Journal
IMMUNITY
Volume 53, Issue 6, Pages 1296-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2020.11.017
Keywords
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Funding
- German Research Foundation (DFG) [07495230, ExC 2167, CRC1182 C2]
- IMI2 Project [3TR]
- Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany (sparse2big)
- EU projects SYSCID [733100]
- DZIF, Germany [TTU 04.816, 04.817]
- Hector Foundation [M89]
- DFG [ExC 2167, EXC 2124-390838134, CRC 1182]
- German Center for Infection Research (DZIF) [8020708703]
- [INST 37/1049-1]
- [INST 216/981-1]
- [INST 257/605-1]
- [INST 269/768-1]
- [INST 217/988-1]
- [INST 217/577-1]
- [EXC2151/1 (390873048)]
- [SFB TR57]
- [SPP1937]
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Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.
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