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

Autor:	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., 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., 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., Kays KR; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., Guess JR; Olink Proteomics, Watertown, MA, USA., Gentili M; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Fenyves BG; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Emergency Medicine, Semmelweis University, Budapest, Hungary., Charland NC; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., 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., Khanna HK; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., Lavin-Parsons KM; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., Lilley BM; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., Lodenstein CL; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., Margolin JD; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., McKaig BN; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., 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., 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., 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., 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., 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., Heimberg GS; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., 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., Lieb DJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Lin B; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., Pelka K; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., 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., Smillie CS; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA., Waghray A; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., 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., Jennings LL; Novartis Institutes for BioMedical Research, Cambridge, MA, USA., Grundberg I; Olink Proteomics, Watertown, MA, USA., 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., Parry BA; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA., 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., 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., 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., 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.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2021 May 18; Vol. 2 (5), pp. 100287. Date of Electronic Publication: 2021 May 03.
DOI:	10.1016/j.xcrm.2021.100287
Abstrakt:	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. Competing Interests: 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. (© 2021 The Authors.)
Databáze:	MEDLINE
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