In:
Intensive Care Medicine Experimental, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2023-02-24)
Kurzfassung:
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 (K d ) 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 PaO 2 /FiO 2 (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). Conclusions Elevated free IL-18 levels from symptom day 15 onwards are associated with COVID-19 severity and mortality. ISRCTN: #13450549; registration date: 30/12/2020.
Materialart:
Online-Ressource
ISSN:
2197-425X
DOI:
10.1186/s40635-022-00488-x
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2023
ZDB Id:
2740385-3
