单细胞HLA-DR表达轨迹的联合建模预测严重的SARS-CoV-2患者的28天死亡率
Gaelle Baudemont1, Coralie Tardivon2,3, Guillaume Monneret4,5
1Université Paris Cité and Université Sorbonne Paris Nord, Inserm, IAME, Paris, France.
CPT: pharmacometrics & systems pharmacology
|June 5, 2024
概括
研究COVID-19患者的免疫细胞标记物显示,单细胞HLA-DR表达 (mHLA-DR) 预测了生存. 较高的mHLA-DR水平与重症监护室 (ICU) 死亡风险降低相关.
科学领域:
- 免疫学 免疫学 免疫学
- 关键护理医学 关键护理医学
- 传染性疾病 传染性疾病
背景情况:
- COVID-19大流行严重影响了重症监护室 (ICU),突出显示了严重病例的免疫系统调节失调,其特征是高炎症和免疫抑制.
- 了解免疫学参数的预后价值对于管理重症COVID-19患者至关重要.
研究的目的:
- 调查细胞免疫学参数的轨迹与入住ICU的COVID-19患者的存活率之间的关联.
- 评估单细胞HLA-DR表达 (mHLA-DR) 动力学对28天死亡率的预测性能.
主要方法:
- 在REA-IMMUNO-COVID队列 (538名COVID-19ICU患者) 的数据上使用了联合建模方法.
- 在ICU入院后的第一个月内,五次收集了mHLA-DR,中性粒细胞,淋巴细胞和CD4+/CD8+T细胞子集的纵向测量.
- 单变体和多变体关节模型被用于分析与28天生存和出院相关的生物标志物动力学.
主要成果:
- 较高的mHLA-DR表达与较低的28天死亡风险显著相关.
- 预测的mHLA-DR极点切线为5414 Ab/C,显示D28死亡率预测曲线下的面积 (AUC) 为0.70.
- 动态预测使用mHLA-DR动力学到第7,12和20天的动态预测表明AUC有所改善 (分别为0.82,0.81和0.84),这表明预测准确度提高了更多的数据点.
结论:
- 在严重的COVID-19后减少mHLA-DR表达是增加28天死亡率的独立预测因素,即使考虑到临床混因素.
- 结合mHLA-DR动态的联合模型为预测D28死亡率提供了足够的歧视,随着更多生物标志物数据的可用性,性能得到了改善.
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