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肾移植受者和透析患者接种三剂新冠病毒病(COVID-19)初级疫苗后的血清学反应及临床结果

Serological responses and clinical outcomes following a three-dose primary COVID-19 vaccine schedule in kidney transplant recipients and people on dialysis.

作者信息

Tharmaraj Dhakshayini, Boo Irene, O'Hara Jessie, Sun Shir, Polkinghorne Kevan R, Dendle Claire, Turner Stephen J, van Zelm Menno C, Drummer Heidi E, Khoury Gabriela, Mulley William R

机构信息

Department of Nephrology Monash Health Clayton VIC Australia.

Department of Medicine, Centre for Inflammatory Diseases Monash University Melbourne VIC Australia.

出版信息

Clin Transl Immunology. 2024 Jul 25;13(7):e1523. doi: 10.1002/cti2.1523. eCollection 2024.

Abstract

OBJECTIVES

Despite vaccination strategies, people with chronic kidney disease, particularly kidney transplant recipients (KTRs), remained at high risk of poor COVID-19 outcomes. We assessed serological responses to the three-dose COVID-19 vaccine schedule in KTRs and people on dialysis, as well as seroresponse predictors and the relationship between responses and breakthrough infection.

METHODS

Plasma from 30 KTRs and 17 people receiving dialysis was tested for anti-Spike receptor binding domain (RBD) IgG and neutralising antibodies (NAb) to the ancestral and Omicron BA.2 variant after Doses 2 and 3 of vaccination.

RESULTS

After three doses, KTRs achieved lower anti-Spike RBD IgG levels ( < 0.001) and NAb titres than people receiving dialysis ( = 0.002). Seropositive cross-reactive Omicron neutralisation levels were achieved in 11/27 (40.7%) KTRs and 11/14 (78.6%) dialysis recipients. ChAdOx1/viral-vector vaccine type, higher mycophenolate dose (> 1 g per day) and lower absolute B-cell counts predicted poor serological responses in KTRs. ChAdOx-1 vaccine type and higher monocyte counts were negative predictors in dialysis recipients. Among ancestral NAb seroresponders, higher NAb levels positively correlated with higher Omicron neutralisation ( = 0.9,  < 0.001). More KTRs contracted SARS-CoV-2 infection (14/30; 47%) than dialysis recipients (5/17; 29%) and had more severe disease. Those with breakthrough infections had significantly lower median interdose incremental change in anti-Spike RBD IgG and ancestral NAb titres.

CONCLUSION

Serological responses to COVID-19 vaccines in KTRs lag behind their dialysis counterparts. KTRs remained at high risk of breakthrough infection after their primary vaccination schedule underlining their need for booster doses, strict infection prevention measures and close surveillance.

摘要

目的

尽管采取了疫苗接种策略,但慢性肾脏病患者,尤其是肾移植受者(KTRs),感染新冠病毒(COVID-19)后出现不良结局的风险仍然很高。我们评估了KTRs和透析患者对三剂COVID-19疫苗接种方案的血清学反应、血清反应预测因素以及反应与突破性感染之间的关系。

方法

在接种第2剂和第3剂疫苗后,检测了30名KTRs和17名接受透析患者的血浆中针对原始毒株和奥密克戎BA.2变体的抗刺突受体结合域(RBD)IgG和中和抗体(NAb)。

结果

三剂接种后,KTRs的抗刺突RBD IgG水平(<0.001)和NAb滴度低于接受透析的患者(=0.002)。11/27(40.7%)的KTRs和11/14(78.6%)的透析患者达到了血清反应阳性的交叉反应性奥密克戎中和水平。ChAdOx1/病毒载体疫苗类型、更高的霉酚酸剂量(>1克/天)和更低的绝对B细胞计数预示着KTRs的血清学反应较差。ChAdOx-1疫苗类型和更高的单核细胞计数是透析患者血清反应的阴性预测因素。在原始毒株NAb血清反应者中,更高的NAb水平与更高的奥密克戎中和水平呈正相关(=0.9,<0.001)。感染SARS-CoV-2的KTRs(14/30;47%)比透析患者(5/17;29%)更多,且病情更严重。发生突破性感染的患者,其抗刺突RBD IgG和原始毒株NAb滴度的剂量间期增量变化中位数显著更低。

结论

KTRs对COVID-19疫苗的血清学反应落后于透析患者。KTRs在完成基础疫苗接种方案后仍有较高的突破性感染风险,这突出了他们需要加强剂量、严格的感染预防措施和密切监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e056/11272417/835939aa6635/CTI2-13-e1523-g003.jpg

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