Evidence map›Paper›PMID 37559053›Full record

ArticleRespiratory research2023

Molecular mechanisms and treatment responses of pulmonary fibrosis in severe COVID-19.

Emma J Kooistra, Kilian Dahm, Antonius E van Herwaarden, Jelle Gerretsen, Melanie Nuesch Germano, Karoline Mauer, Ruben L Smeets, Sjef van der Velde, Maarten J W van den Berg, Johannes G van der Hoeven and 5 more

Open access · goldAbstract read
In one paragraph

Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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  3. Observational
  4. Article
  5. Article
  6. Review
  7. Article
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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

15 authors at 5 institutions in 2 countries.

Emma J KooistraDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
Kilian DahmTranslational Pediatrics, Department of Pediatrics, University Hospital Wuerzburg, 97080, Würzburg, Bavaria, Germany.
Antonius E van HerwaardenRadboudumc Laboratory for Diagnostics, Department of Laboratory Medicine, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
Jelle GerretsenDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
Melanie Nuesch GermanoLife and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Karoline MauerPRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany.
Ruben L SmeetsRadboudumc Laboratory for Diagnostics, Department of Laboratory Medicine, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.
Sjef van der VeldeDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
Maarten J W van den BergDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
Johannes G van der HoevenDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
Anna C AschenbrennerSystems Medicine, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany.
Joachim L SchultzePRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany.
Thomas UlasPRECISE Platform for Single Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, Germany.
Matthijs KoxDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands.
Peter PickkersDepartment of Intensive Care Medicine, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, The Netherlands. Peter.pickkers@radboudumc.nl.
Radboud University Nijmegen · NLRadboud University Medical Center · NLUniversity of Bonn · DEGerman Center for Neurodegenerative Diseases · DEEpigenomics (Germany) · DE

Funding

Radboudumc Coronavirus Disease 2019 grant (Radboudfonds)
6 · The paper itself

Abstract

backgroundCoronavirus disease 2019 (COVID-19) patients can develop pulmonary fibrosis (PF), which is associated with impaired outcome. We assessed specific leukocytic transcriptome profiles associated with PF and the influence of early dexamethasone (DEXA) treatment on the clinical course of PF in critically ill COVID-19 patients.

methodsWe performed a pre-post design study in 191 COVID-19 patients admitted to the Intensive Care Unit (ICU) spanning two treatment cohorts: the pre-DEXA- (n = 67) and the DEXA-cohort (n = 124). PF was identified based on radiological findings, worsening of ventilatory parameters and elevated circulating PIIINP levels. Longitudinal transcriptome profiles of 52 pre-DEXA patients were determined using RNA sequencing. Effects of prednisone treatment on clinical fibrosis parameters and outcomes were analyzed between PF- and no-PF-patients within both cohorts.

resultsTranscriptome analyses revealed upregulation of inflammatory, coagulation and neutrophil extracellular trap-related pathways in PF-patients compared to no-PF patients. Key genes involved included PADI4, PDE4D, MMP8, CRISP3, and BCL2L15. Enrichment of several identified pathways was associated with impaired survival in a external cohort of patients with idiopathic pulmonary fibrosis. Following prednisone treatment, PF-related profiles reverted towards those observed in the no-PF-group. Likewise, PIIINP levels decreased significantly following prednisone treatment. PF incidence was 28% and 25% in the pre-DEXA- and DEXA-cohort, respectively (p = 0.61). ICU length-of-stay (pre-DEXA: 42 [29-49] vs. 18 [13-27] days, p < 0.001; DEXA: 42 [28-57] vs. 13 [7-24] days, p < 0.001) and mortality (pre-DEXA: 47% vs. 15%, p = 0.009; DEXA: 61% vs. 19%, p < 0.001) were higher in the PF-groups compared to the no-PF-groups within both cohorts. Early dexamethasone therapy did not influence these outcomes.

conclusionsICU patients with COVID-19 who develop PF exhibit upregulated coagulation, inflammation, and neutrophil extracellular trap-related pathways as well as prolonged ICU length-of-stay and mortality. This study indicates that early dexamethasone treatment neither influences the incidence or clinical course of PF, nor clinical outcomes.

Indexed as

COVID-19Idiopathic Pulmonary FibrosisDexamethasoneDisease ProgressionHumansPrednisoneRespiration, ArtificialSARS-CoV-2DexamethasonePrednisoneAcute respiratory distress syndromeCoronavirus disease 2019DexamethasonePulmonary fibrosisTranscriptomics

Identifiers

PMID37559053
PMCPMC10413531
OpenAlexW4385704356

What OpenQuestion holds

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LicenceCC BY
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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.