Kjellberg Anders, Zhao Allan, Lussier Anna, Hassler Adrian, Al-Ezerjawi Sarah, Boström Emil, Catrina Sergiu-Bogdan, Bergman Peter, Rodriguez-Wallberg Kenny Alexandra, Lindholm Peter
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Perioperative Medicine and Intensive Care Medicine, Karolinska University Hospital, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Pulm Pharmacol Ther. 2024 Dec;87:102330. doi: 10.1016/j.pupt.2024.102330. Epub 2024 Oct 10.
Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed. In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed. Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO/FiO was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01). We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls. TRIAL REGISTRATION: NCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).
需要能够逆转重症 COVID-19、针对宿主-病毒免疫反应的免疫调节药物。在这项随机对照临床试验的探索性子研究中，瑞典一家大学医院的中度急性呼吸窘迫综合征的重症 COVID-19 患者被随机分配（1:1）至高压氧治疗（HBOT）组加最佳治疗方案，或最佳治疗方案（对照组）。随访时间为 30 天。在最初七天内，以 2.4 绝对大气压（ATA）进行五次 HBOT 治疗，每次持续 80 分钟。分析了临床结局、炎症标志物以及外周血单个核细胞的全转录组测序（RNAseq）。在 2020 年 12 月 3 日至 2021 年 5 月 17 日期间，23 例患者被随机分组，17 例患者接受分析。RNA 测序显示，在第 7 天与基线相比，HBOT 组有 791 个差异表达基因，而对照组有 46 个。基因集富集分析显示 HBOT 组存在与内质网应激（ERS）相关的独特转录组特征。HBOT 组患者恢复更快，平均住院时间更短，分别为 16 天和 26 天（95.99%CI -16 - 0），p = 0.045。HBOT 组的国家早期预警评分（NEWS）更低（方差分析，F[8, 120] = 3.817，p < 0.001），且 HBOT 组的 PaO/FiO 更高（混合效应模型，F[8, 94] = 2.900，p < 0.01）。我们展示了在接受 HBOT 治疗的重症 COVID-19 患者中与病毒诱导的 ERS 相关的独特转录组特征。这一发现与积极的临床结局相关；与对照组相比，接受 HBOT 治疗的患者恢复更快且住院时间缩短。试验注册：NCT04327505（2020 年 3 月 31 日）和 EudraCT 2020 - 001349 - 37（2020 年 4 月 24 日）。
