Evidence map›Paper›PMID 39052740›Full record

ArticleThe Journal of infectious diseases2024

Delayed Mucosal Antiviral Responses Despite Robust Peripheral Inflammation in Fatal COVID-19.

Jasmin K Sidhu, Matthew K Siggins, Felicity Liew, Clark D Russell, Ashley S S Uruchurtu, Christopher Davis, Lance Turtle, Shona C Moore, Hayley E Hardwick, Wilna Oosthuyzen and 6 more

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
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

16 authors.

Jasmin K SidhuNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Matthew K SigginsNational Heart and Lung Institute, Imperial College London, London, United Kingdom.ORCID 0000-0003-2504-6518
Felicity LiewNational Heart and Lung Institute, Imperial College London, London, United Kingdom.ORCID 0000-0002-8736-9198
Clark D RussellCentre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
Ashley S S UruchurtuNational Heart and Lung Institute, Imperial College London, London, United Kingdom.
Christopher DavisMedical Research Council Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.
Lance TurtleDepartment of Clinical Infection, Microbiology, and Immunology, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0002-0778-1693
Shona C MooreDepartment of Clinical Infection, Microbiology, and Immunology, University of Liverpool, Liverpool, United Kingdom.
Hayley E HardwickDepartment of Clinical Infection, Microbiology, and Immunology, University of Liverpool, Liverpool, United Kingdom.
Wilna OosthuyzenRoslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
Emma C ThomsonMedical Research Council Centre for Virus Research, University of Glasgow, Glasgow, United Kingdom.ORCID 0000-0003-1482-0889
Malcolm G SempleNational Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary, and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.ORCID 0000-0001-9700-0418
J Kenneth BaillieRoslin Institute, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0001-5258-793X
Peter J M OpenshawNational Heart and Lung Institute, Imperial College London, London, United Kingdom.ORCID 0000-0002-7220-2555
Ryan S ThwaitesNational Heart and Lung Institute, Imperial College London, London, United Kingdom.ORCID 0000-0003-3052-2793
ISARIC4C investigators

Funding

Bill and Melinda Gates Foundation OPP1209135Department for International Development 215091/Z/18/ZImperial College LondonLiverpool Experimental Cancer Medicine Centre C18616/A25153Medical Research Council MC_PC_19059MRC MR/W000970/1National Institute for Health Research CO-CIN-01NIHR 200907Public Health EnglandUK Coronavirus Immunology ConsortiumU.S. Food and Drug Administration 75F40120C00085Wellcome Trust 205228/Z/16/Z
6 · The paper itself

Abstract

backgroundWhile inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation.

methodsWe measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days after symptom onset) or late (6-20 days after symptom onset) phase.

resultsPatients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease.

conclusionsDefective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19.

Indexed as

COVID-19CytokinesInflammationSARS-CoV-2AdultAgedChemokinesFemaleHumansImmunity, MucosalMaleMiddle AgedNasal MucosaSeverity of Illness IndexViral LoadChemokinesCytokinesairwaychemokineCOVID-19cytokinelungmucosanoseSARS-CoV-2virus

Identifiers

PMID39052740
PMCPMC11272059

What OpenQuestion holds

Textmetadata
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.