Evidence map›Paper›PMID 34386774›Full record

ArticleCritical care explorations2021

Defining Potential Therapeutic Targets in Coronavirus Disease 2019: A Cross-Sectional Analysis of a Single-Center Cohort.

Nishkantha Arulkumaran, Timothy Arthur Chandos Snow, Adarsh Kulkarni, David Brealey, Hannah Rickman, Chloe Rees-Spear, Moira J Spyer, Judith Heaney, Edmund Garr, Bryan Williams and 7 more

Abstract read
In one paragraph

Article in Critical care explorations, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
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

17 authors.

Nishkantha ArulkumaranBloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
Timothy Arthur Chandos SnowBloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
Adarsh KulkarniBloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
David BrealeyBloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
Hannah RickmanDepartment of Clinical Virology, University College London Hospital, London, United Kingdom.
Chloe Rees-SpearDivision of Infection and Immunity, University College London, London, United Kingdom.
Moira J SpyerDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
Judith HeaneyAdvanced Pathogen Diagnostics Unit, Department of Clinical Virology, University College London Hospitals NHS Trust, London, United Kingdom.
Edmund GarrNIHR University College London Hospitals (UCL) Biomedical Research Centre, London, United Kingdom.
Bryan WilliamsNeuroimmunology and CSF Laboratory, University College London Hospitals, National Hospital of Neurology and Neurosurgery, London, United Kingdom.
Peter CherepanovChromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, United Kingdom.
George KassiotisRetroviral Immunology Laboratory, The Francis Crick Institute, London, United Kingdom.
Michael LunnNeuroimmunology and CSF Laboratory, University College London Hospitals, National Hospital of Neurology and Neurosurgery, London, United Kingdom.
Catherine HoulihanDepartment of Clinical Virology, University College London Hospital, London, United Kingdom.
Laura E McCoyDivision of Infection and Immunity, University College London, London, United Kingdom.
Eleni NastouliDepartment of Clinical Virology, University College London Hospital, London, United Kingdom.
Mervyn SingerBloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.

Funding

Medical Research Council MR/R008698/1
6 · The paper itself

Abstract

objectivesMultiple mechanisms have been proposed to explain disease severity in coronavirus disease 2019. Therapeutic approaches need to be underpinned by sound biological rationale. We evaluated whether serum levels of a range of proposed coronavirus disease 2019 therapeutic targets discriminated between patients with mild or severe disease.

designA search of ClinicalTrials.gov identified coronavirus disease 2019 immunological drug targets. We subsequently conducted a retrospective observational cohort study investigating the association of serum biomarkers within the first 5 days of hospital admission relating to putative therapeutic biomarkers with illness severity and outcome.

settingUniversity College London, a tertiary academic medical center in the United Kingdom. PATIENTS: Patients admitted to hospital with a diagnosis of coronavirus disease 2019.

interventionsNone. MEASUREMENTS AND MAIN

resultsEighty-six patients were recruited, 44 (51%) with mild disease and 42 (49%) with severe disease. We measured levels of 10 cytokines/signaling proteins related to the most common therapeutic targets (granulocyte-macrophage colony-stimulating factor, interferon-α2a, interferon-β, interferon-γ, interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, interleukin-7, interleukin-8, tumor necrosis factor-α), immunoglobulin G antibodies directed against either coronavirus disease 2019 spike protein or nucleocapsid protein, and neutralization titers of antibodies. Four-hundred seventy-seven randomized trials, including 168 different therapies against 83 different pathways, were identified. Six of the 10 markers (interleukin-6, interleukin-7, interleukin-8, interferon-α2a, interferon-β, interleukin-1 receptor antagonist) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable spike protein or nucleocapsid protein immunoglobulin G antibodies with equivalent levels between groups. Neutralization titers were higher among patients with severe disease.

conclusionsSome therapeutic and prognostic biomarkers may be useful in identifying coronavirus disease 2019 patients who may benefit from specific immunomodulatory therapies, particularly interleukin-6. However, biomarker absolute values often did not discriminate between patients with mild and severe disease or death, implying that these immunomodulatory treatments may be of limited benefit.

Indexed as

acute respiratory distress syndromecoronavirus disease 2019critical carecytokineimmunomodulationinterleukin-6

Identifiers

PMID34386774
PMCPMC8352605

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LicenceCC BY-NC-ND
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Registered trials

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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.