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COVID-19 患者在出现血清转换之前使用门诊获得的 COVID-19 恢复期血浆。

Use of Outpatient-Derived COVID-19 Convalescent Plasma in COVID-19 Patients Before Seroconversion.

机构信息

Department of Pathology, Stanford University School of Medicine, Stanford, CA, United States.

Stanford Blood Center, Palo Alto, CA, United States.

出版信息

Front Immunol. 2021 Sep 14;12:739037. doi: 10.3389/fimmu.2021.739037. eCollection 2021.

Abstract

BACKGROUND

Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients.

METHODS

Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients.

RESULTS

Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients.

CONCLUSION

Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.

摘要

背景

输注含有高滴度抗 SARS-CoV-2 抗体的 COVID-19 恢复期血浆(CCP)可作为 COVID-19 患者的治疗方法。在疾病早期进行输血被证明是有益的。SARS-CoV-2 大流行的经验教训可以为应对未来的大流行提供早期信息,并可能继续在资源较少的环境中具有相关性。我们试图确定与恢复期血浆供体高抗体滴度相关的因素,并了解输注抗体滴度和输注受体内源性抗体滴度的幅度和药代动力学时间过程。

方法

从 93 名轻症 COVID-19 恢复期血浆供体和 16 名 COVID-19 患者中收集恢复期后 174 天内的血浆样本。使用 ELISA 检测 SARS-CoV-2 刺突 RBD、S1 和 N 蛋白抗体,以及抗体阻断 ACE2 与 RBD 结合的能力。作为病毒载量的估计,在 COVID-19 患者中评估病毒 RNA 和 N 蛋白的血浆水平。

结果

抗 SARS-CoV-2 抗体水平和 RBD-ACE2 阻断能力在症状缓解后 60 天内最高,并在 120 天后显著下降。在经历发热的 CCP 供体中发现最高的抗体滴度。在接受高滴度 CCP 且在输血时尚未发生血清转化的 COVID-19 患者中,可以检测到输注 CCP 的效果。其中两名患者的病毒 RNA 减少。

结论

我们的结果表明,应在从过去有发热史的供体中康复后 60 天内采集高滴度 CCP。与患者体内内源性产生的抗体相比,输注抗体的滴度要低得多,这突出表明在发生内源性血清转化之前提供 CCP 的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f046/8477649/5046ebbffd38/fimmu-12-739037-g001.jpg

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