Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of ALI/ARDS patients with COVID-19
Ruiying Wang,
Junping Yin,
Jian Li,
Xueli Bai,
Hu Liu,
Mengyu Cheng,
Lei Wang,
Yuan Chen,
Shuang Wei,
Xiansheng Liu
Affiliations
Ruiying Wang
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China
Junping Yin
Institute of Molecular Medicine and Experimental Immunology, University Clinic of Rheinische Friedrich-Wilhelms-University, Bonn, Germany
Jian Li
Institute of Molecular Medicine and Experimental Immunology, University Clinic of Rheinische Friedrich-Wilhelms-University, Bonn, Germany
Xueli Bai
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
Hu Liu
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
Mengyu Cheng
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
Lei Wang
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
Yuan Chen
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1096 Jiefang Road, Wuhan, Hubei, China
Shuang Wei
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China; Department of Pulmonary and Critical Care Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Corresponding author.
Xiansheng Liu
Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Sino-German Joint Oncological Research Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, Shanxi, China; Department of Pulmonary and Critical Care Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Corresponding author. Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Background: Sivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS. Methods: A retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO2), the ratio of PaO2 to the fraction of inspired oxygen (PaO2/FiO2), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia. Results: In the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, P < 0.001), more ARDS patients (4.9 % vs. 0.43 %, P < 0.001), and more patients with interstitial lung disease (4.9 % vs. 1.49 %, P = 0.023), but fewer patients with stroke (17.65 % vs. 19.86 %, P < 0.001). Oxygen therapy rates were similar between the groups (79.41 % vs. 80.95 %, P = 0.9). The relative risk reduction in 30-day mortality was 88.45 % (95 % confidence interval [CI] 81.23%–93.21 %) for severe/critical COVID-19 patients treated with sivelestat. Sivelestat significantly decreased cytokine levels of interferon alpha (IFNα), interleukin-1 beta (IL-1β), and interleukin-2 (IL-2).In the sivelestat group, the mortality rate was significantly reduced with standard oxygenation and HFNC therapy(P < 0.05). The treatment with sivelestat did not increase side effects. Conclusion: The administration of the neutrophil elastase inhibitor sivelestat may improve clinical outcomes in COVID-19 patients with ALI/ARDS. These findings suggest that sivelestat could be considered an effective treatment option to alleviate pulmonary inflammatory injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
