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Longitudinal proteomic analysis of severe COVID-19 reveals survival-associated signatures, tissue-specific cell death, and cell-cell interactions.
Filbin, Michael R; Mehta, Arnav; Schneider, Alexis M; Kays, Kyle R; Guess, Jamey R; Gentili, Matteo; Fenyves, Bánk G; Charland, Nicole C; Gonye, Anna L K; Gushterova, Irena; Khanna, Hargun K; LaSalle, Thomas J; Lavin-Parsons, Kendall M; Lilley, Brendan M; Lodenstein, Carl L; Manakongtreecheep, Kasidet; Margolin, Justin D; McKaig, Brenna N; Rojas-Lopez, Maricarmen; Russo, Brian C; Sharma, Nihaarika; Tantivit, Jessica; Thomas, Molly F; Gerszten, Robert E; Heimberg, Graham S; Hoover, Paul J; Lieb, David J; Lin, Brian; Ngo, Debby; Pelka, Karin; Reyes, Miguel; Smillie, Christopher S; Waghray, Avinash; Wood, Thomas E; Zajac, Amanda S; Jennings, Lori L; Grundberg, Ida; Bhattacharyya, Roby P; Parry, Blair Alden; Villani, Alexandra-Chloé; Sade-Feldman, Moshe; Hacohen, Nir; Goldberg, Marcia B.
  • Filbin MR; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Mehta A; Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
  • Schneider AM; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Kays KR; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Guess JR; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Gentili M; Massachusetts General Hospital Cancer Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Fenyves BG; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Charland NC; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Gonye ALK; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Gushterova I; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Khanna HK; Olink Proteomics, Watertown, MA, USA.
  • LaSalle TJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Lavin-Parsons KM; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Lilley BM; Department of Emergency Medicine, Semmelweis University, Budapest, Hungary.
  • 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.
  • Margolin JD; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • McKaig BN; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Rojas-Lopez M; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Russo BC; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Sharma N; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Tantivit J; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Thomas MF; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Gerszten RE; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Heimberg GS; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Hoover PJ; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Lieb DJ; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Lin B; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Ngo D; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Pelka K; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Reyes M; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Smillie CS; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Waghray A; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Wood TE; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Zajac AS; Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Jennings LL; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Grundberg I; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Bhattacharyya RP; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Parry BA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Villani AC; Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Sade-Feldman M; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Hacohen N; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
  • Goldberg MB; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Cell Rep Med ; 2(5): 100287, 2021 05 18.
Article in English | MEDLINE | ID: covidwho-1683718
Semantic information from SemMedBD (by NLM)
1. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
2. Patients LOCATION_OF Plasma
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma
3. Patients LOCATION_OF Plasma Proteins
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma Proteins
4. Plasma Proteins ASSOCIATED_WITH COVID-19
Subject
Plasma Proteins
Predicate
ASSOCIATED_WITH
Object
COVID-19
5. Malaise PROCESS_OF Survivors
Subject
Malaise
Predicate
PROCESS_OF
Object
Survivors
6. ACE2 gene|ACE2 PART_OF Cells
Subject
ACE2 gene|ACE2
Predicate
PART_OF
Object
Cells
7. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
8. Patients LOCATION_OF Plasma
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma
9. Patients LOCATION_OF Plasma Proteins
Subject
Patients
Predicate
LOCATION_OF
Object
Plasma Proteins
10. Plasma Proteins ASSOCIATED_WITH COVID-19
Subject
Plasma Proteins
Predicate
ASSOCIATED_WITH
Object
COVID-19
11. Malaise PROCESS_OF Survivors
Subject
Malaise
Predicate
PROCESS_OF
Object
Survivors
12. ACE2 gene|ACE2 PART_OF Cells
Subject
ACE2 gene|ACE2
Predicate
PART_OF
Object
Cells
ABSTRACT
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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Risk factors Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100287

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Observational study / Risk factors Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100287