We have read the article written by Ison et al.¹ that has raised some issues we would like to discuss. COVID-19 breakthrough infection rates in vaccinated kidney transplant (KT) recipients much higher than in the general vaccinated population have been reported.² Furthermore, the severity remains markedly high. Although Ison et al. referred cases are rarely severe, other series, and among them, the largest cohort published so far, have reported 27% of very serious cases.³

By August 2021, 843 KT recipients at our center have been fully vaccinated against COVID-19. During this period, 15 patients developed COVID-19 after two doses of mRNA-based vaccines: 1.8% versus 0.01% in the general population.² Of them, five needed hospitalization (33.3%): three remain in critical care units and one died. Contrary to what Ison et al. stated, also in our experience, severe COVID-19 has not been uncommon in infected vaccinated KT patients.

Although serological protective thresholds are not established yet, higher antibodies titers are associated with a less severe COVID-19 in the general population.⁴ We analyzed the response after two doses of mRNA-based vaccine in 97 randomly selected stable KT recipients (Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay). Six patients had COVID-19 previously; they all had detectable antibodies prior to vaccination, with a 20-fold increase 1 month after the second dose (201.8 vs. 3601.2 U/ml; p = .005). The rest of the patients were seronegative before the vaccine; in this group, the seroconversion rate was 62.6% 1 month after two vaccine doses. A shorter post-KT time, renal function, treatment with mycophenolic acid (MPA) and age were related to a lower response (Table 1). These last two factors have already been identified for a weak immune response.⁵ Thus, temporary withdrawal of MPA during the vaccination could be a strategy to increase the serological response in selected patients, although this needs to be carefully analyzed.

As in other series, these results have aroused interest in the administration of a booster dose in KT. The early data showed that, after this third dose, the seroconversion rate increased about 20% and there were no breakthrough infections during the follow-up.^{1, 5} Recently the Food and Drug Administration approved a third dose in immunocompromised population but most European countries, including Spain, have not yet made a decision.

Ison et al. presented their concern about the potential risk of acute rejection (AR) after the third dose of the vaccine. Notwithstanding, only one case has been reported,¹ so it is difficult to establish a causal association. The French study, with 396 solid organ transplant patients who received the third dose, did not observe any AR episode.⁵

In conclusion, we think that vaccination programs with a third dose should be fostered in KT recipients as long as we do not have more effective treatments or vaccines. A booster dose increases the response and it is unlikely to be associated with AR. Changes in immunosuppressive therapy could perhaps be proposed in some patients to improve the response to vaccine.

我们已经阅读了 Ison 等人撰写的文章。¹提出了一些我们想讨论的问题。据报道，接种疫苗的肾移植 (KT) 接受者的 COVID-19 突破性感染率远高于一般接种人群。²此外，严重程度仍然非常高。虽然 Ison 等人。提到的病例很少是严重的，其他系列，其中，迄今为止发表的最大队列，报告了 27% 的非常严重的病例。^3个

到 2021 年 8 月，我们中心的 843 名 KT 接受者已经完全接种了 COVID-19 疫苗。在此期间，有 15 名患者在接种两剂基于 mRNA 的疫苗后患上了 COVID-19：1.8% 对普通人群的 0.01%。²其中，5 人需要住院治疗 (33.3%)：3 人留在重症监护室，1 人死亡。与 Ison 等人相反。声明，同样根据我们的经验，严重的 COVID-19 在已接种疫苗的 KT 患者中并不少见。

尽管尚未确定血清学保护阈值，但较高的抗体滴度与一般人群中不太严重的 COVID-19 相关。⁴我们分析了 97 名随机选择的稳定 KT 接受者接种两剂基于 mRNA 的疫苗后的反应（雅培 SARS-CoV-2 IgG 化学发光微粒免疫测定）。六名患者之前患有 COVID-19；他们在接种疫苗前都有可检测到的抗体，在第二次接种后 1 个月增加了 20 倍（201.8 与 3601.2 U/ml；p =.005）。其余患者在接种疫苗前呈血清反应阴性；在该组中，两次疫苗接种后 1 个月的血清转化率为 62.6%。较短的 KT 后时间、肾功能、麦考酚酸 (MPA) 治疗和年龄与较低的反应相关（表 1）。最后两个因素已被确定为免疫反应较弱。⁵因此，在疫苗接种期间暂时停用 MPA 可能是增加选定患者血清学反应的一种策略，尽管这需要仔细分析。

与其他系列一样，这些结果引起了对 KT 加强剂量给药的兴趣。早期数据显示，在第三次接种后，血清转化率增加了约 20%，并且在随访期间没有出现突破性感染。^{1, 5}最近，美国食品和药物管理局批准了免疫功能低下人群的第三剂疫苗，但包括西班牙在内的大多数欧洲国家尚未做出决定。

伊森等人。表达了他们对第三剂疫苗后发生急性排斥反应 (AR) 的潜在风险的担忧。尽管如此，仅报告了一个病例¹ ，因此很难建立因果关系。法国的研究有 396 名接受第三剂的实体器官移植患者，没有观察到任何 AR 发作。^5个

总之，我们认为只要我们没有更有效的治疗方法或疫苗，就应该在 KT 接受者中培养第三剂疫苗接种计划。加强剂量会增加反应，并且不太可能与 AR 相关。或许可以建议某些患者改变免疫抑制疗法以改善对疫苗的反应。