Hyper inflammation of the lungs can increase disease severity, even in a young population lacking co-morbidities. These individuals, sometimes without prior medical history, end up at the ICU and require (invasive) respiratory support. It has been postulated that this is mediated by a dysregulated immune system, but a complete mechanistic understanding is currently lacking. However, it is known that viral, bacterial and fungal infections can result in a cytokine storm and this coincides with an increase of interleukin-6 (IL-6). Once IL-6 interacts with its receptor its activity on target cells is enhanced, resulting in an increase in inflammation. Several preliminary studies suggest that IL-6 levels are increased in COVID-19 patients at a progressed disease state.
A Cytokine storm is:
- An overreaction of the immune system on the virus in a small percentage of Covid-19 patients admitted to the ICU with severe respiratory symptoms
- Associated with a sustained increase of the cytokine interleukin-6 (IL-6) which has a wide range of biological effects on hepatocytes, hemapoietic cells, vascular endothelial cells, immune cells and many others resulting in pro-inflammatory signals and eventually tissue damage.
Blocking IL-6 could be beneficial for patients by improving oxygenation and reduction of key inflammatory parameters.
The main purpose of this study is to investigate the effect of individually or simultaneously blocking IL-6 and IL-1 on blood oxygenation and cytokine release syndrome in patients infected with SARS-CoV-2. In particular, this study will use Tocilizumab (an anti-IL6 antibody), Siltuximab (a chimeric antibody that neutralizes IL-6) and Anakinra (a modified version of the IL-1 receptor antagonist).
The proposed study is focused on:
- Epidemic control: Novel molecular insights and treatment options in COVID-19 patients to guide treatment of progressed disease stages, with a particular focus on patients with hypoxia that show signs of cytokine release syndrome.
Facts & Figures
Pathogen epidemics will be controlled or new molecular insights are translated into health and prevention policies
Contribution to the project
Patient inclusion will occur at UZGent. At the same time, blood samples will be used to determine the amount of peripheral blood mononuclear cells (e.g. monocytes and dendritic cells). Cytokine and chemokine levels will also be determined at the VIB-UGent Center for Inflammation Research.
Finally, here the effect of therapy on transcriptional programming of immune cells (single cells RNA-seq) will also be performed.
The objective of the VIB-GC program is to significantly increase the societal impact of VIB, taking its scientific leadership to the next level of global visibility. Strategies between partners towards sharing of capabilities (samples, data, infrastructure) are prerequisite and motivated within the VIB GCP, aligned with the general principles of RRI and the Open Science policy of VIB in particular.
Additionally, a close collaboration exists between the central biobank and partner institution: UZGent.
This will be the first head-to-head trial in which two distinct IL-6 blockers will be compared. This could severely reduce the pressure on the ICU in the short term and reduce morbidity of affected patients on the longer term.
Bart Lambrecht highlights why cytokines are important targets of patients infected with SARS-CoV-2: “Research from China and Italy shows that more cytokines are present in patients that are being ventilated on intensive care. Sometimes these cytokines are present in such great numbers that we call it a ‘cytokine storm’. We hope that we can prevent patients from needing to go to intensive care by an early start of anti-cytokine therapy that might prevent or mitigate a cytokine storm.”