PLoS ONE (Jan 2021)

Eculizumab in patients with severe coronavirus disease 2019 (COVID-19) requiring continuous positive airway pressure ventilator support: Retrospective cohort study.

  • Piero Ruggenenti,
  • Fabiano Di Marco,
  • Monica Cortinovis,
  • Luca Lorini,
  • Silvia Sala,
  • Luca Novelli,
  • Federico Raimondi,
  • Sara Gastoldi,
  • Miriam Galbusera,
  • Roberta Donadelli,
  • Caterina Mele,
  • Rossella Piras,
  • Marina Noris,
  • Valentina Portalupi,
  • Laura Cappelletti,
  • Camillo Carrara,
  • Federica Tomatis,
  • Silvia Bernardi,
  • Annalisa Perna,
  • Tobia Peracchi,
  • Olimpia Diadei,
  • Ariela Benigni,
  • Giuseppe Remuzzi

DOI
https://doi.org/10.1371/journal.pone.0261113
Journal volume & issue
Vol. 16, no. 12
p. e0261113

Abstract

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BackgroundComplement activation contributes to lung dysfunction in coronavirus disease 2019 (COVID-19). We assessed whether C5 blockade with eculizumab could improve disease outcome.MethodsIn this single-centre, academic, unblinded study two 900 mg eculizumab doses were added-on standard therapy in ten COVID-19 patients admitted from February 2020 to April 2020 and receiving Continuous-Positive-Airway-Pressure (CPAP) ventilator support from ≤24 hours. We compared their outcomes with those of 65 contemporary similar controls. Primary outcome was respiratory rate at one week of ventilator support. Secondary outcomes included the combined endpoint of mortality and discharge with chronic complications.ResultsBaseline characteristics of eculizumab-treated patients and controls were similar. At baseline, sC5b-9 levels, ex vivo C5b-9 and thrombi deposition were increased. Ex vivo tests normalised in eculizumab-treated patients, but not in controls. In eculizumab-treated patients respiratory rate decreased from 26.8±7.3 breaths/min at baseline to 20.3±3.8 and 18.0±4.8 breaths/min at one and two weeks, respectively (pConclusionsIn patients with severe COVID-19, eculizumab safely improved respiratory dysfunction and decreased the combined endpoint of mortality and discharge with chronic complications. Findings need confirmation in randomised controlled trials.