Evidence map›Paper›PMID 33969320›Full record

ArticleCell reports. Medicine2021

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 and 33 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
182citing papers in PubMed, 1 pooled it
17.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

182 citing papers in PubMed, 1 synthesis or guideline pooled it, 302 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Secreted phospholipase PLA2G5 acts as a hemolytic factor in sepsis.The Journal of clinical investigation · 2026
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Proteomic Analysis of COVID-19 Infection.Advances in experimental medicine and biology · 2026
    Article
  18. Article
  19. Multi-omics Data Integration.Advances in experimental medicine and biology · 2026
    Review
  20. Article

122 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors at 11 institutions in 2 countries.

Michael R FilbinDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Arnav MehtaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Alexis M SchneiderBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Kyle R KaysDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Jamey R GuessOlink Proteomics, Watertown, MA, USA.
Matteo GentiliBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Bánk G FenyvesDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Nicole C CharlandDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Anna L K GonyeBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Irena GushterovaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Hargun K KhannaDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Thomas J LaSalleBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Kendall M Lavin-ParsonsDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Brendan M LilleyDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Carl L LodensteinDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Kasidet ManakongtreecheepBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Justin D MargolinDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Brenna N McKaigDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Maricarmen Rojas-LopezDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Brian C RussoDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Nihaarika SharmaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Jessica TantivitBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Molly F ThomasBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Robert E GersztenDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Graham S HeimbergBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Paul J HooverDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
David J LiebBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Brian LinDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Debby NgoDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Karin PelkaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Miguel ReyesBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Christopher S SmillieBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Avinash WaghrayDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Thomas E WoodDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Amanda S ZajacDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Lori L JenningsNovartis Institutes for BioMedical Research, Cambridge, MA, USA.
Ida GrundbergOlink Proteomics, Watertown, MA, USA.
Roby P BhattacharyyaBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Blair Alden ParryDepartment of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
Alexandra-Chloé VillaniBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Moshe Sade-FeldmanBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Nir HacohenBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Marcia B GoldbergBroad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, USA.
Massachusetts General Hospital · USBroad Institute · USHarvard University · USMassachusetts Institute of Technology · USBeth Israel Deaconess Medical Center · USCenter for Cancer Research · USOlink (United States) · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USNovartis (United States) · USSemmelweis University · HU

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Virology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI GEORG Michael LAUER · 2009 to 2026
$48.1M
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
INFECTIOUS DISEASE AND BASIC MICROBIOLOGICAL MECHANISMST32AI007061 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Marcia B Goldberg · 1985 to 2026
$12.1M
Training Program in Cancer Biology and TherapeuticsT32CA071345 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber, Lecia V. Sequist · 1997 to 2026
$10.6M
NCATS NIH HHS UL1 TR001102NCATS NIH HHS UL1 TR002541NCI NIH HHS T32 CA071345NIAID NIH HHS T32 AI007061NIAID NIH HHS U19 AI082630NIDDK NIH HHS P30 DK043351
6 · The paper itself

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.

Indexed as

acute respiratory distress syndromeARDSCOVID-19 severitydeath versus survivalintracellular death signatureslongitudinallung epithelial cellslung monocyte/macrophagespancreatic exocrine proteasesplasma proteomicsT cell activation

Identifiers

PMID33969320
PMCPMC8091031
OpenAlexW3159431441

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.