The first case of COVID-19 treated with the complement C3 inhibitor AMY-101

Sara Mastaglio; Annalisa Ruggeri; Antonio M Risitano; Piera Angelillo; Despina Yancopoulou; Dimitrios C Mastellos; Markus Huber-Lang; Simona Piemontese; Andrea Assanelli; Cecilia Garlanda; John D Lambris; Fabio Ciceri

doi:10.1016/j.clim.2020.108450

The first case of COVID-19 treated with the complement C3 inhibitor AMY-101

Clin Immunol. 2020 Jun:215:108450. doi: 10.1016/j.clim.2020.108450. Epub 2020 Apr 29.

Affiliations

¹ Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
² Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy.
³ Amyndas Pharmaceuticals, Glyfada, Greece.
⁴ National Center for Scientific Research 'Demokritos', Aghia Paraskevi, Athens, Greece.
⁵ Institute of Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany.
⁶ IRCCS Humanitas Clinical and Research Center, Milan, Italy; Humanitas University, Milan, Italy.
⁷ Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: [email protected].
⁸ Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; University Vita Salute San Raffaele, Milan, Italy. Electronic address: [email protected].

Abstract

Acute respiratory distress syndrome (ARDS) is a devastating clinical manifestation of COVID-19 pneumonia and is mainly based on an immune-driven pathology. Mounting evidence suggests that COVID-19 is fueled by a maladaptive host inflammatory response that involves excessive activation of innate immune pathways. While a "cytokine storm" involving IL-6 and other cytokines has been documented, complement C3 activation has been implicated as an initial effector mechanism that exacerbates lung injury in preclinical models of SARS-CoV infection. C3-targeted intervention may provide broader therapeutic control of complement-mediated inflammatory damage in COVID-19 patients. Herein, we report the clinical course of a patient with severe ARDS due to COVID-19 pneumonia who was safely and successfully treated with the compstatin-based complement C3 inhibitor AMY-101.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antiviral Agents / therapeutic use
Atrial Fibrillation / drug therapy
Atrial Fibrillation / immunology
Atrial Fibrillation / pathology
Atrial Fibrillation / virology
Betacoronavirus / drug effects*
Betacoronavirus / immunology
Betacoronavirus / pathogenicity
COVID-19
Complement Activation / drug effects*
Complement C3 / antagonists & inhibitors*
Complement Inactivating Agents / therapeutic use*
Coronavirus Infections / drug therapy*
Coronavirus Infections / immunology
Coronavirus Infections / pathology
Coronavirus Infections / virology
Humans
Hypercholesterolemia / drug therapy
Hypercholesterolemia / immunology
Hypercholesterolemia / pathology
Hypercholesterolemia / virology
Hypertension / drug therapy
Hypertension / immunology
Hypertension / pathology
Hypertension / virology
Lung / drug effects
Lung / immunology
Lung / pathology
Lung / virology
Male
Pandemics
Peptides, Cyclic / therapeutic use*
Pneumonia, Viral / drug therapy*
Pneumonia, Viral / immunology
Pneumonia, Viral / pathology
Pneumonia, Viral / virology
SARS-CoV-2
Treatment Outcome

Substances

Antiviral Agents
Complement C3
Complement Inactivating Agents
Peptides, Cyclic
compstatin

Grants and funding

P01 AI068730/AI/NIAID NIH HHS/United States