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Single-cell analysis of airway samples identifies immune cell activation correlating with COVID-19 disease severity

To investigate the immune response and mechanisms associated with severe COVID-19, we performed single-cell RNA-seq on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from 5 healthy controls. We identified airway epithelial cell types and states vulnerable to SARS-CoV-2 infection. In COVID-19 patients, epithelial cells showed an average threefold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells. Compared with moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand–receptor expression profiles, and activated immune cells , including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF . The transcriptional differences in critical cases compared with moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure. Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways may suppress immune hyperactivation in critical COVID-19.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006339 Illumina NovaSeq 6000 36
Publications Citations
COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Nat Biotechnol 38: 2020 970-979
A review of COVID-19 biomarkers and drug targets: resources and tools.
Brief Bioinform 22: 2021 701-713
Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19.
Signal Transduct Target Ther 6: 2021 292
Meta-analysis of COVID-19 single-cell studies confirms eight key immune responses.
Sci Rep 11: 2021 20833
Aging-related cell type-specific pathophysiologic immune responses that exacerbate disease severity in aged COVID-19 patients.
Aging Cell 21: 2022 e13544
Identification of Transcription Factors Regulating SARS-CoV-2 Tropism Factor Expression by Inferring Cell-Type-Specific Transcriptional Regulatory Networks in Human Lungs.
Viruses 14: 2022 837
Molecular imaging of chemokine-like receptor 1 (CMKLR1) in experimental acute lung injury.
Proc Natl Acad Sci U S A 120: 2023 e2216458120
sccomp: Robust differential composition and variability analysis for single-cell data.
Proc Natl Acad Sci U S A 120: 2023 e2203828120
Airway Basal Stem Cells in COVID-19 Exhibit a Proinflammatory Signature and Impaired Mucocililary Differentiation.
Am J Respir Cell Mol Biol 70: 2024 26-38
Bulk and Single-Cell RNA Sequencing Elucidate the Etiology of Severe COVID-19.
Int J Mol Sci 25: 2024 3280