Abstract
A dysregulated immune response with hyperinflammation is observed in patients with severe coronavirus disease 2019 (COVID-19). The aim of the present study was to assess the safety and potential benefits of human recombinant C1 esterase inhibitor (conestat alfa), a complement, contact activation and kallikrein-kinin system regulator, in severe COVID-19. Patients with evidence of progressive disease after 24 h including an oxygen saturation <93% at rest in ambient air were included at the University Hospital Basel, Switzerland in April 2020. Conestat alfa was administered by intravenous injections of 8400 IU followed by 3 additional doses of 4200 IU in 12-h intervals. Five patients (age range, 53–85 years; one woman) with severe COVID-19 pneumonia (11–39% lung involvement on computed tomography scan of the chest) were treated a median of 1 day (range 1–7 days) after admission. Treatment was well-tolerated. Immediate defervescence occurred, and inflammatory markers and oxygen supplementation decreased or stabilized in 4 patients (e.g., median C-reactive protein 203 (range 31–235) mg/L before vs. 32 (12–72) mg/L on day 5). Only one patient required mechanical ventilation. All patients recovered. C1INH concentrations were elevated before conestat alfa treatment. Levels of complement activation products declined after treatment. Viral loads in nasopharyngeal swabs declined in 4 patients. In this uncontrolled case series, targeting multiple inflammatory cascades by conestat alfa was safe and associated with clinical improvements in the majority of severe COVID-19 patients. Controlled clinical trials are needed to assess its safety and efficacy in preventing disease progression.
Highlights
The current pandemia of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a major global health challenge
The clinical spectrum of COVID-19 ranges from asymptomatic carriers to respiratory failure
Investigating a regulator of the complement system (CS), CAS, and kallikrein-kinin system (KKS) for the first time in severe COVID-19, we report the experience of early administration of conestat alfa, a recombinant human C1 esterase inhibitor (C1INH), in non-critically ill patients to prevent deterioration
Summary
The current pandemia of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a major global health challenge. The clinical spectrum of COVID-19 ranges from asymptomatic carriers to respiratory failure. A dysregulated immune response with evidence of hyperinflammation is observed in patients with severe. Siddiqi et al suggested a disease stage model, where early disease is charaterized by infection and replication of the virus. Pulmonary involvement and marked hyperinflammation occur during the stage [2]. The exact factors promoting disease progression are not yet known. Sustained activation of the complement system (CS) induced by coronaviruses (CoV) seems to play a crucial role in this context
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
