Cell Reports Medicine (May 2021)
Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions
- Michael R. Filbin,
- Arnav Mehta,
- Alexis M. Schneider,
- Kyle R. Kays,
- Jamey R. Guess,
- Matteo Gentili,
- Bánk G. Fenyves,
- Nicole C. Charland,
- Anna L.K. Gonye,
- Irena Gushterova,
- Hargun K. Khanna,
- Thomas J. LaSalle,
- Kendall M. Lavin-Parsons,
- Brendan M. Lilley,
- Carl L. Lodenstein,
- Kasidet Manakongtreecheep,
- Justin D. Margolin,
- Brenna N. McKaig,
- Maricarmen Rojas-Lopez,
- Brian C. Russo,
- Nihaarika Sharma,
- Jessica Tantivit,
- Molly F. Thomas,
- Robert E. Gerszten,
- Graham S. Heimberg,
- Paul J. Hoover,
- David J. Lieb,
- Brian Lin,
- Debby Ngo,
- Karin Pelka,
- Miguel Reyes,
- Christopher S. Smillie,
- Avinash Waghray,
- Thomas E. Wood,
- Amanda S. Zajac,
- Lori L. Jennings,
- Ida Grundberg,
- Roby P. Bhattacharyya,
- Blair Alden Parry,
- Alexandra-Chloé Villani,
- Moshe Sade-Feldman,
- Nir Hacohen,
- Marcia B. Goldberg
Affiliations
- Michael R. Filbin
- 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; Corresponding author
- Arnav Mehta
- 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; Corresponding author
- Alexis M. Schneider
- 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
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Jamey R. Guess
- Olink Proteomics, Watertown, MA, USA
- Matteo Gentili
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA
- Bánk G. Fenyves
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Emergency Medicine, Semmelweis University, Budapest, Hungary
- Nicole C. Charland
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Anna L.K. Gonye
- 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
- 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
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Thomas J. LaSalle
- 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
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Brendan M. Lilley
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Carl L. Lodenstein
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Kasidet Manakongtreecheep
- 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
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Brenna N. McKaig
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Maricarmen Rojas-Lopez
- 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
- 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
- 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
- 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
- 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
- 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
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA
- Paul J. Hoover
- 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
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA
- Brian Lin
- Department of Medicine, Harvard Medical School, Boston, MA, USA; Center for Regenerative Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Debby Ngo
- 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
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA
- Miguel Reyes
- 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
- Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA
- Avinash Waghray
- 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
- 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
- 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
- Novartis Institutes for BioMedical Research, Cambridge, MA, USA
- Ida Grundberg
- Olink Proteomics, Watertown, MA, USA
- Roby P. Bhattacharyya
- 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
- Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA
- Alexandra-Chloé Villani
- 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
- 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
- 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; Corresponding author
- Marcia B. Goldberg
- 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; Corresponding author
- Journal volume & issue
-
Vol. 2,
no. 5
p. 100287
Abstract
Summary: 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.
