ArticleCell reports2021
Metabolic programs define dysfunctional immune responses in severe COVID-19 patients.
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Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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96citing papers in PubMed, 1 pooled it
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-analysis of single-cell RNA-seq data reveals phenotypic switching of immune cells in severe COVID-19 patients.Computers in biology and medicine · 2021Pooled it
- Trial
- Cognition-Linked Monocyte State Reveals Altered Myeloid-Lymphoid Coordination in Neuro-PASC.International journal of molecular sciences · 2026Article
- Post-COVID impairment of T cell responses to community-acquired pathogens can be modified by activating cellular metabolism.PLoS pathogens · 2026Article
- Delirium in hospitalized COVID-19 patients is associated with dynamic changes in peripheral immune gene expression.GeroScience · 2026Article
- A Post-GWAS Analysis of the Shared Genetic Architecture Between COVID-19 and Coronary Artery Disease.International journal of molecular sciences · 2026Article
- Targeting VDAC1 to protect against mitochondria-linked cell death pathways: apoptosis, pyroptosis, ferroptosis, and associated diseases.Apoptosis : an international journal on programmed cell death · 2026Article
- Article
- The neutrophil-to-lymphocyte ratio as a marker of immunosenescence and COVID-19 outcomes in the elderly: A narrative review.Physiological reports · 2026Review
- Post-COVID impairment of memory T cell responses to community-acquired pathogens can be rectified by activating cellular metabolism.bioRxiv : the preprint server for biology · 2026Article
- The inflammation-immunosuppression loop as a driver of immune dysfunction and secondary infections in severe COVID-19.Frontiers in immunology · 2026Review
- Article
- Nicheformer: a foundation model for single-cell and spatial omics.Nature methods · 2025Article
- Metformin-Induced Apoptosis Is Mediated Through Mitochondrial VDAC1.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Comparison of the Human Plasma Peptides from the Fit of Fragmentation Spectra versus Accurate Monoisotopic Precursor Mass.ACS omega · 2025Article
- Peripheral blood mononuclear cell transcriptomic trajectories reveal dynamic regulation of inflammatory actors in delirium.medRxiv : the preprint server for health sciences · 2025Article
- Longitudinal Characterization of SARS-CoV-2 Immunity in Hemodialysis Patients Post Omicron.Kidney international reports · 2025Article
- Distinct myeloid-derived suppressor cell populations in human glioblastoma.Science (New York, N.Y.) · 2025Article
- Personalized immunization to optimize vaccine immunogenicity: exploring the multidimensional effects of host intrinsic factors, external intervention strategies, and the external environment.Frontiers in immunology · 2025Review
- The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.Frontiers in immunology · 2025Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors.
Elizabeth A ThompsonDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Katherine CascinoDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Alvaro A OrdonezDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Weiqiang ZhouDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
Ajay VaghasiaDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Anne Hamacher-BradyW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
Nathan R BradyW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
Im-Hong SunDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Rulin WangDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Avi Z RosenbergDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Michael DelannoyDepartment of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Richard RothmanDepartment of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Katherine FenstermacherDepartment of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Lauren SauerDepartment of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Kathyrn Shaw-SalibaDepartment of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Evan M BlochDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Andrew D ReddDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Baltimore, MD 21205, USA.
Aaron A R TobianDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Maureen HortonDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Kellie SmithDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Andrew PekoszW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
Franco R D'AlessioDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Srinivasan YegnasubramanianDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Hongkai JiDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA.
Andrea L CoxDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21287, USA. Electronic address: acox@jhmi.edu.
Jonathan D PowellDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: jpowell@jhmi.edu.
Funding
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MInternational Studies of the Acquired Immune Deficiency Syndrome (AIDS)ZIAAI000361 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI REDD, ANDREW · 2009 to 2025
$15.8MTR&D Project 3P41EB028239 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI JONATHAN P SCHNECK · 2019 to 2026
$11.5MScientific CoreU19AI088791 · NIAID · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 2010 to 2020
$8.2MUnlocking the Potential of HIV-Infected Deceased Donors for Organ TransplantationR01AI120938 · NIAID · JOHNS HOPKINS UNIVERSITY · PI TOBIAN, AARON A · 2016 to 2021
$4.3MPreclinical modeling to study Tuberculous MeningitisR01AI145435 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$4.0MMeasuring Intralesional Drug Exposures in Cavitary TB using Noninvasive In Vivo PET ImagingR01AI153349 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY · 2020 to 2024
$3.8MPenile Microbiome, Inflammation and HIV Susceptibility During Sexual Debut and Maturation Among Male AdolescentsR01AI128779 · NIAID · JOHNS HOPKINS UNIVERSITY · PI TOBIAN, AARON A · 2017 to 2020
$2.1MBig Data Methods for Decoding Gene RegulationR01HG009518 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI JI, HONGKAI · 2018 to 2021
$1.7MMeasuring Intralesional Bedaquiline Exposures in Cavitary TB Using Noninvasive In Vivo PET ImagingR21AI149760 · NIAID · JOHNS HOPKINS UNIVERSITY · PI JAIN, SANJAY, ORDONEZ, ALVARO ANDRES · 2020 to 2021
$450kLSM880 Laser-scanning Microscope with Airyscan ModuleS10OD023548 · OD · JOHNS HOPKINS UNIVERSITY · PI KUO, SCOT CHARLES · 2018 to 2018
$439kEpidemiologic and Immunologic Investigations of SARS-CoV-2 (COVID-19) InfectionsZIAAI001286 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI QUINN, THOMAS · 2020 to 2023
$349kNCATS NIH HHS UL1 TR001079NHGRI NIH HHS R01 HG009518NIAID NIH HHS HHSN272201400007CNIAID NIH HHS R01 AI120938NIAID NIH HHS R01 AI128779NIAID NIH HHS R01 AI145435NIAID NIH HHS R01 AI153349NIAID NIH HHS R21 AI149760NIAID NIH HHS U19 AI088791NIBIB NIH HHS P41 EB028239NIH HHS S10 OD023548
Abstract
It is unclear why some SARS-CoV-2 patients readily resolve infection while others develop severe disease. By interrogating metabolic programs of immune cells in severe and recovered coronavirus disease 2019 (COVID-19) patients compared with other viral infections, we identify a unique population of T cells. These T cells express increased Voltage-Dependent Anion Channel 1 (VDAC1), accompanied by gene programs and functional characteristics linked to mitochondrial dysfunction and apoptosis. The percentage of these cells increases in elderly patients and correlates with lymphopenia. Importantly, T cell apoptosis is inhibited in vitro by targeting the oligomerization of VDAC1 or blocking caspase activity. We also observe an expansion of myeloid-derived suppressor cells with unique metabolic phenotypes specific to COVID-19, and their presence distinguishes severe from mild disease. Overall, the identification of these metabolic phenotypes provides insight into the dysfunctional immune response in acutely ill COVID-19 patients and provides a means to predict and track disease severity and/or design metabolic therapeutic regimens.
Indexed as
AdultAgedAged, 80 and overApoptosisCaspasesCOVID-19FemaleHumansImmunityLymphopeniaMaleMiddle AgedMitochondriaMyeloid-Derived Suppressor CellsSARS-CoV-2T-LymphocytesCaspasesVoltage-Dependent Anion Channel 1apoptosisCOVID-19immunologyimmunometabolismMDSCsmetabolismmitochondriaSARS-CoV-2T cells
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