Evidence map›Paper›PMID 34956213›Full record

ArticleFrontiers in immunology2021

Extracellular Vesicle Associated miRNAs Regulate Signaling Pathways Involved in COVID-19 Pneumonia and the Progression to Severe Acute Respiratory Corona Virus-2 Syndrome.

Agnes S Meidert, Stefanie Hermann, Florian Brandes, Benedikt Kirchner, Dominik Buschmann, Jean-Noël Billaud, Matthias Klein, Anja Lindemann, Elisa Aue, Gustav Schelling and 2 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.

  1. Pooled it
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  14. Extracellular Vesicles: The Invisible Heroes and Villains of COVID-19 Central Neuropathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
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  19. Extracellular Vesicles and Their Role in Lung Infections.International journal of molecular sciences · 2023
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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

12 authors at 3 institutions in 1 country.

Agnes S MeidertDepartment of Anesthesiology, University Hospital, LMU, Munich, Germany.
Stefanie HermannDivision of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Florian BrandesDepartment of Anesthesiology, University Hospital, LMU, Munich, Germany.
Benedikt KirchnerDivision of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Dominik BuschmannDepartment of Anesthesiology, University Hospital, LMU, Munich, Germany.
Jean-Noël BillaudQIAGEN Digital Insights, Redwood City, CA, United States.
Matthias KleinDepartment of Neurology, University Hospital, LMU, Munich, Germany.
Anja LindemannInstitute of Human Genetics, University Hospital, LMU, Munich, Germany.
Elisa AueDepartment of Anesthesiology, University Hospital, LMU, Munich, Germany.
Gustav SchellingDepartment of Anesthesiology, University Hospital, LMU, Munich, Germany.
Michael W PfafflDivision of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Marlene ReithmairInstitute of Human Genetics, University Hospital, LMU, Munich, Germany.
LMU Klinikum · DELudwig-Maximilians-Universität München · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Extracellular vesicles (EVs) are mediators of cell-to-cell communication in inflammatory lung diseases. They function as carriers for miRNAs which regulate mRNA transcripts and signaling pathways after uptake into recipient cells. We investigated whether miRNAs associated with circulating EVs regulate immunologic processes in COVID-19. Methods: We prospectively studied 20 symptomatic patients with COVID-19 pneumonia, 20 mechanically ventilated patients with severe COVID-19 (severe acute respiratory corona virus-2 syndrome, ARDS) and 20 healthy controls. EVs were isolated by precipitation, total RNA was extracted, profiled by small RNA sequencing and evaluated by differential gene expression analysis (DGE). Differentially regulated miRNAs between groups were bioinformatically analyzed, mRNA target transcripts identified and signaling networks constructed, thereby comparing COVID-19 pneumonia to the healthy state and pneumonia to severe COVID-19 ARDS. Results: DGE revealed 43 significantly and differentially expressed miRNAs (25 downregulated) in COVID-19 pneumonia when compared to controls, and 20 miRNAs (15 downregulated) in COVID-19 ARDS patients in comparison to those with COVID-19 pneumonia. Network analysis for comparison of COVID-19 pneumonia to healthy controls showed upregulated miR-3168 (log2FC=2.28, p Conclusion: EV-derived miRNAs might have important regulative functions in the pathophysiology of COVID-19: CXCL8 regulates neutrophil recruitment into the lung causing epithelial damage whereas activated TLR4, to which SARS-CoV-2 spike protein binds strongly, increases cell surface ACE2 expression and destroys type II alveolar cells that secrete pulmonary surfactants; both resulting in pulmonary-capillary leakage and ARDS. These miRNAs may serve as biomarkers or as possible therapeutic targets.

Indexed as

AgedAged, 80 and overBiomarkersCOVID-19Disease ProgressionExtracellular VesiclesFemaleHumansMaleMicroRNAsMiddle AgedPneumoniaSARS-CoV-2Signal TransductionBiomarkersMicroRNAsARDScell-free microRNAscommunity acquired pneumoniaCOVID-19extracellular vesiclessepsisSevere Acute Respiratory Corona Virus-2 Syndromesmall RNA sequencing

Identifiers

PMID34956213
PMCPMC8696174
OpenAlexW4200120351

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.