Evidence map›Paper›PMID 34991159›Full record

ArticleBlood advances2022

Inflammasome activation in neutrophils of patients with severe COVID-19.

Karen Aymonnier, Julie Ng, Laura E Fredenburgh, Katherin Zambrano-Vera, Patrick Münzer, Sarah Gutch, Shoichi Fukui, Michael Desjardins, Meera Subramaniam, Rebecca M Baron and 4 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

62 citing papers in PubMed, 89 citations in OpenAlex.

  1. Review
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    Review
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2 more citing papers are in PubMed but not listed here.

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

14 authors at 3 institutions in 3 countries.

Karen AymonnierProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.ORCID 0000-0002-9587-8822
Julie NgDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0003-0490-208X
Laura E FredenburghDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0002-7447-6453
Katherin Zambrano-VeraDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0003-1310-4901
Patrick MünzerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.
Sarah GutchProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.ORCID 0000-0002-2615-8266
Shoichi FukuiProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.
Michael DesjardinsDepartment of Medicine, Brigham and Women's Hospital, Boston, MA.ORCID 0000-0003-4028-8507
Meera SubramaniamDivision of Pulmonary Medicine, and.
Rebecca M BaronDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Benjamin A RabyDivision of Pulmonary Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA.ORCID 0000-0003-2206-5748
Mark A PerrellaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
James A LedererDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; and.
Denisa D WagnerProgram in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA.ORCID 0000-0002-4494-413X
Brigham and Women's Hospital · USBoston Children's Hospital · USPulmonary Associates · US

Funding

RESPIRATORY RESEARCHT32HL007633 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI George R Washko · 1985 to 2026
$14.9M
How inflammation and thrombosis fuel disease and aging: Focus on NETsR35HL135765 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WAGNER, DENISA D · 2017 to 2023
$6.2M
Therapy of acute radiation syndrome and its complications by mesenchymal stromal cells conditioned with Toll-like receptor 9 agonistsU01AI138318 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI LEDERER, JAMES A., PERRELLA, MARK A · 2018 to 2022
$3.1M
NHLBI NIH HHS R35 HL135765NHLBI NIH HHS T32 HL007633NIAID NIH HHS U01 AI138318
6 · The paper itself

Abstract

Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the inflammasome in monocytes and macrophages and leads to the cytokine storm in COVID-19. Neutrophils, the most abundant leukocytes, release neutrophil extracellular traps (NETs), which have been implicated in the pathogenesis of COVID-19. Our recent study shows that activation of the NLRP3 inflammasome is important for NET release in sterile inflammation. However, the role of neutrophil inflammasome formation in human disease is unknown. We hypothesized that SARS-CoV-2 infection may induce inflammasome activation in neutrophils. We also aimed to assess the localization of inflammasome formation (ie, apoptosis-associated speck-like protein containing a CARD [ASC] speck assembly) and timing relative to NETosis in stimulated neutrophils by real-time video microscopy. Neutrophils isolated from severe COVID-19 patients demonstrated that ∼2% of neutrophils in both the peripheral blood and tracheal aspirates presented ASC speck. ASC speck was observed in neutrophils with an intact poly-lobulated nucleus, suggesting early formation during neutrophil activation. Additionally, 40% of nuclei were positive for citrullinated histone H3, and there was a significant correlation between speck formation and nuclear histone citrullination. Time-lapse microscopy in lipopolysaccharide -stimulated neutrophils from fluorescent ASC reporter mice showed that ASC speck formed transiently and at the microtubule organizing center long before NET release. Our study shows that ASC speck is present in neutrophils from COVID-19 patients with respiratory failure and that it forms early in NETosis. Our findings suggest that inhibition of neutrophil inflammasomes may be beneficial in COVID-19.

Indexed as

COVID-19Extracellular TrapsAnimalsHumansInflammasomesMiceNeutrophilsSARS-CoV-2Inflammasomes

Identifiers

PMID34991159
PMCPMC8741335
OpenAlexW4205235414

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.