Introduction Patients with COVID-19-related acute respiratory distress syndrome (ARDS) show limited systemic hyperinflammation, but immunomodulatory treatments are effective. Little is known about the inflammatory response in the lungs and if this could be targeted using high-dose steroids (HDS). We aimed to characterise the alveolar immune response in patients with COVID-19-related ARDS, to determine its association with mortality, and to explore the association between HDS treatment and the alveolar immune response. Methods In this observational cohort study, a comprehensive panel of 63 biomarkers was measured in repeated bronchoalveolar lavage (BAL) fluid and plasma samples of patients with COVID-19 ARDS. Differences in alveolar–plasma concentrations were determined to characterise the alveolar inflammatory response. Joint modelling was performed to assess the longitudinal changes in alveolar biomarker concentrations, and the association between changes in alveolar biomarker concentrations and mortality. Changes in alveolar biomarker concentrations were compared between HDS-treated and matched untreated patients. Results 284 BAL fluid and paired plasma samples of 154 patients with COVID-19 were analysed. 13 biomarkers indicative of innate immune activation showed alveolar rather than systemic inflammation. A longitudinal increase in the alveolar concentration of several innate immune markers, including CC motif ligand (CCL)20 and CXC motif ligand (CXCL)1, was associated with increased mortality. Treatment with HDS was associated with a subsequent decrease in alveolar CCL20 and CXCL1 levels. Conclusions Patients with COVID-19-related ARDS showed an alveolar inflammatory state related to the innate host response, which was associated with a higher mortality. HDS treatment was associated with decreasing alveolar concentrations of CCL20 and CXCL1. Data are available upon reasonable request. De-identified participant data with data dictionary can be shared after approval of a proposal with a signed data access agreement and always in collaboration with the study group.

中文翻译：

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COVID-19危重患者持续的肺泡炎症反应与死亡率相关

简介 患有 COVID-19 相关急性呼吸窘迫综合征 (ARDS) 的患者表现出有限的全身过度炎症，但免疫调节治疗是有效的。对于肺部的炎症反应以及是否可以使用高剂量类固醇 (HDS) 来控制炎症反应，人们知之甚少。我们的目的是表征 COVID-19 相关 ARDS 患者的肺泡免疫反应，以确定其与死亡率的关系，并探讨 HDS 治疗与肺泡免疫反应之间的关联。方法 在这项观察性队列研究中，对 COVID-19 ARDS 患者的重复支气管肺泡灌洗 (BAL) 液体和血浆样本中的 63 种生物标志物进行了综合检测。确定肺泡血浆浓度的差异来表征肺泡炎症反应。进行联合建模以评估肺泡生物标志物浓度的纵向变化以及肺泡生物标志物浓度变化与死亡率之间的关联。比较 HDS 治疗和匹配的未治疗患者之间肺泡生物标志物浓度的变化。结果 对 154 名 COVID-19 患者的 284 份 BAL 液体和配对血浆样本进行了分析。13 种指示先天免疫激活的生物标志物显示肺泡而不是全身炎症。几种先天免疫标记物（包括 CC 基序配体 (CCL)20 和 CXC 基序配体 (CXCL)1）肺泡浓度的纵向增加与死亡率增加相关。HDS 治疗与随后肺泡 CCL20 和 CXCL1 水平下降相关。结论 COVID-19 相关 ARDS 患者表现出与先天宿主反应相关的肺泡炎症状态，这与较高的死亡率相关。HDS 治疗与 CCL20 和 CXCL1 肺泡浓度降低相关。数据可根据合理要求提供。在批准具有签署的数据访问协议的提案后，可以共享带有数据字典的去识别化参与者数据，并且始终与研究组合作。