PDF(Pubmed)
Abstract：
Background: The optimal approach for adult patients hospitalized with severe and critical coronavirus disease 2019 (COVID-19), non-responsive to antiviral and immunomodulatory drugs, is not well established. Our aim was to evaluate feasibility and safety of extracorporeal photopheresis (ECP) in this setting. Methods: A prospective, single-center investigational study was performed between 2021 and 2022 at a tertiary referral center for COVID-19. Patients diagnosed with COVID-19 were screened, and cases with severe or critical disease fulfilling pre-defined clinical and biochemical criteria of non-response for >5 days, despite remdesivir, dexamethasone and immunomodulation (tocilizumab, baricitinib, ruxolitinib), were consecutively enrolled. After patient inclusion, two ECP sessions on two consecutive days per week for 2 weeks were applied. Patients were followed-up per protocol from study inclusion, and clinical, virological and radiological outcomes were assessed at the end of treatment (EOT) +28 days. Results: A total of seven patients were enrolled. At inclusion, four out of seven (57.1%) were admitted to the ICU, all patients had ongoing cytokine storm. Additionally, 3/7 (42.9%) had radiological progression on chest CT. At EOT+28 days, 2/7 (28.6%) patients died due to non-ECP-related causes. Among the survivors, no additional requirement for intensive care unit admission or radiological progression was observed, and invasive mechanical ventilation could be weaned off in 1/5 (20.0%). All patients achieved whole-blood SARS-CoV-2 RNAemia clearance, while 3/7 (42.9%) no longer showed detectable respiratory SARS-CoV-2 RNA. According to immune biomarker profiling, ECP mainly facilitated a decrease in plasma IL-6 and IL-17A levels, as well as the physiological regeneration of peripheral blood immunocyte subpopulations, notably CD8+/CD45RO+ memory T-cells. No safety signals were identified. Conclusions: ECP appears to be a safe and feasible option for adults hospitalized with severe or critical COVID-19 who do not respond to pharmacological interventions. Further trial data are warranted to assess its optimal use. Trial registration: ClinicalTrials.gov NCT05882331 (retrospectively registered).
摘要：
背景：2019年重症和危重症冠状病毒病住院成年患者的最佳治疗方法(COVID-19)，对抗病毒和免疫调节药物无反应，不是很确定。我们的目的是评估在这种情况下体外光分离术（ECP）的可行性和安全性。方法：前瞻性，单中心调查研究于2021年至2022年在COVID-19三级转诊中心进行。对确诊为COVID-19的患者进行筛查，和严重或危重疾病的病例满足预定的临床和生化标准的无应答>5天，尽管Remdesivir,地塞米松和免疫调节（托珠单抗，baricitinib,ruxolitinib),连续登记。纳入患者后，我们应用了两次ECP疗程,每周连续两天,共2周.根据研究纳入的方案对患者进行随访，临床,在治疗结束(EOT)+28天评估病毒学和放射学结果.结果：共纳入7例患者。在纳入时，七分之四(57.1%)入住重症监护病房,所有患者都有持续的细胞因子风暴.此外,3/7（42.9％）在胸部CT上有放射学进展。在EOT+28天,2/7（28.6%）患者死于非ECP相关原因。在幸存者中,没有观察到重症监护病房入院或放射学进展的额外要求，有创机械通气可断奶的1/5(20.0%)。所有患者均获得全血SARS-CoV-2RNA血症清除，而3/7（42.9％）不再显示可检测的呼吸道SARS-CoV-2RNA。根据免疫生物标志物分析，ECP主要促进血浆IL-6和IL-17A水平的降低，以及外周血免疫细胞亚群的生理再生，特别是CD8+/CD45RO+记忆T细胞。没有确定安全信号。结论：对于重症或危重症COVID-19住院且对药物干预无反应的成人，ECP似乎是一种安全可行的选择。需要进一步的试验数据来评估其最佳使用。试验注册：ClinicalTrials.govNCT05882331（回顾性注册）。
