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 120mg/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.

中文翻译：

---

严重细胞动力学 COVID-19 并发囊性纤维化的 ALPHA-1 抗胰蛋白酶

背景 囊性纤维化 (CF) 中严重 COVID-19 的临床过程尚不完全清楚。我们描述了使用 alpha-1 抗胰蛋白酶 (AAT) 作为挽救治疗的危重 CF (PWCF) 患者，该患者在等待肺移植时患上了 COVID-19。方法 IV AAT 以 120mg/kg/周的剂量给药，连续 4 周。定期评估血浆中白细胞介素 (IL)-1β、IL-6、IL-8 和可溶性 TNF 受体 1 (sTNFR1) 的水平，使用 IL-1β、IL-6、IL-8 和中性粒细胞弹性蛋白酶 (NE ) 在气道分泌物中测量的活性。将水平与基线和历史严重恶化测量值进行比较。结果 与之前的恶化和基线水平相比，全身和气道炎症标志物增加，特别是 IL-6、IL-1β 和 NE 活性。每次服用 AAT 后，观察到每个炎症参数的快速下降。这些与显着的临床和影像学改善相匹配。结论 该结果支持进一步研究 AAT 作为 COVID-19 治疗剂，并重新探索其在 CF 中的用途。