Evidence map›Paper›PMID 37147288›Full record

ArticleNature communications2023

Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation.

Yafeng Li, Jessica S Hook, Qing Ding, Xue Xiao, Stephen S Chung, Marcel Mettlen, Lin Xu, Jessica G Moreland, Michalis Agathocleous

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
6.6field-weighted citation impact, top 3% 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

30 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  4. Stem cell functionbioRxiv : the preprint server for biology · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Multi‑omics reveal neutrophil heterogeneity in sepsis (Review).International journal of molecular medicine · 2025
    Review
  10. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Yafeng LiChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jessica S HookDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-8344-8211
Qing DingChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Xue XiaoDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Stephen S ChungDepartment of Internal Medicine, Division of Hematology and Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Marcel MettlenDepartment of Cell Biology, Quantitative Light Microscopy Core, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lin XuDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-5815-4457
Jessica G MorelandDepartment of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0001-8487-9494
Michalis AgathocleousChildren's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA. michail.agathokleous@utsouthwestern.edu.ORCID 0000-0002-3427-1023
The University of Texas Southwestern Medical Center · USChildren's Medical Center · USSouthwestern Medical Center · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MELANIE H. COBB · 2010 to 2026
$53.7M
Mechanisms of telomere-induced disease: Role of intestinal malabsorption, barrier dysfunction and dsybiosis.R01DK127037 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI NOAH Freeman SHROYER, Ergun Sahin · 2022 to 2026
$3.3M
The role of ascorbate in myelopoiesis and infectionR01DK125713 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI AGATHOCLEOUS, MICHALIS · 2021 to 2025
$1.8M
The role of glycolysis and glucose oxidation in hematopoiesisR01HL161387 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI AGATHOCLEOUS, MICHALIS · 2022 to 2025
$1.6M
Spinning Disk Confocal for UT SouthwesternS10OD028630 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI LUBY-PHELPS, KATHERINE J · 2020 to 2020
$600k
Identifying neuroblastoma drivers and bringing them to the clinicR21CA259771 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI SKAPEK, STEPHEN X, XU, LIN · 2021 to 2021
$437k
NCI NIH HHS P30 CA142543NCI NIH HHS R21 CA259771NHLBI NIH HHS R01 HL161387NIDDK NIH HHS R01 DK125713NIDDK NIH HHS R01 DK127037NIH HHS S10 OD028630
6 · The paper itself

Abstract

Severe COVID-19 is characterized by an increase in the number and changes in the function of innate immune cells including neutrophils. However, it is not known how the metabolome of immune cells changes in patients with COVID-19. To address these questions, we analyzed the metabolome of neutrophils from patients with severe or mild COVID-19 and healthy controls. We identified widespread dysregulation of neutrophil metabolism with disease progression including in amino acid, redox, and central carbon metabolism. Metabolic changes in neutrophils from patients with severe COVID-19 were consistent with reduced activity of the glycolytic enzyme GAPDH. Inhibition of GAPDH blocked glycolysis and promoted pentose phosphate pathway activity but blunted the neutrophil respiratory burst. Inhibition of GAPDH was sufficient to cause neutrophil extracellular trap (NET) formation which required neutrophil elastase activity. GAPDH inhibition increased neutrophil pH, and blocking this increase prevented cell death and NET formation. These findings indicate that neutrophils in severe COVID-19 have an aberrant metabolism which can contribute to their dysfunction. Our work also shows that NET formation, a pathogenic feature of many inflammatory diseases, is actively suppressed in neutrophils by a cell-intrinsic mechanism controlled by GAPDH.

Indexed as

COVID-19Extracellular TrapsGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)HumansMetabolomeMetabolomicsNeutrophilsGAPDH protein, humanGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)

Identifiers

PMID37147288
PMCPMC10162006
OpenAlexW4372294691

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.