Summary
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.
Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population‐based studies have quantified and ...compared cancer risks according to graft type and with long‐term follow‐up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow‐up of 93,432 person‐years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIRcancer excl SCC 2.4 (95% CI, 2.2–2.5); SIRSCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIRcancer excl SCC 3.3 (95% CI, 2.8–4.0); SIRSCC 198 (95% CI, 174–224), followed by kidney SIRcancer excl SCC 2.3 (95% CI, 2.1–2.4); SIRSCC 121 (95% CI, 116–127) and liver recipients SIRcancer excl SCC 2.3 (95% CI, 1.9–2.8); SIRSCC 32 (95% CI, 24–42). During follow‐up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post‐transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.
What's new?
After an organ transplant, the immune system must be permanently suppressed, to allow the foreign organ to survive in the body. With the immune system stifled, viruses that cause cancer have a much easier time of it, and transplant recipients are known to have increased cancer risk. The present study examined more than 10,000 organ transplant recipients over a 20‐year period to determine their risk of various cancers, including skin cancer, which had not been included in previous studies. They found that the risk of squamous cell carcinoma shot up 100‐fold overall, while the risk of other cancers doubled. These detailed estimates of risk over time will greatly assist doctors working with these transplant patients.
Regulatory T Cells and Human Disease Sakaguchi, Shimon; Mikami, Norihisa; Wing, James B ...
Annual review of immunology,
04/2020, Letnik:
38, Številka:
1
Journal Article
Recenzirano
Naturally occurring CD4
+
regulatory T cells (Tregs), which specifically express the transcription factor FoxP3 in the nucleus and CD25 and CTLA-4 on the cell surface, are a functionally distinct T ...cell subpopulation actively engaged in the maintenance of immunological self-tolerance and homeostasis. Recent studies have facilitated our understanding of the cellular and molecular basis of their generation, function, phenotypic and functional stability, and adaptability. It is under investigation in humans how functional or numerical Treg anomalies, whether genetically determined or environmentally induced, contribute to immunological diseases such as autoimmune diseases. Also being addressed is how Tregs can be targeted to control physiological and pathological immune responses, for example, by depleting them to enhance tumor immunity or by expanding them to treat immunological diseases. This review discusses our current understanding of Treg immunobiology in normal and disease states, with a perspective on the realization of Treg-targeting therapies in the clinic.
Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease ...among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described.
Methods
We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients.
Results
Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range IQR 46–57), median time post-transplant was 5 years (IQR 2–10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 78%), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 adjusted odds ratio aOR 3.0, 95% confidence interval CI 1.7–5.5, P < .001, congestive heart failure aOR 3.2, 95% CI 1.4–7.0, P = .004, chronic lung disease aOR 2.5, 95% CI 1.2–5.2, P = .018, obesity aOR 1.9, 95% CI 1.0–3.4, P = .039) and presenting findings (lymphopenia aOR 1.9, 95% CI 1.1–3.5, P = .033, abnormal chest imaging aOR 2.9, 95% CI 1.1–7.5, P = .027) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality.
Conclusions
Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.
In this analysis of 482 solid organ transplant recipients with coronavirus disease 2019 (COVID-19), the authors report 28-day mortality of 20.5% among inpatients, strongly associated with age and comorbidities, and conclude that this is comparable to rates observed in the general population.
Kidney‐alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi‐organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving ...a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas–kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the “next‐sequential KAT candidate” who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next‐sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next‐sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match‐run, mortality risk was significantly higher for next‐sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.
This study assesses characteristics and subsequent outcomes of kidney‐alone transplant candidates who were next in sequence on a given kidney match run, but did not receive a potential organ offer due to its allocation for multi‐organ transplantation. See an editorial from Schold and Mohan on page 2004.
Following the birth of the first child from a transplanted uterus in Gothenburg, Sweden, in 2014, other centers worldwide have produced scientific reports of successful uterus transplantation, as ...well as more recent media reports of successful births. The American Society for Reproductive Medicine recognizes uterus transplantation as the first successful medical treatment of absolute uterus factor infertility, while cautioning health professionals, patient advocacy groups, and the public about its highly experimental nature.
The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after solid organ transplant (SOT) ...remain unknown. We report our preliminary experience with 18 SOT (kidney 44.4%, liver 33.3%, and heart 22.2%) recipients diagnosed with COVID‐19 by March 23, 2020 at a tertiary‐care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon‐β (16.7%). As of April 4, the case‐fatality rate was 27.8% (5/18). After a median follow‐up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C‐reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS‐CoV‐2 infection has a severe course in SOT recipients.
In the present experience with 18 transplant recipients diagnosed with COVID‐19 by March 23, 2020 at their institution in Madrid, the authors found a case fatality rate of 27.8%, with 30.8% of survivors developing progressive respiratory failure or acute respiratory distress syndrome.
Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with ...SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.
In this multicenter study of 90 solid organ transplant recipients diagnosed with COVID‐19 during the first three weeks of the outbreak in New York City, the authors report on the clinical presentation, laboratory abnormalities, risk factors, disease severity, and outcomes.
Alcohol and cannabis use as a contraindication to organ transplantation is a controversial issue. Until recently, patients in Canada with alcohol-associated liver disease were required to demonstrate ...abstinence for 6 mo to receive a liver transplant. There is no equivalent rule that is applied consistently for cannabis use. There is some evidence that alcohol and cannabis use disorder pretransplant could be associated with worse outcomes posttransplantation. However, early liver transplantation for patients with alcohol-associated liver disease in France and in the United States has led to challenges of the 6-mo abstinence rule in Canada in the media. It has also resulted in several legal challenges arguing that the rule violates human rights laws regarding discrimination in the provision of medical services and that the rule is also unconstitutional (this challenge is still before the court). Recent legalization of cannabis use for adults in Canada has led to questions about the appropriateness of limiting transplant access based on cannabis use. The ethics committee of the Canadian Society of Transplantation was asked to provide an ethical analysis of cannabis and alcohol abstinence policies. Our conclusions were as follows: neither cannabis use nor the 6-mo abstinence rule for alcohol use should be an absolute contraindication to transplantation, and transplant could be offered to selected patients, further research should be conducted to ensure evidence-based policies; and the transplant community has a duty not to perpetuate stigma associated with alcohol and cannabis use disorders.
In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) ...recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% CI 1.08-1.197) higher levels of C-reactive protein (OR 3.068; 95% CI 1.22-7.71) and levels of serum creatinine on admission (OR 3.048 95% CI 1.22-7.57) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.
PDF
