Inflammasome Axis Analysis in COVID-19 (ISAAC)
Research type
Research Study
Full title
Levels of Free IL-18, IL-18 Binding Protein and Granzyme B according to disease severity of COVID-19
IRAS ID
285842
Contact name
Syed Muhammad Tahir Nasser
Contact email
Sponsor organisation
Surrey and Sussex Healthcare NHS Trust
ISRCTN Number
ISRCTN13450549
Duration of Study in the UK
0 years, 5 months, 28 days
Research summary
Interleukin-18 (IL-18) plays a fundamental role in the viral-mediated inflammatory process. It is produced as the end-product of what is known as “Inflammasome” activation, a process that occurs with viral or bacterial pathogen detection or cellular damage. IL-18 is a key mediator of downstream inflammasome effects.
IL-18 is only biologically active in its "free" or unbound form, dissociated from its "binding protein" - IL-18 Binding Protein (BP).
As such, measurement of Free IL-18 requires measurement of multiple parameters: Total IL-18, IL-18 BP and IL-18/BP-Complex.
This study aims to calculate the Free IL-18 levels in patients with and without COVID-19 (case-control aspect of the study) as well as in patients with varying degrees of COVID-19 severity (cohort aspect of the study), as determined by degree of lymphopaenia (how low the white cells of the body are), which has been shown to be an excellent marker of severity in COVID-19 disease.
Study 1 will be a case-control study to assess the association of COVID-19 with free IL-18 (primary risk factor) and other parameters of IL-18 complex (secondary risk factors) including Total IL-18, IL-18/BP Complex, IL-18 Binding Protein (BP) (secondary outcomes). Cases will be COVID-19 positive patients presenting to the hospital with COVID-19 symptoms. Controls will be COVID-19 negative patients presenting to the hospital with COVID-19 symptoms.
Study 2A will be a cohort study of admitted COVID-19 patients that will assess the relationship between change in free IL-18 level with change in COVID19 severity as measured by the degree of lymphopaenia over the duration of admission.
Study 2B will be a cross sectional analysis of the cohort study of admitted COVID-19 patients that will assess the relationship between free IL-18 level and COVID19 severity, as measured by degree of lymphopaenia, at days 10 and 15 of the disease.
Past studies have demonstrated an important role for interleukins downstream of IL-18 such as IL-6, and other interleukins concurrently released with IL-18, such as IL-1B. The aim of this study is to therefore consider what is the possible pathogenetic role of IL-18 in COVID-19, and whether it could potentially constitute a suitable drug target.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
20/SC/0316
Date of REC Opinion
16 Sep 2020
REC opinion
Further Information Favourable Opinion