Evidence map›Paper›PMID 32597954›Full record

ArticleBlood2020

Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome.

Elizabeth A Middleton, Xue-Yan He, Frederik Denorme, Robert A Campbell, David Ng, Steven P Salvatore, Maria Mostyka, Amelia Baxter-Stoltzfus, Alain C Borczuk, Massimo Loda and 14 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04808895 (Multicenter Randomized, Double-blind, Placebo-controlled, Clinical Trial of Acetylsalicylic Acid in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients), which is not on this map. Cited by 993 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
993citing papers in PubMed, 2 pooled it
93.4field-weighted citation impact, top 1% 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.

NCT04808895 phase3unknown statusnot on this mapstarted 2021, after this paper: background citation

Multicenter Randomized, Double-blind, Placebo-controlled, Clinical Trial of Acetylsalicylic Acid in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients (Asperum)

TypeinterventionalSponsorAzienda Ospedaliera Universitaria Integrata VeronaRan2021 to 2021Enrolled204ConditionsCOVID-19, Thrombosis PulmonaryArmsAcetylsalicylic acid, Placebo
3 · Its place in the literature

Who cites it

993 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,499 citations in OpenAlex.

  1. Pooled it
  2. Neutrophil Extracellular Traps in Viral Infections.Pathogens (Basel, Switzerland) · 2025
    Pooled it
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933 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

24 authors at 4 institutions in 1 country.

Elizabeth A MiddletonMolecular Medicine Program and.
Xue-Yan HeCold Spring Harbor Laboratory, Cancer Center, Cold Spring Harbor, NY.
Frederik DenormeMolecular Medicine Program and.
Robert A CampbellMolecular Medicine Program and.
David NgCold Spring Harbor Laboratory, Cancer Center, Cold Spring Harbor, NY.
Steven P SalvatoreDepartment of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
Maria MostykaDepartment of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
Amelia Baxter-StoltzfusDepartment of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
Alain C BorczukDepartment of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
Massimo LodaDepartment of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
Mark J CodyMolecular Medicine Program and.
Bhanu Kanth ManneMolecular Medicine Program and.
Irina PortierMolecular Medicine Program and.
Estelle S HarrisDepartment of Internal Medicine, University of Utah, Salt Lake City, UT.
Aaron C PetreyMolecular Medicine Program and.
Ellen J BeswickDepartment of Internal Medicine, University of Utah, Salt Lake City, UT.
Aleah F CaulinPEEL Therapeutics, Inc, Salt Lake City, UT; and.
Anthony IovinoDepartment of Pediatrics and.
Lisa M AbegglenDepartment of Pediatrics and.
Andrew S WeyrichMolecular Medicine Program and.
Matthew T RondinaMolecular Medicine Program and.
Mikala EgebladCold Spring Harbor Laboratory, Cancer Center, Cold Spring Harbor, NY.
Joshua D SchiffmanMolecular Medicine Program and.
Christian Con YostMolecular Medicine Program and.
University of Utah · USNewYork–Presbyterian Hospital · USPEEL Therapeutics (United States) · USCold Spring Harbor Laboratory · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Translational Control of Megakaryocyte and Platelet Gene Expression in DiseaseR35HL145237 · NHLBI · UNIVERSITY OF UTAH · PI WEYRICH, ANDREW S · 2019 to 2025
$4.7M
NETs: Protection or Harm in Neonatal Inflammation and InfectionR01HD093826 · NICHD · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI CHRISTIAN CON YOST · 2018 to 2026
$2.6M
OPA1 an Estrogen-Mediated Modulator of Platelet HyperactivationR33HL141783 · NHLBI · UNIVERSITY OF IOWA · PI ABEL, E DALE, RONDINA, MATTHEW THOMAS · 2020 to 2022
$2.2M
Translational Control of Megakaryocyte and Platelet Function in SepsisR01HL142804 · NHLBI · UNIVERSITY OF UTAH · PI RONDINA, MATTHEW THOMAS · 2018 to 2021
$1.9M
OPA1 an Estrogen-Mediated Modulator of Platelet HyperactivationR61HL141783 · NHLBI · UNIVERSITY OF IOWA · PI ABEL, E DALE, WEYRICH, ANDREW S · 2018 to 2019
$1.5M
Platelet-hyaluronan interactions as regulators of inflammation and thrombosisR00HL135265 · NHLBI · UNIVERSITY OF UTAH · PI PETREY, AARON CHRISTOPHER · 2020 to 2022
$747k
Interferon-Induced Transmembrane Protein 3 (IFITM3) Regulates Thrombosis During Inflammation in AgingK01AG059892 · NIA · UNIVERSITY OF UTAH · PI CAMPBELL, ROBERT A · 2019 to 2022
$400k
Platelet-hyaluronan interactions as regulators of inflammation and thrombosis."K99HL135265 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PETREY, AARON CHRISTOPHER · 2017 to 2018
$280k
Platelet Reprogramming During InflammationI01CX001696 · VA · VA SALT LAKE CITY HEALTHCARE SYSTEM · PI Matthew Thomas Rondina · 2018 to 2026
–
CSRD VA I01 CX001696NCI NIH HHS P30 CA045508NHLBI NIH HHS K99 HL135265NHLBI NIH HHS R00 HL135265NHLBI NIH HHS R01 HL142804NHLBI NIH HHS R33 HL141783NHLBI NIH HHS R35 HL145237NHLBI NIH HHS R61 HL141783NIA NIH HHS K01 AG059892NICHD NIH HHS R01 HD093826
6 · The paper itself

Abstract

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support. Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis. We studied the connection between NETs and COVID-19 severity and progression. We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17). We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines. Three COVID-19 lung autopsies were examined for NETs and platelet involvement. We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma. We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma. Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome. Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340). Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration. Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF. Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.

Indexed as

AdultAgedBetacoronavirusBlood PlateletsBlood ProteinsCoronavirus InfectionsCOVID-19Extracellular TrapsFemaleHumansMaleMiddle AgedNeutrophil InfiltrationNeutrophilsPandemicsPeroxidaseBlood ProteinsnNIF peptide, humanPeroxidase

Identifiers

PMID32597954
PMCPMC7472714
OpenAlexW3037020655

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.