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托珠单抗超适应证用药联合辅助铁螯合剂治疗重症 COVID-19 肺炎患者的疗效:一项单中心经验。

Off-label tocilizumab and adjuvant iron chelator effectiveness in a group of severe COVID-19 pneumonia patients: A single center experience.

机构信息

Lucian Blaga University of Sibiu, Faculty of Medicine Sibiu, Academic Emergency Hospital Sibiu - Infectious Diseases Clinic, Sibiu.

Lucian Blaga University of Sibiu, Faculty of Medicine Sibiu, FOISOR Clinical Hospital of Orthopedics, Traumatology, and Osteoarticular TB Bucharest.

出版信息

Medicine (Baltimore). 2021 May 7;100(18):e25832. doi: 10.1097/MD.0000000000025832.

Abstract

Tocilizumab (TCZ), a monoclonal recombinant antibody against IL-6 receptor, is currently used in managing the cytokine release syndrome (CRS) that occurred in coronavirus disease 2019 (COVID-19) selected cases. The primary objective of our study was to establish the effectiveness of TCZ in patients with severe or critical severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia.We retrospectively analyzed 25 consecutive patients, admitted in the Academic Emergency Hospital Sibiu, Romania from April 1, 2020 until May 25, 2020, all with confirmed SARS-CoV-2 infection and severe pneumonia. All patients were treated off-label with TCZ, beside their standard care. Adjuvant iron chelator was associated in 11 patients.Six female and 19 male patients admitted in our hospital all with confirmed SARS-CoV-2 infection and severe pneumonia as defined by Chinese Centers for Disease Control and Prevention were enrolled in this study. Seventeen of the 25 enrolled patients (68%) were seriously ill requiring noninvasive ventilation or oxygen mask, and 8 cases (32%) were critically ill requiring invasive mechanical ventilation. All patients received TCZ, and also received hydroxychloroquine, and lopinavir/ritonavir 200/50 mg for 10 days. Adjuvant iron chelator (deferasirox - marketed as Exjade) was associated in 11 patients who had ferritin serum levels above 1000 ng/mL. No side effects were encountered during infusions or after TCZ. We observed a rapid increase in arterial oxygen saturation for 20 of the 25 cases (80%) with a favorable evolution toward healing. Survivors were younger than 60 years old (80%), had less comorbidities (10% no comorbidities, 70% with 1 or 2 comorbidities), lower serum ferritin levels (30% under 1000 ng/mL), and 50% had no serum glucose elevation. Our patients with CRS had no response to corticosteroid therapy. Five out of the 25 patients had an unfavorable evolution to death. The off-label use of TCZ in patients with severe or critically ill form of SARS-CoV-2 infection had good results in our study.Off-label use of TCZ in severe and critical cases of COVID-19 pneumonia is effective in managing the "cytokine storm." Better outcomes were noted in younger patients. Associated adjuvant iron chelators may contribute to a good outcome and needs to be confirmed in larger studies.

摘要

托珠单抗(TCZ)是一种针对白细胞介素 6 受体的单克隆重组抗体,目前用于治疗 2019 年冠状病毒病(COVID-19)选定病例中发生的细胞因子释放综合征(CRS)。我们研究的主要目的是确定 TCZ 在严重或危急的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)肺炎患者中的疗效。我们回顾性分析了 2020 年 4 月 1 日至 2020 年 5 月 25 日期间在罗马尼亚锡比乌学术急诊医院收治的 25 例连续患者,所有患者均确诊为 SARS-CoV-2 感染和严重肺炎。所有患者均接受 TCZ 治疗,未进行标签外治疗,并伴有标准护理。11 例患者联合使用辅助铁螯合剂。

纳入本研究的是我院收治的 6 例女性和 19 例男性患者,均符合中国疾病预防控制中心定义的严重 SARS-CoV-2 感染和严重肺炎。25 例纳入患者中,17 例(68%)病情严重,需要无创通气或氧气面罩,8 例(32%)病情危急,需要有创机械通气。所有患者均接受 TCZ 治疗,还接受羟氯喹和洛匹那韦/利托那韦 200/50mg 治疗 10 天。11 例患者铁蛋白血清水平>1000ng/ml,联合使用辅助铁螯合剂(地拉罗司 - 商品名 Exjade)。输注过程中和 TCZ 治疗后均未出现不良反应。25 例患者中有 20 例(80%)动脉血氧饱和度迅速升高,病情向愈合方向发展良好。幸存者均<60 岁(80%),合并症较少(10%无合并症,70%合并 1-2 种合并症),铁蛋白血清水平较低(30%<1000ng/ml),50%无血糖升高。我们的 CRS 患者对皮质类固醇治疗无反应。25 例患者中有 5 例病情恶化死亡。在本研究中,TCZ 在严重或危重新冠病毒肺炎患者中的非标签使用取得了良好效果。

TCZ 在 COVID-19 肺炎重症和危重症患者中的非标签使用对管理“细胞因子风暴”有效。在年轻患者中,结果更好。联合使用辅助铁螯合剂可能有助于改善预后,需要在更大规模的研究中进一步证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67c8/8104262/416709ceaa00/medi-100-e25832-g001.jpg

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