The bradykinin-2 receptor antagonist, icatibant, improves lung function in patients with SARS-CoV2 associated ARDS - First results of a prospective off-label use patient-related observational study.

SARS-CoV2-associated adult respiratory distress syndrome (COVID19-ARDS) frequently leads to fatal respiratory failure in COVID19. Currently, there is no curative treatment option for severe COVID19-ARDS other than mechanical ventilation therapy and extracorporal membrane oxygenation (ECMO). We investigated whether modification of the kallikrein-kinin system in vivo attenuates the progression of SARS-CoV2-induced ARDS. The aim of the study was to investigate the effect of blockade of the B2R on the course of COVID19-ARDS. In an observational study including 53 COVID19-ARDS patients, patients received the bradykinin-2-receptor antagonist (B2RAg) icatibant. After icatibant substitution, respiratory rate in COVID19-ARDS reduced by a maximum of 32% (24.9/min to 16.8/min) with a concomitant reduction in oxygen substitution by 59% (6.1 LO₂/min to 2.5 LO₂/min). The data show that the use of icatibant in the early phase of COVID19-ARDS is suitable to stabilize pulmonary gas exchange. Furthermore, early icatibant substitution seems to be able to reduce the rate of necessary invasive ventilation in COVID19-ARDS. Observational data suggest that inhibition of bradykinin signalling leads to stabilization of lung function in SARS-CoV2-associated ARDS. Further prospective placebo-controlled studies are needed to investigate the impact of the kallikrein-kinin system on the development of COVID19-ARDS in vivo.