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病例报告:恢复期血浆治疗后逐步出现抗炎和抗SARS-CoV-2作用并实现完全临床康复

Case Report: Stepwise Anti-Inflammatory and Anti-SARS-CoV-2 Effects Following Convalescent Plasma Therapy With Full Clinical Recovery.

作者信息

Zimmerli Aurelia, Monti Matteo, Fenwick Craig, Eckerle Isabella, Beigelman-Aubry Catherine, Pellaton Céline, Jaton Katia, Dumas Dominique, Stamm Gian-Marco, Infanti Laura, Andreu-Ullrich Heidrun, Germann Daphné, Mean Marie, Vollenweider Peter, Stadelmann Raphael, Prella Maura, Comte Denis, Guery Benoit, Gachoud David, Rufer Nathalie

机构信息

Department of Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Medical Education Unit, School of Medicine, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

出版信息

Front Immunol. 2021 Apr 21;12:613502. doi: 10.3389/fimmu.2021.613502. eCollection 2021.

Abstract

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients.

摘要

在新冠疫情期间,人们对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染对免疫功能低下患者的潜在影响表示关注,尤其是对那些接受B细胞耗竭剂治疗因而体液免疫反应严重受抑的患者。康复期血浆可作为这些患者的一种治疗选择。了解康复期血浆的潜在机制对于优化这种治疗方法至关重要。在此,我们描述了一名因利妥昔单抗(抗CD20单克隆抗体)及同时进行的化疗用于慢性淋巴细胞白血病而深度免疫抑制的新冠患者。他长期存在严重的T细胞和B细胞淋巴细胞减少,这使得我们能够评估康复期血浆的治疗效果。在临床、生物学和放射学层面监测治疗结果。此外,在血浆输注前后不同时间评估抗SARS-CoV-2抗体滴度(IgM、IgG和IgA)及中和活性,同时进行SARS-CoV-2 RNA定量分析及从上呼吸道进行病毒分离。在首次血浆输注周期后,患者的肺炎、炎症及血细胞计数迅速改善,这可能与血浆的免疫调节特性有关。随后,因另外三次血浆输注导致的抗SARS-CoV-2中和抗体的累积增加与病毒的逐步清除并最终完全清除相关,从而实现了完全的临床康复。在本病例报告中,康复期血浆的应用显示出一种逐步效应,即最初具有快速的抗炎活性,随后是SARS-CoV-2的逐步清除。这些数据对于康复期血浆及未来单克隆抗体在免疫抑制的新冠患者治疗中的更广泛应用具有潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7967/8097002/69bba72eae30/fimmu-12-613502-g001.jpg

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