@article{Nasser:2023:10.1186/s40635-022-00488-x,
author = {Nasser, SMT and Rana, AA and Doffinger, R and Kafizas, A and Khan, TA and Nasser, S},
doi = {10.1186/s40635-022-00488-x},
journal = {Intensive Care Medicine Experimental},
title = {Elevated free interleukin-18 associated with severity and mortality in prospective cohort study of 206 hospitalised COVID-19 patients},
url = {http://dx.doi.org/10.1186/s40635-022-00488-x},
volume = {11},
year = {2023}
}

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TY  - JOUR
AB  - 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 (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.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 PaO2/FiO2 (primary outcome) for each 37.7 pg/ml increase in highest fIL-18 (p < 0.03). Per 50 pg/ml increase in highest fIL-18, adjusted logistic regression gave an odds-ratio (OR) for crude 60-day mortality of 1.41 (1.1–2.0) (p < 0.03), and an OR for death with hypoxaemic respiratory failure of 1.90 [1.3–3.1] (p < 0.01). Highest fIL-18 was associated also with organ failure in patients with hypoxaemic respiratory failure, with an increase of 63.67 pg/ml for every additional organ supported (p < 0.01).ConclusionsElevated free IL-
AU  - Nasser,SMT
AU  - Rana,AA
AU  - Doffinger,R
AU  - Kafizas,A
AU  - Khan,TA
AU  - Nasser,S
DO  - 10.1186/s40635-022-00488-x
PY  - 2023///
SN  - 2197-425X
TI  - Elevated free interleukin-18 associated with severity and mortality in prospective cohort study of 206 hospitalised COVID-19 patients
T2  - Intensive Care Medicine Experimental
UR  - http://dx.doi.org/10.1186/s40635-022-00488-x
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000937710000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://icm-experimental.springeropen.com/articles/10.1186/s40635-022-00488-x
UR  - http://hdl.handle.net/10044/1/107839
VL  - 11
ER  - 

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