ImmunoTargets and Therapy (Jul 2021)
Complement Inhibition and COVID-19: The Story so Far
Abstract
Sofiane Fodil,1 Djillali Annane1– 3 1Department of Intensive Care, Hôpital Raymond Poincaré (APHP), Garches, 92380, France; 2Laboratory of Infection & Inflammation _ U1173, School of Medicine Simone Veil, University Versailles Saint Quentin _ University Paris Saclay, INSERM, Montigny-Le-Bretonneau, 78180, France; 3FHU SEPSIS (Saclay and Paris Seine Nord Endeavour to PerSonalize Interventions for SEPSIS), AP-HP, University Versailles Saint Quentin _ University Paris Saclay, INSERM, Garches, 92380, FranceCorrespondence: Djillali AnnaneDepartment of Intensive Care, Hôpital Raymond Poincaré (APHP), 104 Boulevard Raymond Poincaré, Garches, 92380, FranceTel +33 147107787Email [email protected]: Acute respiratory distress syndrome (ARDS) is the most severe complication of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus (SARS CoV) 2. The mechanisms underlying the progression from asymptomatic disease to pneumonia and ARDS are complex and by far unelucidated. As for bacterial sepsis, the release of damage associated molecular patterns and pathogen associated molecular patterns triggers activation of the complement cascade. Subsequently, overexpressed anaphylatoxins recruit inflammatory cells in the lung and other organs and contribute initiating and amplifying a vicious circle of thromboinflammation causing organs damage and eventually death. Preclinical and observational studies in patients with COVID-19 provided evidence that complement inhibition effectively may attenuate lung and systemic inflammation, restore the coagulation/fibrinolysis balance, improve organs function and eventually may save life. Ongoing Phase 2/3 trials should elucidate the benefit to risk profile of complement inhibitors and may clarify the optimal targets in the complement cascade.Keywords: complement system, cytokines, anaphylatoxins, monoclonal antibodies
