Elevated free interleukin-18 associated with severity and mortality in prospective cohort study of 206 hospitalised COVID-19 patients

Autor: Syed M. T. Nasser, Anas A. Rana, Rainer Doffinger, Andreas Kafizas, Tauseef A. Khan, Shuaib Nasser
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Intensive Care Medicine Experimental, Vol 11, Iss 1, Pp 1-19 (2023)
Druh dokumentu: article
ISSN: 2197-425X
DOI: 10.1186/s40635-022-00488-x
Popis: Abstract Background Divergence 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. Methods 662 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 (Kd) of 0.05 nmol. Adjusted multivariate regression analysis was used to assess the relationship between highest fIL-18 and outcome measures of COVID-19 severity and mortality. Re-calculated fIL-18 values from a previously studied healthy cohort are also presented. Results Range 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 PaO2/FiO2 (primary outcome) for each 37.7 pg/ml increase in highest fIL-18 (p
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