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, 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

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.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
A. Chest X-ray at enrollment. The X-ray demonstrates the bilateral infiltration of the lungs leading to the diagnosis of bilateral interstitial pneumonia. B. Chest X-ray on day 19. The X-ray demonstrates a marked improvement of pneumonia with re-expansion of the lungs, bilaterally.
Fig. 2
Fig. 2
Biomarkers of systemic inflammation during AMY-101 treatment. Changes of biomarkers of systemic inflammation during the 14-day treatment period; WBC: white blood cells; ANC: absolute neutrophil count; ALC: absolute lymphocyte count; LDH: lactate de‑hydrogenase; CRP: C-reactive protein.
Fig. 3
Fig. 3
Changes of lung function during the 14-day treatment period, displayed as need of oxygen support; Panel A: Continuous Positive Air-Pressure, measured as hours of C-PAP per 12 h; Panel B: % pf Fraction of Inspired Oxygen in Ventimask.

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