tetano
Editor, Senior Moderator
Immunity
. 2021 Mar 11;S1074-7613(21)00117-5.
doi: 10.1016/j.immuni.2021.03.005. Online ahead of print.
Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19
Peter A Szabo[SUP] 1 [/SUP], Pranay Dogra[SUP] 1 [/SUP], Joshua I Gray[SUP] 1 [/SUP], Steven B Wells[SUP] 2 [/SUP], Thomas J Connors[SUP] 3 [/SUP], Stuart P Weisberg[SUP] 4 [/SUP], Izabela Krupska[SUP] 2 [/SUP], Rei Matsumoto[SUP] 5 [/SUP], Maya M L Poon[SUP] 6 [/SUP], Emma Idzikowski[SUP] 3 [/SUP], Sinead E Morris[SUP] 4 [/SUP], Chlo? Pasin[SUP] 4 [/SUP], Andrew J Yates[SUP] 4 [/SUP], Amy Ku[SUP] 4 [/SUP], Michael Chait[SUP] 4 [/SUP], Julia Davis-Porada[SUP] 7 [/SUP], Xinzheng V Guo[SUP] 8 [/SUP], Jing Zhou[SUP] 9 [/SUP], Matthew Steinle[SUP] 9 [/SUP], Sean Mackay[SUP] 9 [/SUP], Anjali Saqi[SUP] 4 [/SUP], Matthew R Baldwin[SUP] 10 [/SUP], Peter A Sims[SUP] 11 [/SUP], Donna L Farber[SUP] 12 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
Keywords: ARDS; COVID-19; chemokines; coronavirus disease 2019; cytokines; lung immunity; macrophages; monocytes; single-cell RNA sequencing; tissue resident memory T cells.
. 2021 Mar 11;S1074-7613(21)00117-5.
doi: 10.1016/j.immuni.2021.03.005. Online ahead of print.
Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19
Peter A Szabo[SUP] 1 [/SUP], Pranay Dogra[SUP] 1 [/SUP], Joshua I Gray[SUP] 1 [/SUP], Steven B Wells[SUP] 2 [/SUP], Thomas J Connors[SUP] 3 [/SUP], Stuart P Weisberg[SUP] 4 [/SUP], Izabela Krupska[SUP] 2 [/SUP], Rei Matsumoto[SUP] 5 [/SUP], Maya M L Poon[SUP] 6 [/SUP], Emma Idzikowski[SUP] 3 [/SUP], Sinead E Morris[SUP] 4 [/SUP], Chlo? Pasin[SUP] 4 [/SUP], Andrew J Yates[SUP] 4 [/SUP], Amy Ku[SUP] 4 [/SUP], Michael Chait[SUP] 4 [/SUP], Julia Davis-Porada[SUP] 7 [/SUP], Xinzheng V Guo[SUP] 8 [/SUP], Jing Zhou[SUP] 9 [/SUP], Matthew Steinle[SUP] 9 [/SUP], Sean Mackay[SUP] 9 [/SUP], Anjali Saqi[SUP] 4 [/SUP], Matthew R Baldwin[SUP] 10 [/SUP], Peter A Sims[SUP] 11 [/SUP], Donna L Farber[SUP] 12 [/SUP]
Affiliations
- PMID: 33765436
- DOI: 10.1016/j.immuni.2021.03.005
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[SUP]+[/SUP] 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.
Keywords: ARDS; COVID-19; chemokines; coronavirus disease 2019; cytokines; lung immunity; macrophages; monocytes; single-cell RNA sequencing; tissue resident memory T cells.