with COVID-19

    Miller, Emily Happy / Namale, Vivian S. / Kim, Carla / Dugue, Rachelle / Waldrop, Greer / Ciryam, Prajwal / Chong, Alexander M. / Zucker, Jason / Miller, Eliza C. / Bain, Jennifer M. / Willey, Joshua Z. / Doyle, Kevin / Boehme, Amelia / Claassen, Jan / Uhlemann, Anne-Catrin / Thakur, Kiran T.

    Open Forum Infectious Diseases

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #873055
    Database COVID19

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