Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine...

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Published in:Immunity (Cambridge, Mass.) Mass.), 2021-04, Vol.54 (4), p.797-814.e6
Main Authors: Szabo, Peter A., Dogra, Pranay, Gray, Joshua I., Wells, Steven B., Connors, Thomas J., Weisberg, Stuart P., Krupska, Izabela, Matsumoto, Rei, Poon, Maya M.L., Idzikowski, Emma, Morris, Sinead E., Pasin, Chloé, Yates, Andrew J., Ku, Amy, Chait, Michael, Davis-Porada, Julia, Guo, Xinzheng V., Zhou, Jing, Steinle, Matthew, Mackay, Sean, Saqi, Anjali, Baldwin, Matthew R., Sims, Peter A., Farber, Donna L.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age
Age Factors
Aged
Aged, 80 and over
Alveoli
Antibodies
ARDS
Blood
CCR2 protein
CD163 antigen
Cell survival
Chemokines
Chemotactic factors
coronavirus disease 2019
Coronaviruses
COVID-19
COVID-19 - blood
COVID-19 - immunology
COVID-19 - mortality
COVID-19 - pathology
Cytokines
Cytokines - immunology
Cytokines - metabolism
Enrollments
Flow cytometry
Humans
Immune response
Immune system
Infections
Inflammation
Intubation
Longitudinal Studies
Lung - immunology
Lung - pathology
lung immunity
Lungs
Lymphocytes
Lymphocytes T
macrophages
Macrophages - immunology
Macrophages - pathology
Middle Aged
Monocyte chemoattractant protein 1
Monocytes
Monocytes - immunology
Monocytes - pathology
Mortality
Myeloid cells
Myeloid Cells - immunology
Myeloid Cells - pathology
Pathogenesis
Patients
Respiratory tract
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
single-cell RNA sequencing
T-Lymphocytes - immunology
T-Lymphocytes - pathology
tissue resident memory T cells
Transcriptome
Viral diseases
Young Adult
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Summary:Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract. [Display omitted] •Airways show localized immune responses correlating to age and outcome in COVID-19•Airway T cells are activated and resident, while myeloid cells are hyperinflammatory•Aberrant CD163hi and HLA-DRlo monocytes predominate in COVID-19 blood•Monocytes infiltrate airways and lung alveoli potentially through a CCL2-CCR2 axis Through longitudinal profiling of paired airways and blood from patients with severe COVID-19, Szabo et al. reveal airway immune responses that correlate with age and outcome. They further identify coordinate roles for T and myeloid cells in the respiratory tract and circulation in perpetuating lung pathology and disease pathogenesis.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2021.03.005