Journal
NATURE
Volume 590, Issue 7847, Pages 635-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-020-03148-w
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Funding
- NCI Cancer Center Support Grant [P30 CA060553]
- NIH [1S10OD011996-01, T32AG020506-18, U19AI135964, P01AG049665, P01AG04966506S1, R01HL147575, GM129312, HL134800, R56HL135124, R01HL153312, K08HL128867, R01HL149883]
- Feinberg School of Medicine
- Center for Genetic Medicine
- Feinberg's Department of Biochemistry and Molecular Genetics
- Office of the Provost
- Office for Research
- Northwestern Information Technology
- Simpsons Querrey Institute for Epigenetics
- Veterans Affairs [I01CX001777]
- NUCATS COVID-19 Rapid Response Grant
- [T32HL076139]
- [F32HL151127]
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The study found that patients infected with SARS-CoV-2 have enriched T cells and monocytes in the alveolar space, suggesting that the virus infects alveolar macrophages and induces T cell production of interferon-, leading to inflammation and persistent alveolitis.
Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-. to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.
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