Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.

ARDS COVID-19 severity T cell activation acute respiratory distress syndrome death versus survival intracellular death signatures longitudinal lung epithelial cells lung monocyte/macrophages pancreatic exocrine proteases plasma proteomics

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
18 05 2021
Historique:
received: 22 12 2020
revised: 08 03 2021
accepted: 23 04 2021
pubmed: 11 5 2021
medline: 11 5 2021
entrez: 10 5 2021
Statut: ppublish

Résumé

Mechanisms underlying severe coronavirus disease 2019 (COVID-19) disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNA-seq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune-cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell-type-specific intracellular death signatures, cellular angiotensin-converting enzyme 2 (ACE2) expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

Identifiants

DOI: 10.1016/j.xcrm.2021.100287 PMID: 33969320 PMC: PMC8091031
pubmed: 33969320
doi: 10.1016/j.xcrm.2021.100287
pii: S2666-3791(21)00115-4
pmc: PMC8091031
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Pagination

100287

Subventions

Organisme : NIAID NIH HHS
ID : T32 AI007061
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002541
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI082630
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001102
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA071345
Pays : United States

Commentaires et corrections

Type : UpdateOf

Informations de copyright

© 2021 The Authors.

Déclaration de conflit d'intérêts

A.M. is a consultant for Third Rock Ventures. J.R.G. and I. Gushterova are employees of Olink Proteomics. G.S.H. is an employee of Genentech (as of November 2020). L.L.J. is an employee and stockholder of Novartis. N.H. holds equity in BioNTech and is a consultant for Related Sciences.

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Auteurs

Michael R Filbin (MR)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Arnav Mehta (A)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.

Alexis M Schneider (AM)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Kyle R Kays (KR)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Jamey R Guess (JR)

Olink Proteomics, Watertown, MA, USA.

Matteo Gentili (M)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Bánk G Fenyves (BG)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Emergency Medicine, Semmelweis University, Budapest, Hungary.

Nicole C Charland (NC)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Anna L K Gonye (ALK)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Irena Gushterova (I)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Hargun K Khanna (HK)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Thomas J LaSalle (TJ)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Kendall M Lavin-Parsons (KM)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Brendan M Lilley (BM)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Carl L Lodenstein (CL)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Kasidet Manakongtreecheep (K)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Justin D Margolin (JD)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Brenna N McKaig (BN)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Maricarmen Rojas-Lopez (M)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.

Brian C Russo (BC)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.

Nihaarika Sharma (N)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Jessica Tantivit (J)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Molly F Thomas (MF)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Robert E Gerszten (RE)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
CardioVascular Institute, Department of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Graham S Heimberg (GS)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Paul J Hoover (PJ)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.

David J Lieb (DJ)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Brian Lin (B)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Debby Ngo (D)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Karin Pelka (K)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Miguel Reyes (M)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Christopher S Smillie (CS)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.

Avinash Waghray (A)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Thomas E Wood (TE)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.

Amanda S Zajac (AS)

Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.

Lori L Jennings (LL)

Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

Ida Grundberg (I)

Olink Proteomics, Watertown, MA, USA.

Roby P Bhattacharyya (RP)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Blair Alden Parry (BA)

Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.

Alexandra-Chloé Villani (AC)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

Moshe Sade-Feldman (M)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.

Nir Hacohen (N)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.

Marcia B Goldberg (MB)

Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Classifications MeSH