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不同单克隆抗体治疗新型冠状病毒肺炎的不良反应及效用比较:一项回顾性队列研究

A Comparison of the Adverse Effects and Utility of Different Monoclonal Antibodies for SARS-CoV-2: A Retrospective Cohort Study.

作者信息

Knopp Brandon W, Weiss Hannah Z, Fahmy Samer, Goldstein Evan, Parmar Jeniel

机构信息

Department of Emergency Medicine, Florida Atlantic University Charles E. Schmidt College of Medicine, Boca Raton, USA.

Department of Emergency Medicine, Boca Raton Regional Hospital, Boca Raton, USA.

出版信息

Cureus. 2023 Aug 7;15(8):e43094. doi: 10.7759/cureus.43094. eCollection 2023 Aug.

Abstract

Introduction Multiple monoclonal antibody (mAb) treatments have been developed to combat the growing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. These treatments have been shown to be effective in reducing the risk of hospitalization and death from SARS-CoV-2 infection with a low risk of adverse effects; however, more data is required to evaluate the comparative efficacy of mAbs. The primary objective of this study is to describe the hospitalization rate, length of stay (LOS), and mortality rate in SARS-CoV-2 patients treated with four different mAb treatments, including bamlanivimab plus etesevimab, casirivimab plus imdevimab, sotrovimab, and bebtelovimab. Methods A retrospective chart review and prospective phone surveys of SARS-CoV-2 patients treated with mAbs in a 400-bed tertiary, suburban medical center were conducted between June 2020 and April 2022. Eligibility criteria for mAbs included non-hospitalized patients over the age of 18 with less than 10 days of SARS-CoV-2 symptoms and no oxygen requirement on emergency department (ED) admission. Data were collected from the retrospective chart review and subjective patient surveys. A chi-squared test was used. Significance was assessed at p < 0.05. Results The study population included 3249 patients, with 1537 males and 1712 females and an average age of 62.48 ± 17.54 years. Five hundred forty-two patients received bamlanivimab plus etesevimab; 849 received bebtelovimab; 1577 received casirivimab plus imdevimab; and 281 received sotrovimab. The overall hospitalization rate was 1.0%, and the mortality rate was 0.2% following mAb treatment. The hospitalization rate was greatest among patients administered Sotrovimab (2.1%) and least among patients administered Bebtelovimab (0.1%) (p = 0.010). 2.4% of patients who were discharged from the ED after receiving one of the four mAbs returned within 30 days with SARS-CoV-2 symptoms. The average length of stay was 4.75 ± 4.56 days, with no significant differences between the mAbs. The provider-reported adverse event rate was 2.2%, with significant differences in adverse event rates between mAbs. Bamlanivimab-etesevimab was associated with the highest adverse event rate (4.6%), and sotrovimab was associated with the lowest adverse event rate (1.4%) (p < 0.001). Conclusion This study shows a low hospitalization and mortality rate following mAb infusion in patients with mild and moderate COVID-19. However, there were significant differences in hospitalization and mortality among patients receiving each of the four mAb treatments. There was a high degree of patient-reported symptom improvement, and adverse reactions were reported in only 2.2% of patients with no severe reactions. Multiple monoclonal antibody treatments are not effective as monotherapy; however, this study shows the potential benefits of including a mAb infusion as part of a SARS-CoV-2 treatment plan.

摘要

引言 为应对不断增多的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)毒株,已研发出多种单克隆抗体(mAb)疗法。这些疗法已被证明可有效降低SARS-CoV-2感染导致的住院和死亡风险,且不良反应风险较低;然而,仍需要更多数据来评估单克隆抗体的比较疗效。本研究的主要目的是描述接受四种不同单克隆抗体疗法(包括巴瑞替尼单抗联合依替塞韦单抗、卡西瑞维单抗联合英德维单抗、索托维单抗和贝博泰洛维单抗)治疗的SARS-CoV-2患者的住院率、住院时长(LOS)和死亡率。

方法 于2020年6月至2022年4月期间,在一家拥有400张床位的郊区三级医疗中心,对接受单克隆抗体治疗的SARS-CoV-2患者进行回顾性病历审查和前瞻性电话调查。单克隆抗体的纳入标准包括年龄超过18岁、SARS-CoV-2症状出现少于10天且急诊科(ED)入院时无需吸氧的非住院患者。数据通过回顾性病历审查和患者主观调查收集。使用卡方检验。显著性评估的p值<0.05。

结果 研究人群包括3249例患者,其中男性1537例,女性1712例,平均年龄为62.48±17.54岁。542例患者接受巴瑞替尼单抗联合依替塞韦单抗治疗;849例接受贝博泰洛维单抗治疗;1577例接受卡西瑞维单抗联合英德维单抗治疗;281例接受索托维单抗治疗。单克隆抗体治疗后的总体住院率为1.0%,死亡率为0.2%。接受索托维单抗治疗的患者住院率最高(2.1%),接受贝博泰洛维单抗治疗的患者住院率最低(0.1%)(p = 0.010)。在接受四种单克隆抗体之一治疗后从急诊科出院的患者中,2.4%在30天内出现SARS-CoV-2症状后再次返回。平均住院时长为4.75±4.56天,各单克隆抗体之间无显著差异。医疗服务提供者报告的不良事件发生率为2.2%,各单克隆抗体的不良事件发生率存在显著差异。巴瑞替尼单抗-依替塞韦单抗的不良事件发生率最高(4.6%),索托维单抗的不良事件发生率最低(1.4%)(p < 0.001)。

结论 本研究表明,轻度和中度COVID-19患者接受单克隆抗体输注后的住院率和死亡率较低。然而,接受四种单克隆抗体治疗的患者在住院率和死亡率方面存在显著差异。患者报告的症状改善程度较高,仅2.2%的患者报告有不良反应,且无严重反应。多种单克隆抗体疗法作为单一疗法无效;然而,本研究显示了将单克隆抗体输注作为SARS-CoV-2治疗方案一部分的潜在益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7254/10482545/fb78b33c218e/cureus-0015-00000043094-i01.jpg

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