Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19
| Autor: | Jenn J. Hadlock, Michael Zager, Rachel Liu, Daniel Chen, Valentin Voillet, Kim Murray, Alan Aderem, Yapeng Su, Jongchan Choi, Philip D. Greenberg, Rongyu Zhang, Yong Zhou, Sui Huang, Alexander M. Xu, Lesley Jones, Raphael Gottardo, Guangrong Qin, Dan Yuan, Chengzhen L. Dai, Jing Zhou, Heather A. Algren, Rick Edmark, Kelsey Scherler, Alissa C. Rothchild, Christopher Lausted, Venkata R Duvvuri, Clifford Rostomily, Naeha Subramanian, Christopher R. Dale, Mark M. Davis, Lewis L. Lanier, Jeffrey A. Bluestone, Jingyi Xie, Sarah Li, Ryan Roper, Jing Li, Brett Smith, Andrew T. Magis, John C. Earls, Sunga Hong, Julie A. Wallick, Sean Mackay, Lee Rowen, Leroy Hood, Priyanka Baloni, Jason D Goldman, Nathan D. Price, James R. Heath, John E. Heath, D. Shane O’Mahony, Sergey A. Kornilov, Shen Dong, Pamela Troisch, Wei Wei, Kai Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Adolescent Cell Disease Biology Severity of Illness Index Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system Single-cell analysis Severity of illness medicine Humans RNA-Seq Aged 030304 developmental biology Aged 80 and over 0303 health sciences Innate immune system SARS-CoV-2 COVID-19 Genomics Middle Aged Phenotype medicine.anatomical_structure Immunology Female Single-Cell Analysis 030217 neurology & neurosurgery Blood drawing |
| Zdroj: | Cell |
| ISSN: | 0092-8674 |
| Popis: | We present an integrated analysis of the clinical measurements, immune cells and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention. Highlights • Analysis of serial blood from 139 COVID-19 patients reveals immune coordination • A major immunological shift is seen between mild and moderate infection • Moderate and severe cases exhibit inflammation and a sharp drop in blood nutrients • Novel immune cell subsets emerge in moderate cases and increase with severity Using serial blood draws from hospitalized COVID-19 patients, Su et al. present an extensive single-cell multi-omics dataset covering the first week infection following clinical diagnosis, which includes information on plasma proteins, metabolites, transcriptomic data, immune receptor sequences, secreted proteins, and electronic health record data. Their integrated analysis identifies a major immunological shift between mild and moderate infection, which includes an increase in inflammation, drop in blood nutrients, and the emergence of novel immune cell subpopulations that intensify with disease severity. |
| Databáze: | OpenAIRE |
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