肾移植受者接种新型冠状病毒疫苗的最新进展

肾移植受者由于长期服用免疫抑制药,免疫功能低下,感染新型冠状病毒后有更高的重症风险,对该高风险人群进行预防性接种疫苗至关重要。但有证据表明,肾移植受者对新型冠状病毒疫苗的免疫反应显著弱于健康人群,美国的标准接种方案如接种2针信使核糖核酸(mRNA)疫苗并不足以为肾移植受者提供足够的保护作用。已有多项研究证明增加肾移植受者疫苗接种的次数能够提高疫苗的效力,而调整免疫抑制治疗对提高疫苗效力的证据仍十分有限。本文就肾移植受者接种新型冠状病毒疫苗的重要性、有效性、特殊性以及免疫抑制治疗对新型冠状病毒疫苗效力影响进行综述,以期为肾移植受者的疫苗接种提供参考。     

中国肾移植受者新型冠状病毒疫苗接种与预防专家共识

目前, 新型冠状病毒感染已成为影响人类健康的重大公共卫生问题, 而接种疫苗是预防新型冠状病毒感染最有效的手段。因此, 在做好疫情常态化防控的同时, 加快新型冠状病毒疫苗接种的速度、扩大接种范围、提高人群的疫苗接种率, 已成为国际社会有效防控新型冠状病毒感染疫情的共识。肾移植受者是罹患新型冠状病毒感染的高危人群, 该群体长期处于低免疫状态, 因此存在新型冠状病毒疫苗免疫应答减弱、疫苗选择、使用方法、突破性感染等问题。本文基于已发表的国内外资料, 就肾移植受者新型冠状病毒疫苗接种与预防的有关问题提出建议并形成专家共识, 以供临床医生及卫生保健工作者参考。     

肾移植受者新型冠状病毒疫苗接种建议

目前, 新型冠状病毒感染已成为影响人类健康的重大公共卫生问题, 而接种疫苗是预防新型冠状病毒感染最有效的手段。因此, 在做好常态化疫情防控的同时, 加快新型冠状病毒疫苗接种速度、扩大接种范围、提高人群的疫苗接种率, 已成为国际社会有效防控新型冠状病毒感染疫情的共识。肾移植受者是罹患新型冠状病毒感染的高危人群, 该群体长期处于低免疫状态, 因此存在新型冠状病毒疫苗免疫原性降低、疫苗选择、使用方法、突破性感染等问题。本文基于已发表的国内外资料, 就肾移植受者接种新型冠状病毒疫苗的有关问题提出建议, 以供临床医生及卫生保健工作者提供咨询时参考。     

器官移植受者新型冠状病毒肺炎疫苗接种研究进展

本文就目前实体器官移植受者新型冠状病毒肺炎(COVID-19)疫苗接种的相关研究进行综述, 以期为移植受者COVID-19疫苗接种提供参考和建议。     

实体器官移植受者新型冠状病毒感染诊疗专家共识（2023年版）

自2019年底以来,新型冠状病毒（新冠病毒）感染大流行已席卷全球。虽然目前的新冠病毒变异株的致病性和毒力已较原始株有所下降,大多数患者预后良好,但实体器官移植（SOT）受者为新冠病毒感染脆弱人群,即使全程接种新冠病毒疫苗,SOT受者感染新冠病毒的住院或死亡风险依然较高。SOT受者新冠病毒感染后其临床表现、诊断和治疗均与普通人群存在很大的特殊性,需要高度关注。目前尚缺乏针对SOT受者可供参考的新冠病毒感染诊疗领域的指南或共识。因此,参考《新型冠状病毒感染诊疗方案（试行第十版）》及国内外文献,编写团队撰写了《实体器官移植受者新型冠状病毒感染诊疗专家共识（2023年版）》。本共识基于国内外新冠病毒感染的循证医学证据,并经过专家多次研讨达成一致意见后撰写成文,形成21条推荐意见,为SOT受者感染新冠病毒的诊疗提供参考。     

实体器官移植受者新型冠状病毒感染诊疗专家共识(2023年版)

自2019年底以来, 新型冠状病毒(新冠病毒)感染大流行已席卷全球。虽然目前的新冠病毒变异株的致病性和毒力已较原始株有所下降, 大多数患者预后良好, 但实体器官移植(SOT)受者人群为新冠病毒感染脆弱人群, 即使全程接种新冠病毒疫苗, SOT受者感染新冠病毒的住院或死亡风险依然较高。SOT受者新冠病毒感染后其临床表现、诊断和治疗均与普通人群存在很大的特殊性, 需要高度关注。目前尚缺乏针对SOT受者人群可供参考的新冠诊疗领域的指南或共识。因此, 参考《新型冠状病毒诊疗方案(试行第十版)》及国内外文献, 编写团队撰写了《实体器官移植受者新型冠状病毒感染诊疗专家共识(2023年版)》。本共识基于国内外新冠病毒感染的循证医学证据, 并经过专家多次研讨达成一致意见后撰写成文, 形成21条推荐意见, 为SOT受者感染新冠病毒的诊疗提供参考。     

肝移植术后受者接种新型冠状病毒灭活疫苗单中心回顾性研究

目的探讨肝移植受者术后接种新型冠状病毒灭活疫苗(以下简称新冠疫苗)的安全性。方法回顾性分析2003年3月至2019年10月于解放军总医院第五医学中心行肝移植术、术后病情稳定并完成新冠疫苗接种疗程的151例受者的临床资料。统计接种新冠疫苗后受者出现接种部位疼痛, 疲惫感, 头晕头痛, 皮肤瘙痒等的频次。按接种疫苗后有无出现局部及全身反应进行安全性对比分析。同时, 按照疫苗生产企业是北京科兴中维生物技术有限公司(以下简称北京科兴)还是国药集团中国生物北京生物制品研究所有限责任公司(以下简称北京生物), 将完整接种了同一公司2剂疫苗的受者分为北京科兴组和北京生物组;按受者年龄是否大于60岁, 将其分为≥60岁组与<60岁组, 对各组肝移植受者术后接种新型冠状病毒灭活疫苗的安全性进行对比分析。结果本研究151例受者中, 年龄<60岁者98例(<60岁组), ≥60岁者53例(≥60岁组);疫苗接种距离肝移植手术的中位时间为8.44(4.37, 12.39)年;血清中位他克莫司浓度为2.5(1.8, 3.9)ng/L。完整接种了2剂北京科兴生产的新冠疫苗的有83例(北京科兴组)...     

实体器官移植受者新型冠状病毒感染诊疗专家共识(2023年版)

自2019年底以来, 新型冠状病毒(新冠病毒)感染大流行已席卷全球。虽然目前的新冠病毒变异株的致病性和毒力已较原始株有所下降, 大多数患者预后良好, 但实体器官移植(SOT)受者人群为新冠病毒感染脆弱人群, 即使全程接种新冠病毒疫苗, SOT受者感染新冠病毒的住院或死亡风险依然较高。SOT受者新冠病毒感染后其临床表现、诊断和治疗均与普通人群存在很大的特殊性, 需要高度关注。目前尚缺乏针对SOT受者人群可供参考的新冠诊疗领域的指南或共识。因此, 参考《新型冠状病毒诊疗方案(试行第十版)》及国内外文献, 编写团队撰写了《实体器官移植受者新冠病毒感染诊疗专家共识(2023年版)》。本共识基于国内外新冠病毒感染的循证医学证据, 并经过专家多次研讨达成一致意见后撰写成文, 形成21条推荐意见, 为SOT受者感染新冠病毒的诊疗提供参考。     

新型冠状病毒肺炎疫情期器官移植受者随访和感染防治专家建议(试行第一版)

2019年12月底以来,湖北省武汉市及全国各地陆续出现新型冠状病毒肺炎(COVID-19)病例。本建议围绕器官移植受者的特点,简介武汉地区现有器官移植受者感染新型冠状病毒的概况,比较COVID-19与移植后CMV肺炎和耶氏肺孢子虫肺炎的影像学差别,强调COVID-19治疗中的免疫抑制剂调整原则以及对移植器官功能的保护。此外,对特殊时期的移植受者随访也提出建议。     

新型冠状病毒疫苗对心脏机械瓣膜置换术后患者INR值影响的横断面调查

目的 探索心脏机械瓣膜置换术后患者新型冠状病毒（新冠）疫苗的接种率,同时评估其对国际标准化比值（international normalized ratio,INR）的影响。方法 调查2021年5—10月在四川大学华西医院心脏大血管外科门诊随访的心脏机械瓣膜置换术后132例患者新冠疫苗的接种率,其中男51例、女81例,年龄26～72(53.01±9.51)岁。结果 全组患者新冠疫苗接种率为53.8%。61例未接种疫苗患者中,患者担心疫苗对心脏有副作用是影响接种的主要原因。接种后首次复查INR平均值高于接种前最后一次INR值,差值为0.40±0.72,差异有统计学意义（P<0.001）。结论 心脏机械瓣膜置换术后患者新冠疫苗接种率偏低。同时,新冠疫苗可能会提高INR值,接种后建议患者增加复查频率,并相应调整华法林用量。     

SARS-CoV-2 vaccination in solid-organ transplant recipients: What the clinician needs to know

In response to the COVID-19 pandemic, SARS-CoV-2 vaccines have been developed at an unparalleled speed, with 14 SARS-CoV-2 vaccines currently authorized. Solid-organ transplant (SOT) recipients are at risk for developing a higher rate of COVID-19-related complications and therefore they are at priority for immunization against SARS-CoV-2. Preliminary data suggest that although SARS-CoV-2 vaccines are safe in SOT recipients (with similar rate of adverse events than in the general population), the antibody responses are decreased in this population. Risk factors for poor vaccine immunogenicity include older age, shorter time from transplantation, use of mycophenolate and belatacept, and worse allograft function. SOT recipients should continue to be advised to maintain hand hygiene, use of facemasks, and social distancing after SARS-CoV-2 vaccine. Vaccination of household contacts should be also prioritized. Although highly encouraged for research purposes, systematic assessment in clinical practice of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, since correlation between immunological findings and clinical protection from severe COVID-19, and cutoffs for protection are currently unknown in SOT recipients. Alternative immunization schemes, including a booster dose, higher doses, and modulation of immunosuppression during vaccination, need to be assessed in the context of well-designed clinical trials.     

Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus

COVID-19 is associated with increased morbidity and mortality in transplant recipients. There are no efficacy data available regarding these patients with any of the available SARS-CoV-2 vaccines. We analyzed the humoral response following full vaccination with the BNT162b2 (Pfizer-BioNTech) in 136 kidney transplant recipients, and compared it to 25 controls. In order to exclude prior exposure to the virus, only participants with negative serology to SARS-CoV-2 nucleocapsid protein were included. All controls developed a positive response to spike protein, while only 51 of 136 transplant recipients (37.5%) had positive serology (p < .001). Mean IgG anti-spike level was higher in the controls (31.05 [41.8] vs. 200.5 [65.1] AU/mL, study vs. control, respectively, p < .001). Variables associated with null humoral response were older age (odds ratio 1.66 [95% confidence interval 1.17–2.69]), high-dose corticosteroids in the last 12 months (1.3 [1.09–1.86]), maintenance with triple immunosuppression (1.43 [1.06–2.15]), and regimen that includes mycophenolate (1.47 [1.26–2.27]). There was a similar rate of side effects between controls and recipients, and no correlation was found between the presence of symptoms and seroconversion. Our findings suggest that most kidney transplant recipients remain at high risk for COVID-19 despite vaccination. Further studies regarding possible measures to increase recipient's response to vaccination are required.     

Influenza A myocarditis developing in an adult liver transplant recipient despite vaccination: a case report and review of the literature

Solid organ transplant recipients receiving chronic immunosuppressive agents are at increased risk to acquire influenza virus despite vaccination. Myocarditis is a known but rare complication of influenza infection. We present the first adult liver transplant recipient who received prophylactic vaccination but developed influenza A myocarditis. This may occur in solid organ transplant recipients, because they have reduced response to protein vaccines, which may leave them vulnerable to infections. Studies are needed to evaluate if antiviral chemoprophylaxis in solid organ transplant recipients during influenza season would be an effective preventive therapy against influenza in this high-risk population.     

The effect of COVID 19 vaccination on kidney recipients

BackgroundNearly one year from the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, safe and effective vaccines began distribution around the world. This study aimed to assess the rate of COVID-19 disease among vaccinated kidney transplant patients and the types of symptoms found within them.DesignThis cross-sectional study was performed at the transplant ward and Organ Procurement Unit of Sina Hospital, Tehran, Iran. As a sample size, 159 cadavers' kidney recipients received two doses of the Sinopharm SARS-CoV-2 vaccine. The required data were collected using a checklist via conducting a face-to-face interview.ResultsThe mean age of the vaccinated participants was 49.44 ± 13.87 years old. There were 73 (45.91%) vaccinated cases of SARS-CoV-2 infection during the study period, 18 cases (12.6%) occurred among fully vaccinated individuals, and 53 cases (33.3%) were among individuals who had received only one dose of vaccine.45% of the fully vaccinated patients (received 2 doses vaccine) contracted SARS-CoV-2 from their families; 35% were infected through participation in social events (35%).There was a significant difference in disease severity levels between the fully vaccinated group and the one-dose vaccinated (p < 0.023). The severe disease occurred in 2 patients after vaccination, who were subsequently admitted to the hospital.There was a significant difference between the number of kidney transplant days and infection with SARS-CoV-2 before (P = 0.15) and after vaccination (p < 0.015).ConclusionEven after vaccination, kidney recipients are still at the risk of contracting SARS-CoV-2. In addition to these results, the efficacy of vaccination in preventing death caused by SARS-CoV-2 was confirmed.     

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.     

Development of donor specific antibodies after SARS-CoV-2 vaccination in kidney and heart transplant recipients

This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS).     

Kidney transplantation and patients who decline SARS-CoV-2 vaccination: an ethical framework

As SARS-CoV-2 vaccines have started to be rolled out, a key question facing transplant units has been whether listing for transplantation should be contingent on recipients having received a vaccine. We aimed to provide an ethical framework when considering potential transplant candidates who decline vaccination. We convened a working group comprising transplant professionals, lay members and patients and undertook a literature review and consensus process. This group's work was also informed by discussions in two hospital clinical ethics committees. We have reviewed arguments for and against mandating vaccination prior to listing for kidney transplantation and considered some practical difficulties which may be associated with a policy of mandated vaccination. Rather than requiring that all patients must receive the SARS-CoV-2 vaccine prior to transplant listing, we recommend considering vaccination status as one of a number of SARS-CoV-2-related risk factors in relation to transplant listing. Transplant units should engage in individualised risk–benefit discussions with patients, avoid the language of mandated treatments and strongly encourage uptake of the vaccine in all patient groups, using tailor-made educational initiatives.     

Influenza vaccination in the organ transplant recipient: review and summary recommendations

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high-dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.     

Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients

Knowledge on the immunogenicity of vector-based and mRNA-vaccines in solid organ transplant recipients is limited. Therefore, SARS-CoV-2–specific T cells and antibodies were analyzed in 40 transplant recipients and 70 controls after homologous or heterologous vaccine-regimens. Plasmablasts and SARS-CoV-2–specific CD4 and CD8 T cells were quantified using flow cytometry. Specific antibodies were analyzed by ELISA and neutralization assay. The two vaccine types differed after the first vaccination, as IgG and neutralizing activity were more pronounced after mRNA priming (p = .0001 each), whereas CD4 and CD8 T cell levels were higher after vector priming (p = .009; p = .0001). All regimens were well tolerated, and SARS-CoV-2–specific antibodies and/or T cells after second vaccination were induced in 100% of controls and 70.6% of transplant recipients. Although antibody and T cell levels were lower in patients, heterologous vaccination led to the most pronounced induction of antibodies and CD4 T cells. Plasmablast numbers were significantly higher in controls and correlated with SARS-CoV-2–specific IgG- and T cell levels. While antibodies were only detected in 35.3% of patients, cellular immunity was more frequently found (64.7%) indicating that assessment of antibodies is insufficient to identify COVID-19-vaccine responders. In conclusion, heterologous vaccination seems promising in transplant recipients, and combined analysis of humoral and cellular immunity improves the identification of responders among immunocompromised individuals.     

What solid organ transplant healthcare providers should know about renin-angiotensin-aldosterone system inhibitors and COVID-19

The data on the outcomes of solid organ transplant recipients who have contracted coronavirus disease 2019 (COVID-19) are still emerging. Kidney transplant recipients are commonly prescribed renin-angiotensin-aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS-CoV-2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID-19 pandemic. At present, there is no clear evidence to support the discontinuation of RAAS inhibitors in solid organ transplant recipients during the COVID-19 pandemic.