Evidence map›Paper›PMID 35421120›Full record

ArticlePloS one2022

Dysregulation of the leukocyte signaling landscape during acute COVID-19.

Isaiah R Turnbull, Anja Fuchs, Kenneth E Remy, Michael P Kelly, Elfaridah P Frazier, Sarbani Ghosh, Shin-Wen Chang, Monty B Mazer, Annie Hess, Jennifer M Leonard and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 26% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. COVID-19 disease and immune dysregulation.Best practice & research. Clinical haematology · 2022
    Review
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Isaiah R TurnbullDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-1437-8480
Anja FuchsDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Kenneth E RemyDepartments of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Michael P KellyDepartments of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-6221-7406
Elfaridah P FrazierDepartments of Orthopedic Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Sarbani GhoshDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Shin-Wen ChangDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Monty B MazerDepartments of Anesthesia, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-4159-8585
Annie HessDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Jennifer M LeonardDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Mark H HoofnagleDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-6080-5244
Marco ColonnaDepartments of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Richard S HotchkissDepartments of Surgery, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Washington University in St. Louis · US

Funding

Enhancing Innate and Adaptive Immunity to Improve Sepsis SurvivalR35GM126928 · NIGMS · WASHINGTON UNIVERSITY · PI Richard Samuel Hotchkiss · 2018 to 2026
$4.7M
Hematopoietic Stem and Progenitor Cell Dysfunction is an Underlying Mechanism of Injury-Inuced ImmunosuppressionR35GM133756 · NIGMS · WASHINGTON UNIVERSITY · PI TURNBULL, ISAIAH R · 2019 to 2023
$2.0M
Netosis in Trauma Mediated Acute Lung InjuryK08GM137323 · NIGMS · WASHINGTON UNIVERSITY · PI LEONARD, JENNIFER · 2021 to 2024
$721k
NHLBI NIH HHS L70 HL165646NIGMS NIH HHS K08 GM137323NIGMS NIH HHS R35 GM126928NIGMS NIH HHS R35 GM133756
6 · The paper itself

Abstract

The global COVID-19 pandemic has claimed the lives of more than 750,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. We find that although COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations, STAT3 phosphorylation predominated in both monocytes and T cells. STAT3 phosphorylation was tightly correlated with circulating IL-6 levels and high levels of phospho-STAT3 was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-γ production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19.

Indexed as

COVID-19HumansMonocytesPandemicsSignal TransductionSTAT3 Transcription FactorT-LymphocytesSTAT3 Transcription Factor

Identifiers

PMID35421120
PMCPMC9009616
OpenAlexW4225782389

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.