Patients with COVID-19 respiratory failure and IL-6 signalling pathway inactivation with Siltuximab: an observational cohort study

Severe COVID-19 is characterised by interstitial pneumonia and hyperinflammation, with elevated levels of pro-inflammatory cytokines, such as IL-6.

Effective treatments are urgently needed, and IL-6 is a rational target to reduce hyperinflammation.

An observational, control cohort, single-centre study, SISCO ( Siltuximab in Severe COVID-19 ), initiated at the Papa Giovanni XXIII Hospital in Bergamo, Italy included patients with COVID-19 confirmed by a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 [ SARS-CoV-2 ] RNA and interstitial pneumonia requiring ventilatory support.

Patients were treated with either best supportive care and Siltuximab ( Sylvant ) or best supportive care alone.

The main outcome was mortality in Siltuximab-treated patients compared with patients in the matched-control cohort.

Thirty patients received siltuximab, while 188 control patients received only best supportive care.

Siltuximab-treated patients were matched to 30 control patients using the propensity score analysis of baseline covariates.

The 30-day mortality rate was significantly lower in the Siltuximab-treated than the matched-control cohort patients ( hazard ratio, HR=0.462, 95% CI 0.221-0.965 ); p=0.0399 ).

The mean follow-up was 33.3 days ( range 7-58 days ) for the Siltuximab-treated patients and 22.8 days ( range 2-45 days ) for the control cohort.

Sixteen Siltuximab-treated patients were discharged from hospital, four remained on mechanical ventilation, and 10 patients died.

Patients with rapidly progressing COVID-19 respiratory failure requiring ventilatory support may benefit from treatment with Siltuximab to reduce mortality and cytokine-driven hyperinflammation associated with severe disease.

These findings require validation in a randomised controlled clinical trial. ( Xagena )