Alpha-1 antitrypsin for cystic fibrosis complicated by severe cytokinemic COVID-19

Background: The clinical course of severe COVID-19 in cystic fibrosis (CF) is incompletely understood. We describe the use of alpha-1 antitrypsin (AAT) as a salvage therapy in a critically unwell patient with CF (PWCF) who developed COVID-19 while awaiting lung transplantation. Methods: IV AAT was administered at 120 mg/kg/week for 4 consecutive weeks. Levels of interleukin (IL)-1 beta, IL-6, IL-8, and soluble TNF receptor 1 (sTNFR1) were assessed at regular intervals in plasma, with IL-1 beta, IL-6, IL-8 and neutrophil elastase (NE) activity measured in airway secretions. Levels were compared to baseline and historic severe exacerbation measurements. Results: Systemic and airway inflammatory markers were increased compared to both prior exacerbation and baseline levels, in particular IL-6, IL-1 beta and NE activity. Following each AAT dose, rapid decreases in each inflammatory parameter were observed. These were matched by marked clinical and radiographic improvement. Conclusions: The results support further investigation of AAT as a COVID-19 therapeutic, and re exploration of its use in CF. (C) 2020 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.