Cardiovascular Research Institute, University of California, San Francisco, California, United States.
Division of Biostatistics and Health Data Science, University of Minnesota, Minneapolis, Minnesota, United States.
Am J Physiol Lung Cell Mol Physiol. 2024 Nov 1;327(5):L607-L614. doi: 10.1152/ajplung.00350.2023. Epub 2024 Jul 30.
The soluble receptor for advanced glycation end-products (sRAGE) is a marker of alveolar type I cell injury associated with outcomes in COVID-19 pneumonia. How plasma sRAGE changes over time and whether it remains associated with long-term clinical outcomes beyond a single measurement in COVID-19 have not been well studied. We studied two cohorts in randomized clinical trials of monoclonal antibody treatment for COVID-19 (bamlanivimab and tixagevimab/cilgavimab). We first studied the association between baseline plasma sRAGE and 90-day clinical outcomes, which had been previously demonstrated in the bamlanivimab cohort, among hospitalized patients with COVID-19 supported with high-flow nasal oxygen (HFNO) or noninvasive ventilation (NIV) in the tixagevimab/cilgavimab study. Next, we investigated the relationship between sRAGE and 90-day outcomes and how plasma sRAGE changes over the first 3 days of hospitalization in both clinical trial cohorts. We found that plasma sRAGE in the highest quartile in the HFNO/NIV participants in the tixagevimab/cilgavimab trial was associated with a significantly lower rate of 90-day sustained recovery [recovery rate ratio = 0.31, 95% confidence interval (CI) = 0.14-0.71, = 0.005] and with a significantly higher rate of 90-day mortality (hazard ratio = 2.49, 95% CI = 1.15-5.43, = 0.021) compared with the lower three quartiles. plasma sRAGE in both clinical trial cohorts remained associated with 90-day clinical outcomes. The trajectory of sRAGE was not influenced by treatment assignment. Our results indicate that plasma sRAGE is a valuable prognostic marker in COVID-19 up to 3 days after initial hospital presentation. The soluble receptor for advanced glycation end-products (sRAGE) is a marker of alveolar type I epithelial cell injury associated with clinical outcomes in acute respiratory distress syndrome and, more recently, in hospitalized subjects with COVID-19. How plasma sRAGE changes over time and whether plasma sRAGE remains associated with long-term clinical outcomes beyond a single baseline measurement in patients with COVID-19 have not been well studied.
可溶性晚期糖基化终产物受体 (sRAGE) 是与 COVID-19 肺炎结局相关的肺泡 I 型细胞损伤的标志物。血浆 sRAGE 随时间的变化，以及它是否在 COVID-19 单次基线测量之外仍与长期临床结局相关，尚未得到很好的研究。我们研究了 COVID-19 单克隆抗体治疗的两项随机临床试验队列（巴美替尼和替加韦单抗/西加韦单抗）。我们首先研究了 COVID-19 住院患者中，基线血浆 sRAGE 与接受高流量鼻氧（HFNO）或无创通气（NIV）支持的患者 90 天临床结局之间的关联，这在巴美替尼队列中已有先前的研究结果。其次，我们研究了 sRAGE 与 90 天结局之间的关系，以及在两项临床试验队列中患者住院前 3 天内血浆 sRAGE 的变化。我们发现，在替加韦单抗/西加韦单抗试验中接受 HFNO/NIV 治疗的患者中，血浆 sRAGE 最高四分位数与 90 天持续康复率显著降低相关[康复率比=0.31，95%置信区间（CI）=0.14-0.71，=0.005]，与 90 天死亡率显著升高相关（风险比=2.49，95%CI=1.15-5.43，=0.021），与较低的三个四分位数相比。在两项临床试验队列中，血浆 sRAGE 仍与 90 天临床结局相关。sRAGE 的轨迹不受治疗分配的影响。我们的研究结果表明，在 COVID-19 患者初始住院后 3 天内，血浆 sRAGE 是一个有价值的预后标志物。可溶性晚期糖基化终产物受体（sRAGE）是急性呼吸窘迫综合征肺泡 I 型上皮细胞损伤的标志物，最近也与 COVID-19 住院患者的临床结局相关。血浆 sRAGE 随时间的变化，以及在 COVID-19 患者单次基线测量之外，血浆 sRAGE 是否仍与长期临床结局相关，尚未得到很好的研究。
