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Defining Potential Therapeutic Targets in Coronavirus Disease 2019: A Cross-Sectional Analysis of a Single-Center Cohort
- Source :
- Critical Care Explorations, Vol 3, Iss 8, p e0488 (2021), Critical Care Explorations
- Publication Year :
- 2021
- Publisher :
- Wolters Kluwer, 2021.
-
Abstract
- Supplemental Digital Content is available in the text.<br />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-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. 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.
- Subjects :
- medicine.medical_specialty
Cross-sectional study
Observational Study
immunomodulation
Immunoglobulin G
law.invention
coronavirus disease 2019
Randomized controlled trial
law
Internal medicine
cytokine
Medicine
Interleukin 6
biology
business.industry
RC86-88.9
interleukin-6
Medical emergencies. Critical care. Intensive care. First aid
General Medicine
acute respiratory distress syndrome
critical care
Cohort
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
biology.protein
Biomarker (medicine)
Antibody
business
Cohort study
Subjects
Details
- Language :
- English
- ISSN :
- 26398028
- Volume :
- 3
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Critical Care Explorations
- Accession number :
- edsair.doi.dedup.....431bb8248429a7880be4914c7d22d9af