Impact of COVID-19 in solid organ transplant recipients

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients.     

COVID-19 in solid organ transplant recipients: a single-center experience

Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT. Demographic, clinical, and treatment data were extracted from the electronic patient files. A total of 23 SOT transplant recipients suffering from COVID-19 were identified (n = 3 heart; n = 15 kidney; n = 1 kidney-after-heart; n = 3 lung, and n = 1 liver transplant recipient). The presenting symptoms were similar to nonimmunocompromised patients. Eighty-three percent (19/23) of the patients required hospitalization, but only two of these were transferred to the intensive care unit. Five patients died from COVID-19; all had high Clinical Frailty Scores. In four of these patients, mechanical ventilation was deemed futile. In 57% of patients, the immunosuppressive therapy was not changed and only three patients were treated with chloroquine. Most patients recovered without experimental antiviral therapy. Modification of the immunosuppressive regimen alone could be a therapeutic option for SOT recipients suffering from moderate to severe COVID-19. Pre-existent frailty is associated with death from COVID-19.     

Attenuated early inflammatory response in solid organ recipients with COVID-19

Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. The specific features of coronavirus disease 2019 (COVID-19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig-Maximilians-University Munich because of COVID-19 and tested positive for SARS-CoV-2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18, and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after 10 and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non-transplanted patients at the ICU (n = 19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL-6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS-CoV-2, their clinical course seems to be similar to immunocompetent patients.     

Mortality among solid organ waitlist candidates during COVID-19 in the United States

We examined the effects of COVID-19 on solid organ waiting list mortality in the United States and compared effects across patient demographics (e.g., race, age, and sex) and donation service areas. Three separate piecewise exponential survival models estimated for each solid organ the overall, demographic-specific, and donation service area-specific differences in the hazard of waitlist mortality before and after the national emergency declaration on March 13, 2020. Kidney waiting list mortality was higher after than before the national emergency (adjusted hazard ratio [aHR], 1.37; 95% CI, 1.23–1.52). The hazard of waitlist mortality was not significantly different before and after COVID-19 for liver (aHR, 0.94), pancreas (aHR, 1.01), lung (aHR, 1.00), and heart (aHR, 0.94). Kidney candidates had notable variability in differences across donation service areas (aHRs, New York City, 2.52; New Jersey, 1.84; and Michigan, 1.56). The only demographic group with increased waiting list mortality were Blacks versus Whites (aHR, 1.41; 95% CI, 1.07–1.86) for kidney candidates. The first 10 weeks after the declaration of a national emergency had a heterogeneous effect on waitlist mortality rate, varying by geography and ethnicity. This heterogeneity will complicate comparisons of transplant program performance during COVID-19.     

COVID-19 in solid organ transplant recipients: A national cohort study from Sweden

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1–2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6–7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.     

新型冠状病毒肺炎疫情期间肝移植病房管理单中心经验

自2019年12月发生的新型冠状病毒肺炎(COVID-19)影响范围广、感染人数多,在对社会生活造成严重影响的同时,也给医院器官移植病房的管理带来了巨大挑战。肝移植受者术后免疫力低下,新型冠状病毒(2019-nCoV)易感性可能较普通人群更高。因此,肝移植病房的管理具有其特殊性。COVID-19疫情期间,青岛大学附属医院肝脏移植科医护人员通过学习国家卫生健康委员会发布的COVID-19防控和诊疗方案以及相关指南,加强医护人员自身防护,制订适应疫情形势的住院患者管理流程,完善患者及其家属COVID-19相关知识宣教,建立并优化肝移植病房管理方案。期望通过特殊时期肝移植病房的有效管理,在予肝移植受者科学治疗的同时,有效避免2019-nCoV感染。     

Pediatric solid organ transplantation

Solid organ transplantation offers hope for long-term survival and more normal lifestyles for children. Many of the procedures used are scaled-down versions of those used in adults and are associated with distinct challenges in children. Recent studies have provided insights into how transplantation can best serve these patients.     

COVID-19 and kidney transplantation

The COVID-19 pandemic affects the transplant recipients since March 2020. Transplant centers quickly organized themselves to optimize the management of the immunocompromised patients and to progress in the knowledge of this new disease. To this end, a French Registry was created, which includes all solid organ transplant patients who have developed a SARS Cov2 infection. Numerous studies have been carried out using these data to describe this new disease in transplant patients, to characterize its clinical and biological risk factors and to define its prognosis. The 60 days-mortality of transplant patients hospitalized for COVID-19 was evaluated at 23% and renal failure plays a major role in the poor prognosis in addition to the classical risk factors described in the general population. The advent of vaccination has been a great relief but transplanted patients have shown a poor vaccine response keeping them at risk of severe disease even after an adapted vaccination scheme. Specific strategies was proposed in this particularly fragile population like increasing vaccine doses or using anti SARS Cov-2 monoclonal antibodies.     

Inpatient COVID-19 outcomes in solid organ transplant recipients compared to non-solid organ transplant patients: A retrospective cohort

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID-19, as suggested by recent case series. We compared 45 SOT vs. 2427 non-SOT patients who were admitted with COVID-19 to our health-care system (March 1, 2020 - August 21, 2020), evaluating hospital length-of-stay and inpatient mortality using competing-risks regression. We compared trajectories of WHO COVID-19 severity scale using mixed-effects ordinal logistic regression, adjusting for severity score at admission. SOT and non-SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p < .001), hypertension (69% vs. 44%, p = .001), HIV (7% vs. 1.4%, p = .024), and peripheral vascular disorders (19% vs. 8%, p = .018). There were no statistically significant differences between SOT and non-SOT in maximum illness severity score (p = .13), length-of-stay (sHR: _0.91.1_1.4, p = .5), or mortality (sHR: _0.10.4_1.6, p = .19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non-SOT (median [IQR] 4 [3–4]) (p = .042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = _0.760.81_0.86, p < .001) compared with non-SOT patients. These findings have implications for transplant decision-making during the COVID-19 pandemic, and insights about the impact of SARS-CoV-2 on immunosuppressed patients.

     

美国器官捐献和移植立法主要事件

1968年哈佛大学提出“脑死亡定义”1968年《人体器官捐献法》对以移植为目的的器官和组织捐献进行了法律规范 1971年修订《人体器官捐献法》，赋予器官捐献卡片法律效力     

Gynecologic cancers and solid organ transplantation

Solid organ transplant (SOT) recipients have an approximately 2‐fold greater risk of developing and dying from a malignancy compared to the general population. Among the gynecologic cancers, including uterine, cervical, vaginal, vulvar, and ovarian, the HPV‐related cancers are known to increase among women posttransplant compared to women in the general population, but less is known about the risk of uterine and ovarian cancers. This review provides an overview of the epidemiology of gynecologic cancers after solid organ transplantation, as well as the pathophysiology, management, and specific risk factors associated with these cancers. Closer surveillance for cervical cancers is warranted and larger studies are needed to assess whether and how uterine and ovarian cancers are associated with excess incidence and mortality. Such studies may lead to improvements in screening, prevention, and treatment before and after transplantation.     

Chagas' disease and solid organ transplantation

This review summarizes relevant published data on transplant recipients with Chagas' disease and of naïve recipients transplanted with organs from infected donors. Unpublished experience from some of the largest transplant centers in Argentina is also included. The review outlines the guidelines for pretransplant evaluation and for posttransplant management formulated by the Chagas Disease Argentine Collaborative Transplant Consortium.     

Immunologic response and seroconversion following third-dose COVID-19 vaccination in solid organ transplant recipients: A meta-analysis

IntroductionThe immunogenicity and efficacy of COVID-19 vaccination varied by demographic, including solid organ transplant recipients on immunosuppressive therapy.AimThis purpose of this study is to assess seropositivity and seroconversion in solid-organ transplant recipients before and after third-dose COVID-19 vaccination.MethodsThis study is a systematic review and meta-analysis performed using PRISMA guidelines. To analyze clinical and cohort studies reporting immunologic response and seroconversion third-dose vaccination, a systematic search was performed using electronic databases (PubMed, Scopus, Cochrane, Directory of Open Access Journal (DOAJ), and Clinicaltrials.gov).ResultThere were 18 full-text papers that could be analyzed qualitatively and quantitatively. After the third vaccination, the pooled rate seropositivity was 67.00% (95% CI 59.511; 74.047, I2 = 93.82%), and the pooled rate seroconversion was 52.51% (95% CI 44.03; 60.91, I2 = 92.15%). The pooled rate of seroconversion after the mRNA-based booster was 52.380% (95% CI 40.988; 63.649, I2 = 94.35%), and after the viral-vector-based booster was 42.478% (95% CI 35.222; 49.900, I2 = 0.00%).ConclusionBased on the analysis of immunologic responses and seroconversion findings, the third-dose vaccination of solid organ transplant recipients is an effective method in establishing better immunity against COVID-19.