Purpose: Evaluate long-term immunogenicity and its association with the number of vaccines and breakthrough infections in patients with hematologic malignancies compared to a healthy cohort.Methods: This study is an amendment of a multicenter study (DRKS00027372) which described the upsurge of anti-spike-IgGs on day 120 from a blunted day-35 response in patients with hematologic neoplasms. In this amendment, 191 individuals from the original study (patients with myeloid and lymphoid neoplasms and controls) were followed beyond month 12 after first SARS-CoV-2-vaccination. The long-term humoral and cellular responses and their correlation with the number of vaccines were studied.Results: After a median follow-up of 18 months, a median of three vaccinations (range 1–5) were given. Antibody levels did not correlate with the number of vaccinations (≤2 versus ≥3) (p= 0.3). With a median of 5274 U/mL anti-spike-IgGs, the inferior day-120 antibody response in patients with lymphoid neoplasms was no longer detected. Breakthrough SARS-CoV-2-infections, mostly mild, occurred in 67% of controls and 46% of patients. Patients with lymphoid neoplasms with two vaccinations did not have more infections compared to patients with more doses (p= 0.4). There was a significant decline in the spike-specific T-cell response for CovCD4+and CovCD8+(p< 0.001). On last assessment, 33% of individuals lost their day-120 CovCD4+-positive response (p< 0.001). There was no correlation between the number of vaccinations and cellular immune response in patients and controls (p= 0.3).Conclusions: In this study, breakthrough infections were high despite repeated boosting, which by itself does not lead to an upsurge in the cellular immune response in the majority of patients.
目的:评估血液系统恶性肿瘤患者与健康人群相比的长期免疫原性,及其与疫苗接种次数和突破性感染的关系。 方法:本研究是一项多中心研究(DRKS00027372)的修正案,该研究描述了血液肿瘤患者在第35天反应减弱后,第120天抗刺突蛋白IgG抗体水平的上升。在此修正案中,对原始研究中的191名个体(包括髓系和淋巴系肿瘤患者及对照者)进行了首次SARS-CoV-2疫苗接种后12个月以上的随访。研究了长期体液和细胞免疫反应及其与疫苗接种次数的相关性。 结果:中位随访18个月后,受试者接受了中位数为3次(范围1-5次)的疫苗接种。抗体水平与疫苗接种次数(≤2次对比≥3次)无相关性(p=0.3)。淋巴瘤患者抗刺突蛋白IgG抗体中位水平为5274 U/mL,其第120天抗体反应较差的差异已不再显现。突破性SARS-CoV-2感染发生率在对照组为67%,患者组为46%,且多数为轻症。接受两次疫苗接种的淋巴瘤患者与接种更多剂次的患者相比,感染率并未更高(p=0.4)。刺突蛋白特异性T细胞反应(CovCD4+和CovCD8+)显著下降(p<0.001)。在末次评估时,33%的个体失去了第120天时的CovCD4+阳性反应(p<0.001)。患者和对照者的疫苗接种次数与细胞免疫反应之间无相关性(p=0.3)。 结论:在本研究中,尽管进行了重复加强免疫,突破性感染率仍然较高,且加强免疫本身并未导致大多数患者的细胞免疫反应增强。