Title
Longitudinal profiling of respiratory and systemic immune responses reveals myeloid cell-driven lung inflammation in severe COVID-19
Date Issued
13 April 2021
Access level
open access
Resource Type
journal article
Author(s)
Szabo P.A.
Dogra P.
Gray J.I.
Wells S.B.
Connors T.J.
Weisberg S.P.
Krupska I.
Matsumoto R.
Poon M.M.L.
Idzikowski E.
Morris S.E.
Pasin C.
Yates A.J.
Ku A.
Chait M.
Davis-Porada J.
Guo X.V.
Zhou J.
Steinle M.
Mackay S.
Saqi A.
Sims P.A.
Farber D.L.
IsoPlexis
Publisher(s)
Elsevier
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.
Start page
797
End page
814.e6
Volume
54
Issue
4
Language
English
OCDE Knowledge area
Inmunología
Subjects
Scopus EID
2-s2.0-85103088862
PubMed ID
Source
Immunity
ISSN of the container
1074-7613
Sponsor(s)
We wish to express our gratitude to the medical ICU nurse champions Cora Garcellano, Tenzin Drukdak, Harriet Avila Raymundo, Lori Wagner, and Ricky Lee, who led the efforts to obtain patient samples for the severe COVID-19 patients; to Evelyn Hernandez and Lorena Gomez for their roles as clinical coordinators; and to the nurses and clinical staff in the Pediatric Intensive Care Unit of MSCHONY. We acknowledge the dedication, commitment, and sacrifice of the other nurses, providers, and personnel who helped care for these patients during the COVID-19 crisis. We acknowledge the suffering and loss of our COVID-19 patients and of their families and our community. We gratefully acknowledge the generosity of the donor families and the exceptional efforts of LiveOnNY transplant coordinators and staff for the organ donor lungs. This work was supported by NIH grants AI128949 and AI06697 awarded to D.L.F., a Chan Zuckerberg Initiative COVID-19 grant to D.L.F. and P.A. Sims, and AI093870 and AI150680 awarded to A.J.Y. P.D. was supported by a CRI-Irvington Postdoctoral Fellowship , and P.A. Szabo was supported by a Canadian Institutes of Health Research Fellowship . T.J.C. is supported by NIH K23 A1141686 , and S.P.W. is supported by NIH K08 DK122130 . Research reported in this publication was performed in the Human Immune Monitoring Core, the Columbia Single Cell Analysis Core, and the Sulzberger Columbia Genome Center, which are supported by NCI cancer center support grant P30CA013696 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Eldad Hod for the use of his laboratory for sample processing, and Carly Ziegler and Dr. Alex Shalek of MIT for sharing their merged human SARS-CoV-2 genome and transcriptome annotation.
We wish to express our gratitude to the medical ICU nurse champions Cora Garcellano, Tenzin Drukdak, Harriet Avila Raymundo, Lori Wagner, and Ricky Lee, who led the efforts to obtain patient samples for the severe COVID-19 patients; to Evelyn Hernandez and Lorena Gomez for their roles as clinical coordinators; and to the nurses and clinical staff in the Pediatric Intensive Care Unit of MSCHONY. We acknowledge the dedication, commitment, and sacrifice of the other nurses, providers, and personnel who helped care for these patients during the COVID-19 crisis. We acknowledge the suffering and loss of our COVID-19 patients and of their families and our community. We gratefully acknowledge the generosity of the donor families and the exceptional efforts of LiveOnNY transplant coordinators and staff for the organ donor lungs. This work was supported by NIH grants AI128949 and AI06697 awarded to D.L.F. a Chan Zuckerberg Initiative COVID-19 grant to D.L.F. and P.A. Sims, and AI093870 and AI150680 awarded to A.J.Y. P.D. was supported by a CRI-Irvington Postdoctoral Fellowship, and P.A. Szabo was supported by a Canadian Institutes of Health Research Fellowship. T.J.C. is supported by NIH K23 A1141686, and S.P.W. is supported by NIH K08 DK122130. Research reported in this publication was performed in the Human Immune Monitoring Core, the Columbia Single Cell Analysis Core, and the Sulzberger Columbia Genome Center, which are supported by NCI cancer center support grant P30CA013696. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Eldad Hod for the use of his laboratory for sample processing, and Carly Ziegler and Dr. Alex Shalek of MIT for sharing their merged human SARS-CoV-2 genome and transcriptome annotation. P.A. Szabo, S.B.W. J.I.G. and P.D. processed samples, designed and optimized high-dimensional flow cytometry panels, analyzed data, made figures, and wrote the manuscript. P.A. Szabo and S.B.W. processed samples for scRNA-seq profiling and encapsulation using 10X Chromium; I.K. prepared and sequenced the 10X libraries. P.D. designed the Python pipeline for flow cytometry data. M.R.B. monitored and consented the intensive care unit (ICU) patients, oversaw the clinical data analysis, and collected samples. T.J.C. obtained and maintained the institutional review board (IRB) protocols, consented patients, and processed samples. M.M.L.P. R.M. E.I. and M.C. obtained and processed the patient samples. S.E.M. C.P. and A.J.Y. statistically analyzed the longitudinal data and performed the k-means clustering analysis. J.D.-P. captured and analyzed the patient data. J.Z. M.S. and S.M. performed the cytokine analysis of airway supernatants and blood plasma. S.P.W. planned, designed, and analyzed the lung autopsy imaging experiments. A.S. provided the lung autopsy samples and associated data. A.K. performed the immunohistochemistry of lung autopsies. P.A. Sims planned the scRNA-seq experiments, analyzed the data, and wrote and edited the manuscript. D.L.F. oversaw the compliance, planned the experiments, coordinated the sample acquisition and data acquisition/analysis, analyzed the data, and wrote and edited the paper. J.Z. M.S. and S.M. have competing interests with IsoPlexis. The remaining authors declare no competing interests.
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