ArticleIntensive care medicine experimental2023
Elevated free interleukin-18 associated with severity and mortality in prospective cohort study of 206 hospitalised COVID-19 patients.
Article in Intensive care medicine experimental, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
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- Diagnostic Usefulness of SP-D, CCL2/MCP-1, and IL-18 in Assessing Respiratory Function and Risk of Pulmonary Fibrosis in COVID-19 Patients.International journal of molecular sciences · 2026Article
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- Cytokine profiles, genetic polymorphisms, and systemic inflammatory markers in type 1 diabetes patients with COVID-19: IL-18 a predictor of disease severity.Frontiers in immunology · 2026Article
- Potential of biomarker-based enrichment strategies to identify critically ill patients for emerging cell death interventions.Cell death and differentiation · 2025Article
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- Identification of reactive CpGs and RNA expression in early COVID-19 through cis-eQTM analysis reflecting disease severity and recovery.Communications biology · 2025Article
- Profile of Cytokines Associated with SARS-CoV2 Seropositivity in Multiple Sclerosis Patients and Its Persistence over Six Months.Journal of clinical medicine · 2025Article
- Aging and inflammation limit the induction of SARS-CoV-2-specific CD8+ T cell responses in severe COVID-19.JCI insight · 2025Article
- IL-18 and IL-18BP: A Unique Dyad in Health and Disease.International journal of molecular sciences · 2024Review
- COVID-19 inflammatory signature in a Mozambican cohort: unchanged red blood series and reduced levels of IL-6 and other proinflammatory cytokines.BMC infectious diseases · 2024Article
- MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2.Molecular cancer · 2024Article
- Macrophage Activation Syndrome in Viral Sepsis.Viruses · 2024Review
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- An antibody to IL-1 receptor 7 protects mice from LPS-induced tissue and systemic inflammation.Frontiers in immunology · 2024Article
- Altered Ex Vivo NLRP3 Inflammasome Activation Is Associated with 28-Day Mortality in Septic Patients.Viruses · 2023Article
- COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.Medicina (Kaunas, Lithuania) · 2023Review
- Article
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDivergence between deterioration to life-threatening COVID-19 or clinical improvement occurs for most within the first 14 days of symptoms. Life-threatening COVID-19 shares clinical similarities with Macrophage Activation Syndrome, which can be driven by elevated Free Interleukin-18 (IL-18) due to failure of negative-feedback release of IL-18 binding protein (IL-18bp). We, therefore, designed a prospective, longitudinal cohort study to examine IL-18 negative-feedback control in relation to COVID-19 severity and mortality from symptom day 15 onwards.
methods662 blood samples, matched to time from symptom onset, from 206 COVID-19 patients were analysed by enzyme-linked immunosorbent assay for IL-18 and IL-18bp, enabling calculation of free IL-18 (fIL-18) using the updated dissociation constant (K
resultsRange of fIL-18 in COVID-19 cohort was 10.05-1157.7 pg/ml. Up to symptom day 14, mean fIL-18 levels increased in all patients. Levels in survivors declined thereafter, but remained elevated in non-survivors. Adjusted regression analysis from symptom day 15 onwards showed a 100 mmHg decrease in PaO
conclusionsElevated free IL-18 levels from symptom day 15 onwards are associated with COVID-19 severity and mortality. ISRCTN: #13450549; registration date: 30/12/2020.
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