期刊
CELL
卷 183, 期 6, 页码 1479-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.10.037
关键词
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资金
- Wilke Family Foundation
- Murdock Trust
- Gilead Sciences
- Swedish Medical Center Foundation
- Parker Institute for Cancer Immunotherapy
- Merck
- Biomedical Advanced Research and Development Authority [HHSO10201600031C]
- DOD [W911NF-17-2-0086]
- NIH [AI068129, R21 AI138258, R01 DA040395, UG3TR002884]
- National Center For Advancing Translational Sciences of the NIH [OT2 TR003443]
- NIH Human Immunology Project Consortium [U19AI128914]
- Vaccine and Immunology Statistical Center (Bill and Melinda Gates Foundation) [OPP1032317]
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-CoV2. 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.
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