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体液免疫反应和 COVID-19 mRNA 疫苗接种后儿童和青少年慢性肾脏病患者对 SARS-CoV-2 奥密克戎(BA.1)变异株的活病毒中和作用。

Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease.

机构信息

Department of Pediatrics I, University Children's Hospital Heidelberg, Heidelberg, Germany.

Institute of Virology, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany.

出版信息

Pediatr Nephrol. 2023 Jun;38(6):1935-1948. doi: 10.1007/s00467-022-05806-9. Epub 2022 Nov 21.

Abstract

BACKGROUND

Data on humoral immune response to standard COVID-19 vaccination are scarce in adolescent patients and lacking for children below 12 years of age with chronic kidney disease including kidney transplant recipients.

METHODS

We therefore investigated in this retrospective two-center study (DRKS00024668; registered 23.03.2021) the humoral immune response to a standard two-dose mRNA vaccine regimen in 123 CKD patients aged 5-30 years. A live-virus assay was used to assess the serum neutralizing activity against the SARS-CoV-2 omicron (BA.1) variant.

RESULTS

Children aged 5-11 years had a comparable rate and degree of immune response to adolescents despite lower vaccine doses (10 µg vs. 30 µg BNT162b2). Treatment with two (odds ratio 9.24) or three or more (odds ratio 17.07) immunosuppressants was an independent risk factor for nonresponse. The immune response differed significantly among three patient cohorts: 48 of 77 (62.3%) kidney transplant recipients, 21 of 26 (80.8%) patients on immunosuppressive therapy, and 19 of 20 (95.0%) patients with chronic kidney disease without immunosuppressive therapy responded. In the kidney transplant recipients, immunosuppressive regimens comprising mycophenolate mofetil, an eGFR of < 60 mL/min/1.73 m, and female sex were independent risk factors for nonresponse. Two of 18 (11.1%) and 8 of 16 (50.0%) patients with an anti-S1-RBD IgG of 100-1411 and > 1411 BAU/mL, respectively, showed a neutralization activity against the omicron variant.

CONCLUSION

A standard mRNA vaccine regimen in immunosuppressed children and adolescents with kidney disease elicits an attenuated humoral immune response with effective live virus neutralization against the omicron variant in approximately 10% of the patients, underlying the need for omicron-adapted vaccination. A higher resolution version of the Graphical abstract is available as Supplementary information.

摘要

背景

关于标准 COVID-19 疫苗接种对青少年患者的体液免疫反应的数据很少,对于包括肾移植受者在内的 12 岁以下患有慢性肾脏病的儿童则缺乏此类数据。

方法

因此,我们在这项回顾性的双中心研究(DRKS00024668;于 2021 年 3 月 23 日注册)中调查了 123 例年龄在 5-30 岁的慢性肾脏病患者对标准两剂 mRNA 疫苗方案的体液免疫反应。使用活病毒测定法评估针对 SARS-CoV-2 奥密克戎(BA.1)变体的血清中和活性。

结果

尽管儿童的疫苗剂量较低(10μg 比 30μg BNT162b2),但 5-11 岁的儿童与青少年相比,其免疫反应的速度和程度相当。使用两种(优势比 9.24)或三种或更多种(优势比 17.07)免疫抑制剂治疗是无反应的独立危险因素。三个患者队列之间的免疫反应存在显著差异:77 例肾移植受者中有 48 例(62.3%),26 例中有 21 例(80.8%)接受免疫抑制治疗的患者和 20 例中有 19 例(95.0%)无免疫抑制治疗的慢性肾脏病患者有反应。在肾移植受者中,包含霉酚酸酯、eGFR<60 mL/min/1.73 m2 和女性的免疫抑制方案是无反应的独立危险因素。18 例中有 2 例(11.1%)和 16 例中有 8 例(50.0%)的抗 S1-RBD IgG 分别为 100-1411 和>1411 BAU/mL 的患者对奥密克戎变异体具有中和活性。

结论

在患有肾脏疾病的免疫抑制儿童和青少年中,标准的 mRNA 疫苗方案会引起较弱的体液免疫反应,对奥密克戎变异体有有效的活病毒中和作用,约 10%的患者需要适应奥密克戎的疫苗接种。图表摘要的更高分辨率版本可在补充信息中获得。

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