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因应全球新冠疫情的变化及疫苗研发进度，国际移植协会（TTS）感染分会（Transplant Infectious Disease，TID)《COVID-19移植临床医生工作指引》持续更新，最新版指引“TID COVID-19指导集中点评：移植受者SARS-COV-2疫苗接种”（TID COVID-19 GUIDANCE FOCUSED REVIEW: SARS-COV-2 VACCINES IN TRANSPLANT RECIPIENTS）于2021年8月20日更新。以下分享该章节相关要点内容及参考译文，仅供参考。
【要点（KEY POINTS）】
· Transplant recipients may be vaccinated with any of the authorized or approved COVID-19 vaccines.
移植受者可以接种任何经授权或批准的COVID-19疫苗。
· All transplant recipients should receive the vaccine, irrespective of past COVID-19 infection or positive SARS CoV-2 antibodies.
无论过去是否感染过COVID-19或SARS CoV-2抗体呈阳性，所有移植受者都应接种疫苗。
· For SOT recipients, the ideal timing of vaccination is uncertain in the post-transplantation setting.
1.Vaccination should be delayed at least one month after transplant surgery or rejection treatment.
2.Longer delays may be required for patients who have received anti-B (i.e. rituximab) or anti-T cell (anti-thymocyte globulin, alemtuzumab).
3.A risk-benefit assessment should weigh the community transmission risks against the likelihood of side effects.
对于实体器官移植（SOT）受者，在移植后接种疫苗的理想时间是不确定的。
1.移植手术或排斥治疗后应至少延迟1个月才能接种疫苗。
2.接受过抗B细胞（即利妥昔单抗）或抗T细胞（抗胸腺细胞球蛋白，阿仑单抗）的患者可能需要更长时间的延迟。
3.风险收益评估应权衡社区传播风险与副作用的可能性。
· For HSCT, in regions with accelerated transmission rates, COVID-19 vaccination may start at the 3rd month of HSCT. In regions where the risk of community acquisition of Covid-19 is lower, it is reasonable to wait until the sixth month after HSCT when better vaccine response is expected.
对于造血干细胞移植（HSCT）受者，在Covid-19传播速度加快的地区，疫苗接种可在移植后的第3个月开始。在社区感染风险较低的地区等到移植后第6个月接种，预计会有更好的疫苗反应。
· Organ donors who have received any COVID-19 vaccine may be used irrespective of time since vaccine; no vaccine would rule out a donor.
接种过任何COVID-19疫苗的供体，无论接种后多长时间都可以使用；不会因为是否接种疫苗而排除捐献者。
· SOT and HSCT candidates should also receive the COVID-19 vaccine.
1.The concomitant administration of COVID-19 vaccines with other vaccines is considered safe.
2.Organ offers for candidates who have been recently vaccinated or are between doses 1 and 2 should generally proceed to transplant. The persistence of protection has not been studied. Doses post-transplant should be delayed at least 1-month post-transplant.
SOT和HSCT的等待受者也应接种COVID-19疫苗。
1.COVID-19疫苗与其他疫苗同时使用被认为是安全的。
2.对于最近接种过疫苗或介于1剂和2剂之间的等待受者可以进行移植，但疫苗保护的持久性尚未研究。移植后应至少延迟1个月才能接种剩余剂量。
· Household contacts of transplant recipients should be vaccinated to improve ring protection of the recipient and reduce the risk of transmission within the household.
应为移植受者的家庭接触者接种疫苗，以提高对受者的保护并降低家庭内传播的风险。
· We do not recommend routine adjustment of immunosuppressive medications before vaccination.
不建议在接种疫苗前常规调整免疫抑制药物。
· We do not recommend checking antibody responses to the vaccine.
不建议检查对疫苗的抗体反应。
· We do recommend each center to develop approaches to educate patients on the importance of vaccination and consider tracking vaccination rates.
建议每个中心制定方法来教育患者疫苗接种的重要性，并考虑跟踪疫苗接种率。
· A third-dose booster of mRNA COVID-19 vaccine should be considered, where allowed by local regulatory approval. There is insufficient data to recommend boosters of patients who have not received mRNA vaccines at this time.
在当地监管部门批准的情况下，应考虑第三剂加强mRNA COVID-19疫苗。但目前仍没有足够的数据推荐未接种mRNA疫苗的患者加强免疫。
Transplant recipients who have received the COVID-19 vaccine should continue to observe all current preventive measures, such as masking, hand hygiene and safe distancing.
已接种COVID-19疫苗的移植受者应继续遵守所有当前的预防措施，例如戴口罩、保持手部卫生和保持安全距离。
【说明（INTRODUCTION）】
So far, 10 different platforms have been used in the development of these vaccines: 1) protein subunit (PS); 2) inactivated virus (IV); 3) non-replicating viral vector (VVnr); 4) RNA; 5) DNA; 6) virus-like particle (VLP); 7) replicating viral vector (VVr); 8) live attenuated virus (LAV); 9) VVnr + antigen-presenting cell (APC); and 10) VVr + APC.
迄今为止，已有10种不同的平台用于开发这些疫苗：1) 蛋白质亚基 (PS)；2) 灭活病毒 (IV)；3) 非复制型病毒载体（VVnr）；4) 核糖核酸；5) 脱氧核糖核酸；6）病毒样颗粒（VLP）；7）复制病毒载体（VVr）；8) 减毒活病毒 (LAV)；9) VVnr+抗原呈递细胞（APC）；和 10) VVr+APC。
To date, 21 SARS-CoV-2 vaccines have been authorized in several countries for emergency use (mRNA: Pfizer/ BioNTech, Moderna; Viral Vector: CanSino, Gamaleya Sputnik Light & Sputnik V, Janssen/Johnson & Johnson, AstraZeneca/Oxford, Serum Institute of India Covishield; DNA: Zydus Cadila; Inactivated: Sinopharm, Sinovac CoronaVac, Sinopharm (Wuhan), Chumakov Center KoviVac, Bharat Biotech Covaxin, Kazakhstan RIBSP QazVac, Minhai Biotechnology, Shifa Pharmed Industrial; Protein Subunit: FBRI EpiVacCorona, Center for Genetic Engineering and Biotechnology (CIGB), Anhui Zhifei Longcom RBD-Dimer). Vaccine role out has progressed considerably but continues to lag in low- and middle-income countries. In the healthy population, projected clinical efficacy based on phase 2 and phase 3 studies varies from more than 50% to 95%.1-9
迄今为止，已有21种SARS-CoV-2疫苗在多个国家获得批准用于紧急使用（mRNA：Pfizer/BioNTech、Moderna；病毒载体：CanSino、Gamaleya Sputnik Light & Sputnik V、Janssen/Johnson & Johnson、AstraZeneca/Oxford、印度 Covishield 血清研究所；DNA：Zydus Cadila；灭活：Sinopharm、Sinovac CoronaVac、Sinopharm（武汉）、Chumakov Center KoviVac、Bharat Biotech Covaxin、哈萨克斯坦 RIBSP QazVac、Minhai Biotechnology、Shifa Pharmed Industrial；蛋白质亚基：FBRI EpiVacCorona，中心基因工程与生物技术 (CIGB)，安徽智飞龙科 RBD-二聚体）。疫苗的应用取得了很大进展，但在低收入和中等收入国家仍然滞后。在健康人群中，基于2期和3期研究的预计临床疗效从50%以上到95%不等。［1-9］
Despite the achievements in such a short time, many questions remain unanswered, such as the titers of neutralizing antibodies for a COVID-19 vaccine to protect humans, the duration of vaccine-induced immunity, and the need for booster vaccines. These and other queries that may arise with the expanded use of the COVID-19 vaccines will likely be clarified over time.
尽管在如此短的时间内取得了成就，但许多问题仍未得到解答，例如保护人类的COVID-19疫苗的中和抗体滴度、疫苗诱导免疫的持续时间以及是否需要加强疫苗。随着COVID-19疫苗的扩大使用，一些问题可能会随着时间的推移而得到澄清。
COVID-19 vaccines in transplant recipients
移植受者的COVID-19疫苗
While prioritization of vaccines is generally determined by the federal, state and local health authorities, transplant recipients should be included in groups for earlier vaccination due to the risk for severe COVID-19. Immunocompromised patients, including transplant recipients, have not been included in studies performed to date. As these are not live virus vaccines, it is unlikely that these vaccines would pose additional risks. Transplant recipients may have decreased vaccine responses compared to the general population, and thus should be advised regarding the importance of maintaining all current guidance to protect themselves even after vaccination, including continuing to use masks, focus on hand hygiene and social distancing. Additionally, caregivers and household contacts should be strongly encouraged to get vaccinated when available to them to protect the patient.
虽然疫苗的优先顺序通常由联邦、州和地方卫生当局决定，但由于存在严重的COVID-19风险，移植受者应被纳入早期接种疫苗的群体。迄今为止进行的研究尚未包括免疫功能低下的患者，包括移植受者。由于这些不是活病毒疫苗，这些疫苗不太可能带来额外的风险。与一般人群相比，移植接受者的疫苗反应可能有所降低，因此应告知即使在接种疫苗后仍保持所有现行指导以保护自己的重要性，包括继续使用口罩、注重手部卫生和保持社交距离。此外，应大力鼓励护理人员和家庭接触者在有机会时接种疫苗，以保护移植受者。
Inactivated vaccines, protein subunit recombinant or virus-like vaccines are considered safe to be administered to transplant populations. Particle vaccines have been used for decades in transplant vaccination programs (e.g., influenza, hepatitis B and HPV vaccines). RNA vaccines (BioNTech/Pfizer, Moderna) and non-replicating viral vector vaccines (Oxford/AstraZeneca, Janssen/Johnson & Johnson, Gamaleya) are also considered safe vaccines, but have never been used in the transplant scenario. Vigilance will be necessary to determine if the induced protective immunity is not associated with an increased risk for rejection episodes or the development of graft versus host disease (GVHD).
灭活疫苗、蛋白质亚单位重组疫苗或病毒样疫苗被认为可以安全地用于移植人群。颗粒疫苗已在移植疫苗接种计划中使用了几十年（例如，流感、乙型肝炎和HPV疫苗）。RNA疫苗（BioNTech/Pfizer、Moderna）和非复制病毒载体疫苗（Oxford/AstraZeneca、Janssen/Johnson & Johnson、Gamaleya）也被认为是安全的疫苗，但从未用于移植实践。必须保持警惕，以确定诱导的保护性免疫是否与排斥事件或移植物抗宿主病 (GVHD) 的发展风险增加无关。
Preliminary data of 741 SOT recipients who received both doses of mRNA SARS-CoV-2 vaccine doses has recently provided early insight into the safety and efficacy of the mRNA vaccine in this population.10 Equal numbers of recipients received the Pfizer and Moderna vaccines and had low rates of local (84% after dose 1 and 77% after dose 2and systemic (overall: 49% after dose 1 and 69% after dose 2; fatigue 36% after dose 1 and 56% after dose 2; headache 28% after dose 1 and 42% after dose 2) reactions. Only 1 patient developed acute rejection following the second dose of vaccine.11-12
741名SOT受者的初步数据最近提供了对mRNA疫苗在该人群中的安全性和有效性的早期认识。[10] 同等数量的受者接种了辉瑞和Moderna疫苗，并且局部反应率较低（第1剂后为84%，第2剂后为77%和全身性（总体：第1剂后为49%，第2剂后为69%；注射后疲劳第1剂后为36%，第2剂后为56%；头痛第1剂后为28%，第2剂后为42%）。只有1名患者在第二剂疫苗后出现急性排斥反应。[11-12]
Unlike live virus vaccines, Adenovirus-vector vaccines have been genetically engineered to not replicate, and therefore cannot cause Adenovirus infection in the recipient. Based on the mechanism of action, expert opinion is that this vaccine is unlikely to trigger rejection episodes or have a novel or more severe side effects in transplant recipients, but more data are needed.
与活病毒疫苗不同，腺病毒载体疫苗经过基因工程改造，不会复制，因此不会在受者体内引起腺病毒感染。根据作用机制，专家意见认为这种疫苗不太可能引发排斥反应或对移植受者产生新的或更严重的副作用，但需要更多数据。
Live attenuated vaccines are generally contraindicated in SOT recipients and may be used with restrictions in HSCT recipients. Replicating viral vector vaccines are not recommended in transplant populations at this moment.
SOT受者通常禁用减毒活疫苗，但在HSCT受者中可能会有限制地使用。目前不建议在移植人群中使用复制病毒载体疫苗。
Several early studies have looked at the serologic response to the mRNA vaccines in SOT recipients. Detectable antibodies have been demonstrated to be relatively infrequent after the first dose but detectable in up to 54% of patients after both doses of the vaccine. When quantitative titers were available, they were frequently below the median titer in immunocompetent patients. However, the level of protective antibodies has not yet been defined. Furthermore, the protective components of both Cellular (T and NK T cells) and humoral responses (IgG/IgM or IgA) may not be linked in individual SOT recipients, and it is possible to still have an active acquired immune response in the absence of antibody and vice versa. In fact, 46% of patients with a negative anti-RBD can have a positive CD4+ T cell response 13. Hence, the rate of breakthrough and severity of breakthrough infections based on antibody or cellular response has not been fully studied to inform the clinical efficacy of the vaccine in the transplant population.11, 14-18
多项早期研究着眼于SOT受者对mRNA疫苗的血清学反应。已证明在第一剂疫苗后可检测到的抗体相对较少，但在接种两剂疫苗后可在多达54%的患者中检测到。当定量滴度可测时，它们通常低于免疫正常患者的中位滴度。然而，保护性抗体的水平尚未确定。此外，细胞（T和NKT细胞）和体液反应（IgG/IgM或IgA）的保护成分在个体SOT受者中可能没有联系，并且在没有抗体仍有可能产生活性的获得性免疫应答，反之亦然。事实上，46%的抗RBD阴性患者可以有阳性CD4+T细胞反应。[13]因此，基于抗体或细胞反应的突破率和突破感染的严重程度在移植人群的疫苗的临床疗效尚未完全研究清楚。11, 14-18
While there have been some observational cohort studies of transplant patients who have received a third dose of vaccine, either through government-approved channels or through other unapproved pathways, only one study to date has been a prospective, placebo-controlled study.13 In this trial, a third dose of vaccine was associated with a higher rate of patients having a pre-defined anti-RBD antibody level of at least 100 U per milliliter (33/60, 55% mRNA-1273 group vs. 10/57, 18% placebo), higher rate of neutralizing antibody titer and greater frequency of SARS-CoV-2 specific CD4+ T cell counts (432 vs. 67 cells per 106). There is no data yet on the impact of a third dose of vaccine on important clinical measures, including frequency and severity of COVID-19 of breakthrough infections. Likewise, it is important to note that 45% of patients failed to have a relevant antibody response even after 3 doses. Since seroprotective titers have yet to be established this may be an underestimate of the population still at risk for breakthrough infections. There is limited data on the utility of boosting with other vaccine times. While the larger studies suggest have demonstrated the safety of boosting with the same vaccine as the initial series, a recent study showed that BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S (transplant recipients were not included), induced a robust immune response with an acceptable and manageable reactogenicity profile.19
虽然通过政府批准的渠道或其他未经批准的途径对接受第三剂疫苗的移植患者进行了一些观察性队列研究，但迄今为止只有一项研究是前瞻性的安慰剂对照研究。[13] 在这项研究中在一项试验中，第三剂疫苗与预先定义的抗RBD抗体水平至少为100U/ml 的患者比例更高有关（33/60，55% mRNA-1273 组 vs. 10/57, 18 % 安慰剂）、更高的中和抗体滴度率和更高的SARS-CoV-2特异性CD4+T细胞计数频率（每10^6 个 432对67个细胞）。目前还没有关于第三剂疫苗对重要临床指标的影响的数据，包括COVID-19突破性感染的频率和严重程度。同样地，值得注意的是，45%的患者即使在3次给药后也未能产生相关的抗体反应。由于血清保护效价尚未确定，这可能低估了仍处于突破性感染风险中的人群。关于其他疫苗时间加强效用的数据有限。虽然更大规模的研究表明，使用与初始系列相同的疫苗加强免疫是安全的，但最近的一项研究表明，在接种了ChAdOx1-S（不包括移植受者）的个体中，作为第二剂给予BNT162b2具有可接受和可控的反应原性特征的免疫反应。由于血清保护效价尚未确定，这可能低估了仍处于突破性感染风险中的人群。关于其他疫苗时间加强效用的数据有限。虽然更大规模的研究表明，使用与初始系列相同的疫苗加强免疫是安全的，但最近的一项研究表明，在接种了ChAdOx1-S（不包括移植受者）的个体中，作为第二剂给予 BNT162b2具有可接受和可控的反应原性特征的免疫反应。[19]
Since humoral and cellular responses to vaccine, even with 3 doses, are reduced in immunocompromised patients, additional mitigation strategies should be continued post-vaccine and additional studies of alternative protective approaches are needed.
由于免疫功能低下患者对疫苗的体液和细胞反应也会降低，因此，即使接种3剂，在接种疫苗后应继续采取额外的缓解策略，并需要对替代保护方法进行额外研究。
There is emerging data on the benefit of the vaccine on transplant patients. The best data to date comes from the UK NHS Blood & Transplant group. In their retrospective review of registry data, 82% of English transplant recipients were fully vaccinated by July 9, 2021. Unadjusted data demonstrated a reduction in the frequency of breakthrough infections (3,473 in the unvaccinated vs. 143 in fully vaccinated) and case-fatality (438 deaths (12.6%) vs. 11 deaths (7.7%)) were lower in the vaccinated population.20 Similarly single-center clinical effectiveness data demonstrates an almost 80% reduction of symptomatic COVID-19 in vaccinated compared to unvaccinated SOT recipients.21
有关于疫苗对移植患者的益处，迄今为止最好的数据来自英国NHS血液和移植小组。在他们对注册数据的回顾性审查中，到2021年7月9日，82%的英国移植受者完全接种了疫苗。未经调整的数据表明，突破性感染的频率（未接种疫苗为3473，完全接种疫苗为143）和病死率有所降低[438例死亡（12.6%）与11例死亡（7.7%））]在接种人群中较低。[20] 同样的单中心临床有效性数据表明，与未接种疫苗的SOT受者相比，接种疫苗的有症状的COVID-19减少了近80%。[21]
There are still limited studies on the efficacy of vaccines against SARS-CoV-2 in HSCT. A recent study of 857 patients with hematological malignancies showed a lower median anti-S1 IgG antibody responses after two BNT162b2 vaccine doses in these patients than in healthcare workers of the same age group. Patients who are actively treated with BTKIs, ruxolitinib, venetoclax, or anti-CD20 antibody therapies seem to be the most negatively affected and might be left unprotected from SARS-CoV-2 infection. Surprisingly, patients who received autologous HSCT or allogeneic HSCT were among the subgroups with the highest responses to the SARS-CoV-2 vaccine, in comparison with other hematological patients.22
关于SARS-CoV-2疫苗在HSCT中的功效的研究仍然有限。最近一项针对857名血液系统恶性肿瘤患者的研究显示，这些患者在接种两次 BNT162b2疫苗后的抗S1 IgG抗体反应中位数低于同年龄组的医护人员。积极接受BTKI、鲁索替尼、venetoclax 或抗CD20抗体疗法治疗的患者似乎受到的负面影响最大，可能无法抵御SARS-CoV-2感染。令人惊讶的是，与其他血液病患者相比，接受自体造血干细胞移植或异基因造血干细胞移植的患者是对SARS-CoV-2疫苗反应最高的亚组。[22]
Given the existing data, it is essential that transplant programs provide education about the benefits and safety of the vaccine in transplant patients and strongly encourage vaccination. They should also remind patients that, given the limitations of vaccines in this population, even among patients who receive a third dose, they should continue to maintain the use of masks in public indoor spaces, maintain social distancing, and avoid high-risk exposures. Further, vaccination of close contact of our immunocompromised patients will reduce the risk of transmission of COVID-19 within a household.23
鉴于现有数据，移植计划必须提供有关疫苗对移植患者的益处和安全性的教育，并大力鼓励接种疫苗。他们还应提醒患者，鉴于该人群中疫苗的局限性，即使在接种第三剂的患者中，也应继续在公共室内空间使用口罩，保持社交距离，避免高风险暴露。此外，为免疫功能低下患者的密切接触者接种疫苗将降低COVID-19在家庭内传播的风险。[23]
参考文献 略
中文译文来自网页翻译，仅供参考，详细内容请查看原文链接：
https://tts.org/index.php?option=com_content&view=article&id=749&Itemid=140
https://tts.org/index.php?option=com_content&view=article&id=749&Itemid=140
【链接】
国际移植协会感染分会发布： 移植受者新冠疫苗接种指引
http://bbs.yizhiwang.org.cn/forum.php?mod=viewthread&tid=87349
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发表于 2021-9-3 22:47:07