Relevant concerns are being raised regarding the weak serological response of solid organ transplant (SOT) recipients after receiving two doses of messenger RNA-based vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)¹ and some severe cases of coronavirus disease (COVID-19) occurring after vaccination.² Thus, additional preventive booster doses are proposed to enhance anti-viral immunity.^{3, 4}

In this regard, recent reports have shown the immunological response to a third dose of the two main mRNA-based vaccines (BNT162b2; Pfizer–BioNTech or mRNA-1273; Moderna) leading to an increase in IgG seroconversion rates from 40% to 50%–70% 4 weeks after, especially among those with detectable antibodies after the two doses. Despite that no SARS-CoV-2 infections occurred, these data suggest the need of booster doses in this particularly vulnerable patient population. Nevertheless, while this evidence points toward an impaired adaptive immune response to vaccination in SOT patients,⁵ the short-term clinical scenario of the incidence of COVID-19 among SOT after two vaccine doses does not fully support this biological feature.

To investigate this question, we took advantage of the rapid vaccine prioritization of SOT patients in our country, which was done over a 3-week period starting late February 2021, and by early May, up to 90% of the total SOT population had received the two doses (http://trasplantaments.gencat.cat).

Remarkably, in our SOT center (the largest in Spain [http://www.ont.es/infesp/Paginas/Memorias.aspx]), the incidence of SARS-CoV-2 infection markedly dropped during the 4 months after vaccination (March–June) (Figure 1, Table S1). Out of the total 117 detected infections over this 8-month period, 103 (88%) occurred before and only 14 (12%) after vaccination occurring 6/14 (42.8%) infections between the first and second dose. This difference was observed across all types of SOT and remained significant in a multivariate Poisson model accounting for age, gender, and type of SOT and immunosuppression (incidence ratio [IR] 0.211, p < .001) (Figure S2). To assess the independent effect of the two-dose vaccination, we compared COVID-19 rates between SOT and the general population in our region (www.dadescovid.cat) using a Poisson regression model analyzing the influence of the investigation period on COVID-19 incidences. Interestingly, the effect of vaccination era (before/after) had a significant impact on IRs of vaccination (0.50, p < .001) (Table S2), independently of the progressive reduction of infection rates observed over the same time period in the general population (Figure S1). Notably, the same adjusted incidences of patients requiring hospitalization, ICU admission, and deaths related to COVID-19 significantly decreased after vaccination (Table S2). Therefore, we did not make any recommendation for further vaccine booster aimed at improving this initial protection during this initial timeframe.

Interestingly, the reduction in COVID-19 infections, did also overlap with less restrictive community measures and a marked reduction of virus circulation, thus suggesting on the one hand a progressive generation of herd immunity (due to a widespread vaccination policy) and less viral infectivity, and on the other, the relative role of other protective immunological mechanisms such as virus-specific cellular immunity controlling viral replication. Altogether, while generalized booster vaccinations seem to be likely necessary among SOT in view of the low seroconversion rates, especially with the now-predominant Delta variant, the question is whether a vaccine should treat numbers or improve clinical outcomes, thus a better immune-risk stratification of SOT patients and the development of interventional clinical trials aiming at conferring immune protection, also involving these biomarkers, is highly warranted.

^{人们对实体器官移植 (SOT) 接受者在接受两剂针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 1}和一些严重冠状病毒病例的基于信使 RNA 的疫苗后的血清学反应较弱提出了相关担忧接种疫苗后发生的疾病 (COVID-19)。²因此，建议额外注射预防性加强剂以增强抗病毒免疫力。^{3, 4}

在这方面，最近的报告显示，对两种主要基于 mRNA 的疫苗（BNT162b2；Pfizer–BioNTech 或 mRNA-1273；Moderna）的第三剂免疫反应导致 IgG 血清转化率从 40% 增加到 50% –70% 4 周后，特别是在两次剂量后具有可检测抗体的人群中。尽管没有发生 SARS-CoV-2 感染，但这些数据表明在这个特别脆弱的患者群体中需要加强剂量。然而，尽管这一证据表明 SOT 患者对疫苗接种的适应性免疫反应受损，⁵但两次疫苗接种后 SOT 中 COVID-19 发病率的短期临床情景并不完全支持这一生物学特征。

为了调查这个问题，我们利用了我国 SOT 患者的快速疫苗优先次序，这是从 2021 年 2 月下旬开始的 3 周时间内完成的，到 5 月初，高达 90% 的 SOT 患者接种了疫苗两剂 (http://trasplantaments.gencat.cat)。

值得注意的是，在我们的 SOT 中心（西班牙最大的 [http://www.ont.es/infesp/Paginas/Memorias.aspx]），SARS-CoV-2 感染的发生率在接种疫苗后的 4 个月内显着下降（三月至六月）（图 1，表 S1）。在这 8 个月期间检测到的 117 例感染中，103 例 (88%) 发生在接种疫苗之前，只有 14 例 (12%) 发生在接种疫苗后，6/14 (42.8%) 例感染发生在第一剂和第二剂之间。在所有类型的 SOT 中都观察到这种差异，并且在考虑年龄、性别和 SOT 类型和免疫抑制的多变量泊松模型中仍然显着（发生率 [IR] 0.211，p < .001)（图 S2）。为了评估两剂疫苗接种的独立效果，我们使用泊松回归模型比较了 SOT 和我们地区一般人群 (www.dadescovid.cat) 的 COVID-19 发生率，该模型分析了调查期对 COVID-19 的影响事件。有趣的是，疫苗接种时代（之前/之后）的影响对疫苗接种的 IR 有显着影响（0.50，p < .001)（表 S2），独立于在同一时间段内观察到的一般人群中感染率的逐渐降低（图 S1）。值得注意的是，接种疫苗后，与 COVID-19 相关的需要住院、入住 ICU 和死亡的患者的相同调整后发生率显着降低（表 S2）。因此，我们没有就旨在在此初始时间范围内改善此初始保护的进一步疫苗加强剂提出任何建议。

有趣的是，COVID-19 感染的减少确实也与限制性较低的社区措施和病毒传播的显着减少重叠，因此一方面表明群体免疫力的逐步产生（由于广泛的疫苗接种政策）和较低的病毒传染性，另一方面，其他保护性免疫机制的相对作用，例如控制病毒复制的病毒特异性细胞免疫。总而言之，鉴于低血清转化率，尤其是现在占主导地位的 Delta 变体，在 SOT 中似乎有必要进行普遍的加强疫苗接种，但问题是疫苗是否应该治疗数量或改善临床结果，