The complement system in COVID-19

In this thesis, complement activation in COVID-19 was described and the effect of targeting complement factor C5a with the monoclonal antibody vilobelimab in severely and critically ill COVID-19 patients. The aim was to determine the effect of vilobelimab on mortality and safety in critically ill COVID-19 patients, to assess its effects on biomarkers of inflammation and coagulation in severely and critically ill COVID-19 patients, and to analyse its pharmacokinetics. In this thesis, it was shown that vilobelimab improved survival in critically ill, mechanically ventilated COVID-19 patients. Vilobelimab was found to efficiently inhibit C5a in severely and critically ill COVID-19 patients, without evidence of immunogenicity in critically ill COVID-19 patients. Finally, vilobelimab was shown to decrease the inflammatory response by lowering concentrations of CXCL8 over time. Further research should investigate whether different subphenotypes in COVID-19 respond differently to vilobelimab treatment and focus on the role of C5a and C5a inhibition in other viral infections that lead to ARDS.