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

Highlights • The authors describe a transplant-listed PWCF who developed severe COVID-19. • A blended inflammatory immunophenotype was observed in both blood and lung. • She received intravenous alpha-1 antitrypsin (AAT) based on biological plausibility. • Systemic and airway inflammatory markers decreased following therapy. • Decreased inflammation was matched by clinical and radiographic improvement.
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)-1β, IL-6, IL-8, and soluble TNF receptor 1 (sTNFR1) were assessed at regular intervals in plasma, with IL-1β, 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-1β 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.