Pharmacokinetics of high-titer anti-SARS-CoV-2 human convalescent plasma in high-risk children.
Pharmacokinetics of high-titer anti-SARS-CoV-2 human convalescent plasma in high-risk children.
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DOI：
10.1172/jci.insight.151518
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发表时间：
2022-01-25
期刊：
影响因子：
8
通讯作者：
Jain SK
中科院分区：
文献类型：
--
作者：
Gordon O;Brosnan MK;Yoon S;Jung D;Littlefield K;Ganesan A;Caputo CA;Li M;Morgenlander WR;Henson SN;Ordonez AA;De Jesus P;Tucker EW;Peart Akindele N;Ma Z;Wilson J;Ruiz-Bedoya CA;Younger MEM;Bloch EM;Shoham S;Sullivan D;Tobian AA;Cooke KR;Larman B;Gobburu JV;Casadevall A;Pekosz A;Lederman HM;Klein SL;Jain SK
虽然大多数感染 COVID-19 的儿童病情较轻，但患有基础疾病的高危儿童可能会发展为严重疾病，需要干预。疾病早期通过 COVID-19 恢复期血浆转移的抗体动力学尚未得到表征。在这项研究中，高危儿童前瞻性地入组接受高滴度的 COVID-19 恢复期血浆（>1:320 抗尖峰 IgG；Euroimmun）。输血后长达 2 个月的时间内对抗体的被动转移和内源性抗体的产生进行了连续评估。进行了商业和研究 ELISA 测定、病毒中和测定、利用冠状病毒表位库的高通量噬菌体展示测定以及药代动力学分析。 14 名高危儿童（中位年龄为 7.5 岁）接受了高滴度的 COVID-19 恢复期血浆，其中 9 名儿童在症状出现后 5 天内（范围为 2-7 天），5 名儿童在接触 SARS-CoV-2 后 4 天内（范围为 3-5 天）接受了治疗。没有发生与输血相关的严重不良事件。针对 SARS-CoV-2 的抗体从供体转移至受体，但抗体滴度下降了 14-21 天，刺突蛋白 IgG 的半衰期为 15.1 天。供体血浆具有显着的中和能力，可被转移到受体体内。然而，早在输血后 30 分钟，受者血浆中和滴度就为供者滴度的 6.2%（范围为 5.9%–6.7%）。将恢复期血浆输注给高危儿童似乎是安全的，无论体重或年龄如何，都具有预期的抗体动力学。然而，目前在高危儿童中使用恢复期血浆已达到中和能力，这可以预防严重疾病，但不太可能提供持久的保护。 ClinicalTrials.gov NCT04377672。马里兰州、彭博慈善基金会和 NIH（拨款 R01-AI153349、R01-AI145435-A1、K08-AI139371-A1 和 T32-AI052071）。
While most children who contract COVID-19 experience mild disease, high-risk children with underlying conditions may develop severe disease, requiring interventions. Kinetics of antibodies transferred via COVID-19 convalescent plasma early in disease have not been characterized. In this study, high-risk children were prospectively enrolled to receive high-titer COVID-19 convalescent plasma (>1:320 anti-spike IgG; Euroimmun). Passive transfer of antibodies and endogenous antibody production were serially evaluated for up to 2 months after transfusion. Commercial and research ELISA assays, virus neutralization assays, high-throughput phage-display assay utilizing a coronavirus epitope library, and pharmacokinetic analyses were performed. Fourteen high-risk children (median age, 7.5 years) received high-titer COVID-19 convalescent plasma, 9 children within 5 days (range, 2–7 days) of symptom onset and 5 children within 4 days (range, 3–5 days) after exposure to SARS-CoV-2. There were no serious adverse events related to transfusion. Antibodies against SARS-CoV-2 were transferred from the donor to the recipient, but antibody titers declined by 14–21 days, with a 15.1-day half-life for spike protein IgG. Donor plasma had significant neutralization capacity, which was transferred to the recipient. However, as early as 30 minutes after transfusion, recipient plasma neutralization titers were 6.2% (range, 5.9%–6.7%) of donor titers. Convalescent plasma transfused to high-risk children appears to be safe, with expected antibody kinetics, regardless of weight or age. However, current use of convalescent plasma in high-risk children achieves neutralizing capacity, which may protect against severe disease but is unlikely to provide lasting protection. ClinicalTrials.gov NCT04377672. The state of Maryland, Bloomberg Philanthropies, and the NIH (grants R01-AI153349, R01-AI145435-A1, K08-AI139371-A1, and T32-AI052071).
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影响因子：
7.5
作者：
Rodriguez Z;Shane AL;Verkerke H;Lough C;Zimmerman MG;Suthar M;Wrammert J;MacDonald H;Wolf M;Clarke S;Roback JD;Arthur CM;Stowell SR;Josephson CD
通讯作者：
Josephson CD
DOI：
10.1007/s10096-004-1271-9
发表时间：
2005-01
期刊：
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
影响因子：
--
作者：
Cheng Y;Wong R;Soo YO;Wong WS;Lee CK;Ng MH;Chan P;Wong KC;Leung CB;Cheng G
通讯作者：
Cheng G
影响因子：
36.4
作者：
Goetzinger, Florian;Santiago-Garcia, Begona;Tebruegge, Marc
通讯作者：
Tebruegge, Marc
影响因子：
3.4
作者：
Klein MN;Wang EW;Zimand P;Beauchamp H;Donis C;Ward MD;Martinez-Hernandez A;Tabatabai A;Baddley JW;Bloch EM;Mullins KE;Fontaine MJ
通讯作者：
Fontaine MJ
DOI：
10.1093/jpids/piaa165
发表时间：
2021-05-01
影响因子：
3.2
作者：
Hopwood, Andrew J.;Jordan-Villegas, Alejandro;Laham, Federico R.
通讯作者：
Laham, Federico R.