4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Inflammatix, Inc., Sunnyvale, CA, USA.
Crit Care. 2024 Mar 12;28(1):73. doi: 10.1186/s13054-024-04852-z.
Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial.
Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment.
At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013).
We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.
表型分类可能指导细菌和病毒脓毒症患者的免疫调节治疗。我们旨在确定与 SAVE-MORE 试验中接受 anakinra（人白细胞介素 1 受体拮抗剂）治疗的反应相关的免疫表型和转变。
在 SAVE-MORE 试验（NCT04680949）中，对因 SARS-CoV-2 引起的经 PCR 确诊的严重肺炎且血浆可溶性尿激酶型纤溶酶原激活物受体水平≥6ng/ml 的住院成年患者，在基线和治疗第 4 天和第 7 天使用之前定义的 33-messenger RNA 分类器进行特征描述，以在血液中分配免疫表型。终点是 anakinra 治疗引起的表型变化和进展为严重呼吸衰竭（SRF）。
在基线时，393 例患者中有 23.2%被指定为炎症性疾病，41.1%为适应性疾病，35.7%为凝血性疾病。与基线相比，只有 23.9%的患者在第 4 天和第 7 天被指定为相同的表型，而所有其他患者在表型之间发生转变。在 7 天的治疗期间，接受 anakinra 治疗的患者更有可能保持在适应性表型中（24.4% vs. 9.9%；p<0.001）。与安慰剂相比，在第 7 天，接受 anakinra 治疗的凝血性疾病患者也能预防 SRF（27.8% vs. 55.9%；p=0.013）。
我们确定了使用血液转录组定义的表型与 COVID-19 肺炎患者的 anakinra 治疗之间的关联，接受 anakinra 治疗的患者向与更好结局相关的表型转变，主要是适应性表型。试验注册 ClinicalTrials.gov，NCT04680949，2020 年 12 月 23 日。
