Lead
Patients with diabetes who are overweight have a particularly bad outcome if infected with SARS-CoV-2. A possible explanation may be overactivation of the IL-1beta system. Indeed, metabolic stress and SARS-CoV-2 both induce IL-1beta secretion, which may lead to excess mortality in these vulnerable patients.

Lay summary

Background

Activation of the innate immune system by IL-1 is apparent at all stages of development of obesity-associated type 2 diabetes and its complications. Accordingly, IL-1 antagonism has been shown to improve glycaemia and to lessen cardiovascular complications. Several studies have shown that coronavirus stimulates the NLRP3 inflammasome, leading to a severe inflammatory response by the IL-1beta pathway. We hypothesise that both mechanisms synergise, leading to deleterious hyperinflammation as is often observed in obese diabetic patients infected with SARS-CoV-2.

Research aims

This is a multicentre, randomised, double-blind, placebo-controlled study to assess the efficacy of canakinumab compared with placebo in hospitalised overweight patients with COVID-19 and type 2 diabetes. The study will randomise patients from eight Swiss hospitals to canakinumab or placebo, in addition to standard of care per local practice, which may include antiviral treatment (e.g. remdesivir), corticosteroids and/or supportive care but no other immunomodulatory medications.

Expected results and envisaged products

We hope to see beneficial effects for patients on mortality, requirement of ventilation and intensive care medicine as well as on duration of hospitalisation. Our findings may have consequences for the treatment of patients with diabetes and COVID-19 as well as for other viral infections.

Specific contribution to tackle the current pandemic

Our contribution to the current pandemic may be to improve treatment of the disease as detailed above. We will also examine whether putative long-term complications such as shortness of breath and loss of smell can be prevented by canakinumab. Last but not least, we expect to see confirmation of the beneficial effects of canakinumab and other IL-1 blockers on blood glucose, as observed in previous diabetes studies.