Szabó Bálint Gergely, Reményi Péter, Tasnády Szabolcs, Korózs Dorina, Gopcsa László, Réti Marienn, Várkonyi Andrea, Sinkó János, Lakatos Botond, Szlávik János, Bekő Gabriella, Bobek Ilona, Vályi-Nagy István
Departmental Group of Infectious Diseases, Department of Haematology and Internal Medicine, Semmelweis University, H-1097 Budapest, Hungary.
South Pest Central Hospital, National Institute of Haematology and Infectious Diseases, Albert Florian út 5-7., H-1097 Budapest, Hungary.
J Clin Med. 2023 Jul 29;12(15):5000. doi: 10.3390/jcm12155000.
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. 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. 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. 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. ClinicalTrials.gov NCT05882331 (retrospectively registered).
对于因严重和危重型新型冠状病毒肺炎（COVID-19）住院且对抗病毒和免疫调节药物无反应的成年患者，最佳治疗方法尚未明确。我们的目的是评估在这种情况下体外光化学疗法（ECP）的可行性和安全性。2021年至2022年期间，在一家COVID-19三级转诊中心进行了一项前瞻性、单中心研究。对诊断为COVID-19的患者进行筛查，连续纳入尽管使用了瑞德西韦、地塞米松和免疫调节药物（托珠单抗、巴瑞替尼、芦可替尼），但仍符合预定义的临床和生化标准且无反应超过5天的重症或危重症病例。患者入组后，每周连续两天进行两次ECP治疗，共进行2周。从研究入组开始按照方案对患者进行随访，并在治疗结束（EOT）+28天时评估临床、病毒学和影像学结果。总共纳入了7名患者。入组时，7名患者中有4名（57.1%）入住重症监护病房（ICU），所有患者均存在持续的细胞因子风暴。此外，3/7（42.9%）患者胸部CT有影像学进展。在EOT+28天时，2/7（28.6%）患者因与ECP无关的原因死亡。在幸存者中，未观察到额外的入住重症监护病房需求或影像学进展，1/5（20.0%）患者可脱机有创机械通气。所有患者均实现全血严重急性呼吸综合征冠状病毒2（SARS-CoV-2）核糖核酸血症清除，而3/7（42.9%）患者呼吸道SARS-CoV-2核糖核酸不再可检测到。根据免疫生物标志物分析，ECP主要促使血浆白细胞介素-6（IL-6）和白细胞介素-17A水平降低，以及外周血免疫细胞亚群的生理性再生，尤其是CD8+/CD45RO+记忆T细胞。未发现安全信号。对于因严重或危重型COVID-19住院且对药物干预无反应的成年人，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方法。ClinicalTrials.gov NCT05882331（回顾性注册）
