Evidence map›Paper›PMID 34981052›Full record

ArticlebioRxiv : the preprint server for biology2021

Neutrophil Profiles of Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children.

Brittany P Boribong, Thomas J LaSalle, Yannic C Bartsch, Felix Ellett, Maggie E Loiselle, Jameson P Davis, Anna L K Gonye, Soroush Hajizadeh, Johannes Kreuzer, Shiv Pillai and 7 more

Open access · greenAbstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 19 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Brittany P BoribongMucosal Immunology and Biology Research Center, Massachusetts General Hospital; Boston, USA.
Thomas J LaSalleCenter for Cancer Research, Department of Medicine, Massachusetts General Hospital; Boston, USA.
Yannic C BartschDepartment of Medicine, Harvard Medical School; Boston, USA.
Felix EllettBioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School; Boston, USA.
Maggie E LoiselleMucosal Immunology and Biology Research Center, Massachusetts General Hospital; Boston, USA.
Jameson P DavisMucosal Immunology and Biology Research Center, Massachusetts General Hospital; Boston, USA.
Anna L K GonyeCenter for Cancer Research, Department of Medicine, Massachusetts General Hospital; Boston, USA.
Soroush HajizadehDepartment of Medicine, Harvard Medical School; Boston, USA.
Johannes KreuzerDepartment of Medicine, Harvard Medical School; Boston, USA.
Shiv PillaiDepartment of Medicine, Harvard Medical School; Boston, USA.
Wilhelm HaasDepartment of Medicine, Harvard Medical School; Boston, USA.
Andrea EdlowDepartment of Medicine, Harvard Medical School; Boston, USA.
Alessio FasanoMucosal Immunology and Biology Research Center, Massachusetts General Hospital; Boston, USA.
Galit AlterDepartment of Medicine, Harvard Medical School; Boston, USA.
Daniel IrimiaBioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School; Boston, USA.
Moshe Sade-FeldmanDepartment of Medicine, Harvard Medical School; Boston, USA.
Lael M YonkerMucosal Immunology and Biology Research Center, Massachusetts General Hospital; Boston, USA.
Harvard University · USBroad Institute · USMassachusetts General Hospital · USShriners Hospitals for Children - Erie · US

Funding

Mechanistically Disentangling the Infected, Inflamed LungK08HL143183 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI YONKER, LAEL · 2018 to 2022
$869k
NHLBI NIH HHS K08 HL143183
6 · The paper itself

Abstract

Multisystem Inflammatory Syndrome in Children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory systemic illness characterized by SARS-CoV-2 antigenemia, cytokine storm and immune dysregulation; however, the role of the neutrophil has yet to be defined. In adults with severe COVID-19, neutrophil activation has been shown to be central to overactive inflammatory responses and complications. Thus, we sought to define neutrophil activation in children with MIS-C and acute COVID-19. We collected samples from 141 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 67 pediatric controls. We found that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism, which is markedly different than the neutrophil interferon-stimulated gene (ISG) response observed in pediatric patients during acute SARS-CoV-2 infection. Moreover, we identified signatures of neutrophil activation and degranulation with high levels of spontaneous neutrophil extracellular trap (NET) formation in neutrophils isolated from fresh whole blood of MIS-C patients. Mechanistically, we determined that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Overall, our findings suggest that the hyperinflammatory presentation of MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia through uncontrolled neutrophil activation and NET release in the vasculature. ONE SENTENCE SUMMARY: Circulating SARS-CoV-2 antigen:antibody immune complexes in Multisystem Inflammatory Syndrome in Children (MIS-C) drive hyperinflammatory and coagulopathic neutrophil extracellular trap (NET) formation and neutrophil activation pathways, providing insight into disease pathology and establishing a divergence from neutrophil signaling seen in acute pediatric COVID-19.

Identifiers

PMID34981052
PMCPMC8722589
OpenAlexW4200193382

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.