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

ABSTRACT: 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.

SUBMITTER: Szabo PA

PROVIDER: S-EPMC7951561 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Szabo Peter A PA Dogra Pranay P Gray Joshua I JI Wells Steven B SB Connors Thomas J TJ Weisberg Stuart P SP Krupska Izabela I Matsumoto Rei R Poon Maya M L MML Idzikowski Emma E Morris Sinead E SE Pasin Chloé C Yates Andrew J AJ Ku Amy A Chait Michael M Davis-Porada Julia J Guo Xinzheng V XV Zhou Jing J Steinle Matthew M Mackay Sean S Saqi Anjali A Baldwin Matthew R MR Sims Peter A PA Farber Donna L DL

Immunity 20210311 4

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 ...[more]

PMID: 33765436

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Dataset Information

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

Publications

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

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