Evidence map›Paper›PMID 33619472›Full record

ArticleResearch square2021

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 Mazer, Annie Hess, Jennifer Leonard and 3 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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 TurnbullDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Anja FuchsDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Kenneth E RemyDepartment of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Michael P KellyDepartment of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Elfaridah P FrazierDepartment of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Sarbani GhoshDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Shin-Wen ChangDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Monty MazerDepartment of Anesthesia, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Annie HessDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Jennifer LeonardDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Mark HoofnagleDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Marco ColonnaDepartment of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Richard S HotchkissDepartment of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Washington University in St. Louis · US

Funding

WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
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
Impact of Red Blood Cell (RBC)-Derived DAMPs on Host Immune Response in Pediatric SepsisK08GM129763 · NIGMS · WASHINGTON UNIVERSITY · PI REMY, KENNETH EUGENE · 2018 to 2021
$714k
NCATS NIH HHS UL1 TR002345NIGMS NIH HHS K08 GM129763NIGMS 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 450,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated local 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. 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 and was tightly correlated with circulating IL-6 levels. High levels of STAT3 phosphorylation was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-gamma 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.

Identifiers

PMID33619472
PMCPMC7899466
OpenAlexW3130908167

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.