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Defining Potential Therapeutic Targets in Coronavirus Disease 2019: A Cross-Sectional Analysis of a Single-Center Cohort.
Arulkumaran, Nishkantha; Snow, Timothy Arthur Chandos; Kulkarni, Adarsh; Brealey, David; Rickman, Hannah; Rees-Spear, Chloe; Spyer, Moira J; Heaney, Judith; Garr, Edmund; Williams, Bryan; Cherepanov, Peter; Kassiotis, George; Lunn, Michael; Houlihan, Catherine; McCoy, Laura E; Nastouli, Eleni; Singer, Mervyn.
  • Arulkumaran N; Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
  • Snow TAC; Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
  • Kulkarni A; Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
  • Brealey D; Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
  • Rickman H; Department of Clinical Virology, University College London Hospital, London, United Kingdom.
  • Rees-Spear C; Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
  • Spyer MJ; Division of Infection and Immunity, University College London, London, United Kingdom.
  • Heaney J; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
  • Garr E; Advanced Pathogen Diagnostics Unit, Department of Clinical Virology, University College London Hospitals NHS Trust, London, United Kingdom.
  • Williams B; Advanced Pathogen Diagnostics Unit, Department of Clinical Virology, University College London Hospitals NHS Trust, London, United Kingdom.
  • Cherepanov P; NIHR University College London Hospitals (UCL) Biomedical Research Centre, London, United Kingdom.
  • Kassiotis G; Neuroimmunology and CSF Laboratory, University College London Hospitals, National Hospital of Neurology and Neurosurgery, London, United Kingdom.
  • Lunn M; Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute, London, United Kingdom.
  • Houlihan C; Retroviral Immunology Laboratory, The Francis Crick Institute, London, United Kingdom.
  • McCoy LE; Neuroimmunology and CSF Laboratory, University College London Hospitals, National Hospital of Neurology and Neurosurgery, London, United Kingdom.
  • Nastouli E; Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
  • Singer M; Department of Clinical Virology, University College London Hospital, London, United Kingdom.
Crit Care Explor ; 3(8): e0488, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1356719
ABSTRACT

OBJECTIVES:

Multiple 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.

DESIGN:

A 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.

SETTING:

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

INTERVENTIONS:

None. MEASUREMENTS AND MAIN

RESULTS:

Eighty-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-ß, interferon-γ, interleukin-1ß, 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-ß, 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.

CONCLUSIONS:

Some 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.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Controlled clinical trial / Observational study / Prevalence study / Prognostic study / Randomized controlled trials / Risk factors Language: English Journal: Crit Care Explor Year: 2021 Document Type: Article Affiliation country: CCE.0000000000000488

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Controlled clinical trial / Observational study / Prevalence study / Prognostic study / Randomized controlled trials / Risk factors Language: English Journal: Crit Care Explor Year: 2021 Document Type: Article Affiliation country: CCE.0000000000000488