Tillmann Frank-Peter, Figiel Lars, Ricken Johannes, Still Hermann, Korte Christoph, Plaßmann Grete, Harth Ana, Jörres Achim, von Landenberg Philipp
Department of Medicine I-Nephrology, Transplantation & Medical Intensive Care, Medical Center Cologne-Merheim, University Witten/Herdecke, Ostmerheimer Str. 200, D-51109 Cologne, Germany.
Nephrologisches Zentrum Ibbenbüren, Gravenhorsterstr. 1, D-49477 Ibbenbüren, Germany.
J Clin Med. 2022 Jun 2;11(11):3187. doi: 10.3390/jcm11113187.
The aim of this study is to determine the effect of repeated vaccinations on neutralizing SARS-CoV-2 IgG antibody titers, evaluate risk factors for immunological non-response, and to report breakthrough infections in chronic hemodialysis patients.
A prospective, multi-center cohort study in 163 chronic hemodialysis patients was conducted. Antibody titers were measured three months after second, third, and fourth (10 pts) booster vaccinations. SARS-CoV-2 neutralizing antibody titers in BAU/mL and % inhibition were divided into three categories (<216, 216-433, >433 and <33, 33-66, and >66%). Somers's test, paired t-test, and univariable and multivariable logistic regression analysis were applied to evaluate differences in antibody levels and search for risk factors for vaccination failure defined as neutralizing titers <50% and/or need for repeated booster vaccinations. Furthermore, we report on a case series to describe characteristics of patients after four vaccinations ( = 10) and breakthrough infections ( = 20).
Third dose boosters resulted in higher proportions of patients with neutralizing antibody levels >66% as compared to after the second dose (64.7% after second dose vs. 88.9% after third dose, = 0.003), as well as in a respective increase in neutralizing titer levels in % from 68 ± 33% to 89 ± 24 ( <0.001). The proportion of patients with IgG-titers below 216 BAU/mL decreased from 38.6 to 10.5% ( ≤ 0.001). Age ( = 0.004, OR 1.066, 95% CI 1.020-1.114) and presence of immunosuppressive medications ( = 0.002, OR 8.267, 95% CI 2.206-30.975) were identified as major risk factors for vaccination failure. Repeated booster vaccinations ≥4 times were effective in 8 out of 10 former low-responders (80%) without any side effects or safety concerns. Breakthrough infections showed a clinically mild course but were associated with prolonged viral shedding on PCR-testing ranging 7-29 (mean 13) days.
Third and fourth mRNA-based booster vaccinations resulted in higher and longer lasting SARS-CoV-2 antibody levels as compared to after two dosages. The presence of immunosuppressive medication and repeat vaccinations are major potentially modifiable measures to increase antibody levels in non-or low-responders. Breakthrough infections with SARS-CoV-2 Omicron were associated with prolonged viral shedding but clinically mild disease courses.
本研究的目的是确定重复接种疫苗对中和新型冠状病毒2型IgG抗体滴度的影响，评估免疫无反应的风险因素，并报告慢性血液透析患者的突破性感染情况。
对163例慢性血液透析患者进行了一项前瞻性、多中心队列研究。在第二次、第三次和第四次（10例）加强接种疫苗三个月后测量抗体滴度。将以BAU/mL为单位的新型冠状病毒2型中和抗体滴度和抑制百分比分为三类（<216、216 - 433、>433和<33、33 - 66以及>66%）。应用Somers检验、配对t检验以及单变量和多变量逻辑回归分析来评估抗体水平的差异，并寻找定义为中和滴度<50%和/或需要重复加强接种疫苗的接种失败风险因素。此外，我们报告了一个病例系列，以描述四次接种疫苗后（n = 10）和突破性感染患者（n = 20）的特征。
与第二次接种后相比，第三次加强接种后中和抗体水平>66%的患者比例更高（第二次接种后为64.7%，第三次接种后为88.9%，P = 0.003），并且中和滴度水平相应从68±33%提高到89±24%（P<0.001）。IgG滴度低于216 BAU/mL的患者比例从38.6%降至10.5%（P≤0.001）。年龄（P = 0.004，OR 1.066，95%CI 1.020 - 1.114）和使用免疫抑制药物（P = 0.002，OR 8.267，95%CI 2.206 - 30.975）被确定为接种失败的主要风险因素。10例既往低反应者中有8例（80%）在重复加强接种≥4次后有效，且无任何副作用或安全问题。突破性感染的临床过程较轻，但在PCR检测中病毒脱落时间延长，为7 - 29天（平均13天）。
与两次接种相比，第三次和第四次基于mRNA的加强接种导致更高且更持久的新型冠状病毒2型抗体水平。使用免疫抑制药物和重复接种是增加无反应或低反应者抗体水平的主要潜在可改变措施。新型冠状病毒奥密克戎变异株的突破性感染与病毒脱落时间延长有关，但临床病程较轻。
