Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21702-6
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Funding
- Fondazione Cariverona (ENACT Project)
- Fondazione TIM
- 10x Genomics Inc.
- Carlo Erba
- Merck KGaA, Darmstadt, Germany
- Chan Zuckerberg Initiative (CZI)
- ISF Israel Precision Medicine Program (IPMP) [607/20, P128245]
- HHMI International Scholar award
- European Research Council Consolidator Grant (ERC-COG) [724471]
- SCA award of the Wolfson Foundation and Family Charitable Trust
- Thompson Family Foundation
- MRA Established Investigator Award [509044]
- Israel Science Foundation [703/15]
- Ernest and Bonnie Beutler Research Program for Excellence in Genomic Medicine
- Helen and Martin Kimmel award
- NeuroMac DFG/Transregional Collaborative Research Center Grant, an International Progressive MS Alliance/NMSS [PA-1604 08459]
- Adelis Foundation grant
- Wolfson Family Charitable Trust
- Wolfson Foundation, ISF [3652/19]
- European Research Council (ERC) [724471] Funding Source: European Research Council (ERC)
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COVID-19 patients show unique immune features, including lung accumulation of naive lymphoid cells, systemic expansion and activation of myeloid cells, and immune suppression. Loss of monocyte-driven and neutrophil-driven immune suppression may lead to fatal outcomes in severe patients. On the other hand, a lung CXCR6(+) effector memory T cell subset may be associated with better prognosis in severe COVID-19 patients.
Since the beginning of the SARS-CoV-2 pandemic, COVID-19 appeared as a unique disease with unconventional tissue and systemic immune features. Here we show a COVID-19 immune signature associated with severity by integrating single-cell RNA-seq analysis from blood samples and broncho-alveolar lavage fluids with clinical, immunological and functional ex vivo data. This signature is characterized by lung accumulation of naive lymphoid cells associated with a systemic expansion and activation of myeloid cells. Myeloid-driven immune suppression is a hallmark of COVID-19 evolution, highlighting arginase-1 expression with immune regulatory features of monocytes. Monocyte-dependent and neutrophil-dependent immune suppression loss is associated with fatal clinical outcome in severe patients. Additionally, our analysis shows a lung CXCR6(+) effector memory T cell subset is associated with better prognosis in patients with severe COVID-19. In summary, COVID-19-induced myeloid dysregulation and lymphoid impairment establish a condition of 'immune silence' in patients with critical COVID-19. Integrated studies of matched tissue sites and cell types in COVID-19 patients are important to define the immune mechanisms of pathology. Here, the authors describe an immune signature in fatal COVID-19 patients harmonizing single-cell RNA sequencing of blood and matched BAL cells with deep clinical, immunological and functional data.
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