Organ transplantation using COVID-19-positive deceased donors.

The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed. We hypothesize that COVID-19 infection of deceased solid organ transplant donors does not affect recipient survival. All deceased solid organ transplant donors with COVID-19 testing results from March 15, 2020 to September 30, 2021 were identified in the OPTN database. Donors were matched to recipients and stratified by the COVID-19 test result. Outcomes were assessed between groups. COVID-19 test results were available for 17 694 donors; 150 were positive. A total of 269 organs were transplanted from these donors, including 187 kidneys, 57 livers, 18 hearts, 5 kidney-pancreases, and 2 lungs. The median time from COVID-19 testing to organ recovery was 4 days for positive and 3 days for negative donors. Of these, there were 8 graft failures (3.0%) and 5 deaths (1.9%). Survival of patients receiving grafts from COVID-19-positive donors is equivalent to those receiving grafts from COVID-19-negative donors (30-day patient survival = 99.2% COVID-19 positive; 98.6% COVID-19 negative). Solid organ transplantation using deceased donors with positive COVID-19 results does not negatively affect early patient survival, though little information regarding donor COVID-19 organ involvement is known. While transplantation is feasible, more information regarding COVID-19-positive donor selection is needed.

Incidence and severity of SARS-CoV-2 infections in liver and kidney transplant recipients in the post-vaccination era: Real-life data from Denmark.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre-vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID-19 in kidney and liver transplant recipients in Denmark in the post-vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first-positive SARS-CoV-2 PCR test. The cumulative incidence of first-positive SARS-CoV-2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8-12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4-13.8] vs. 7.4% [95% CI: 5.1-9.8], p = .009). After the first-positive SARS-CoV-2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9-39.1), and 30-day all-cause mortality was 3.7% (95% CI: 0.5-6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1-34.6] vs. 48.5% [95% CI: 31.4-65.5], p = .011), as was mortality (1.8% [95% CI: 0.0-4.3] vs. 9.1% [95% CI: 0.0-18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS-CoV-2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

COVID-19 and transplantation-Data censoring.

During the early wave of the COVID-19 pandemic, the Scientific Registry of Transplant Recipients (SRTR) designated a "black out" period between March 12, 2020, and June 12, 2020, for transplant outcomes reporting. We discuss the implications and potential bias it has introduced as it may selectively favor the outcomes for certain regions and harm other regions due to varied effects of different waves of COVID-19 infections across the United States.

Quantifying excess deaths among solid organ transplant recipients in the COVID-19 era.

Estimating the total coronavirus disease 2019 (COVID-19) mortality burden of solid organ transplant recipients (SOTRs), both directly through COVID-19 infection and indirectly through other impacts on the healthcare system and society, is critical for understanding the disease's impact on the SOTR population. Using SRTR data, we modeled expected mortality risk per month pre-COVID (January 2015-February 2020) for kidney/liver/heart/lung SOTRs, and compared monthly COVID-era deaths (March 2020-March 2021) to expected rates, overall and among subgroups. Deaths above expected rates were designated "excess deaths." Between March 2020 and March 2021, there were 3739/827/265/252 excess deaths among kidney/liver/heart/lung SOTRs, respectively, representing a 41.2%/27.4%/18.5%/15.0% increase above expected deaths. 93.0% of excess deaths occurred in patients age≥50. The observed:expected ratio was highest among Hispanic SOTRs (1.82) and lowest among White SOTRs (1.20); 56.0% of excess deaths occurred among Black or Hispanic SOTRs. 64.7% of excess deaths occurred among patients who had survived ≥5 years post-transplant. Excess deaths peaked in January 2021; geographic distribution of excess deaths broadly mirrored COVID-19 incidence. COVID-19 likely caused over 5000 excess deaths among SOTRs in the US in a 13-month period, representing 1 in 75 SOTRs and a substantial proportion of all deaths among SOTRs during this time. SOTRs will remain at elevated mortality risk until the COVID-19 pandemic can be controlled.

The course of the novel coronavirus infection COVID-19 in recipients of solid organs, depending on the type of maintenance immunosuppression according to the local transplant register

Background. The novel coronavirus infection COVID-19 has had a significant impact on organ transplantation in the world, both by reducing the availability of deceased donor organs due to the overload of intensive care units with patients with viral pneumonia, and due to the severe course of infection in patients after transplantation secondary to maintenance immunosuppression. The composition of maintenance immunosuppression in a patient after transplantation may affect the course of coronavirus infection. Study purpose. Based on the local transplant Register analysis, determine the effect of the composition of maintenance immunosuppression on the outcome of COVID-19 in organ transplant recipients. Material and methods. In March 2020, due to the COVID-19 pandemic, additional blocks characterizing the COVID-19 in a patient were introduced into the modules of the Register. The analytical section of the Register allows to compare the results of transplantation in patients' groups arbitrarily formed by the researcher. Daily updating of data allows to analyze actual information. An analysis of COVID-19 outcomes in recipients of donor organs is carried out depending on the composition of maintenance immunosuppression. Results. Between February 2020 and April 2021, the Register identified 72 recipients with COVID-19, of them 41 were on steroid-free immunosuppression. Recovered 93% of steroid-free patients and 48% of steroid based patients, mortality rate was 5 vs 42%, graft loss was 2 vs 10%. Conclusion. The Transplant Register, which exists in the legal field of Russian legislation, taking into account information about transplants performed in specific medical centers to specific patients, their effectiveness, including the practice of their rehabilitation and medical support, allows timely identification of successful practices, including in new conditions arising in connection with the COVID-19 pandemic. Maintenance immunosuppression without steroids significantly increase the chances of a favorable outcome of COVID-19 in organ transplant recipients. © 2021 GEOTAR Media. All rights reserved.

Use of anti-spike monoclonal antibodies in kidney transplant recipients with COVID-19: Efficacy, ethnic and racial disparities.

Organ transplant recipients may not mount an adequate immune response to COVID-19 infection and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAbs), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. We identified KTR with COVID-19 between March 1, 2020 and April 30, 2021. Patients were excluded if they had multi-organ transplant or hospital-acquired COVID-19. We studied 95 KTR; 20 received mAb. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15% vs. 76%, p < 0.001). This association remained significant after adjustment for potential confounders, and analysis of mAb administration as a time-dependent variable, with day of symptom onset as day 1 (adjusted HR 0.216, p = 0.04). Black or Hispanic patients were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER. In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, have been exacerbated by the COVID-19 pandemic. Antiviral mAbs are a promising therapeutic modality, especially for immunocompromised patients.

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.

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

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.

Incidence and outcome of SARS-CoV-2 infection on solid organ transplantation recipients: A nationwide population-based study.

Since February 21 2020, when the Italian National Institute of Health (Istituto Superiore di Sanità-ISS) reported the first autochthonous case of infection, a dedicated surveillance system for SARS-CoV-2-positive (COVID+) cases has been created in Italy. These data were cross-referenced with those inside the Information Transplant System in order to assess the cumulative incidence (CI) and the outcome of SARS-COV-2 infection in solid organ transplant recipients (SOTRs) who are assumed to be most at risk. We compared our results with those of COVID+ nontransplanted patients (Non-SOTRs) with follow-up through September 30, 2020. The CI of SARS-CoV-2 infection in SOTRs was 1.02%, higher than in COVID+ Non-SOTRs (0.4%, p < .05) with a greater risk in the Lombardy region (2.89%). The CI by type of organ transplant was higher for heart (CI 1.57%, incidence rate ratio [IRR] 1.36) and lower for liver (CI 0.63%, IRR 0.54). The 60-day CI of mortality was 30.6%, twice as much that of COVID+ Non-SOTRs (15.4%) with a 60-day gender and age adjusted odds ratio (adjusted-OR) of 3.83 for COVID+ SOTRs (95% confidence interval [3.03-4.85]). The lowest 60-day adjusted-OR was observed in liver SOTRs (OR 0.46, 95% confidence interval [0.25-0.86]). More detailed studies on disease management and evolution will be necessary in these patients at greater risk of COVID-19.

Impact of Timely Public Health Measures on Kidney Transplantation in Austria during the SARS-CoV-2 Outbreak-A Nationwide Analysis.

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death; 10%) in renal transplant patients was less than in other countries but higher than in Austria's general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future.

COVID-19 outcomes in patients waitlisted for kidney transplantation and kidney transplant recipients.

The COVID-19 pandemic has brought unprecedented challenges to the transplant community. The reduction in transplantation volume during this time is partly due to concerns over potentially increased susceptibility and worsened outcomes of COVID-19 in immunosuppressed recipients. The consequences of COVID-19 on patients waitlisted for kidney transplantation, however, have not previously been characterized. We studied 56 waitlisted patients and 80 kidney transplant recipients diagnosed with COVID-19 between March 13 and May 20, 2020. Despite similar demographics and burden of comorbidities between waitlisted and transplant patients, waitlisted patients were more likely to require hospitalization (82% vs. 65%, P = .03) and were at a higher risk of mortality (34% vs. 16%, P = .02). Intubation was required in one third of hospitalized patients in each group, and portended a very poor prognosis. The vast majority of patients who died were male (84% waitlist, 100% transplant). Multivariate analysis demonstrated waitlist status, age, and male sex were independently associated with mortality. COVID-19 has had a dramatic impact on waitlisted patients, decreasing their opportunities for transplantation and posing significant mortality risk. Understanding the impact of COVID-19 on waitlist patients in comparison to transplant recipients may aid centers in weighing the risks and benefits of transplantation in the setting of ongoing COVID-19.

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.

Clinical characteristics and risk factors for severe COVID-19 in hospitalized kidney transplant recipients: A multicentric cohort study.

Kidney transplant recipients might be at higher risk for severe coronavirus disease 2019 (COVID-19). However, risk factors for relevant outcomes remain uncertain in this population. This is a multicentric kidney transplant cohort including 104 hospitalized patients between March 4 and April 17, 2020. Risk factors for death and acute respiratory distress syndrome (ARDS) were investigated, and clinical and laboratory data were analyzed. The mean age was 60 years. Forty-seven patients (54.8%) developed ARDS. Obesity was associated to ARDS development (OR 2.63; P = .04). Significant age differences were not found among patients developing and not developing ARDS (61.3 vs 57.8 years, P = .16). Seventy-six (73%) patients were discharged, and 28 (27%) died. Death was more common among the elderly (55 and 70.8 years, P < .001) and those with preexisting pulmonary disease (OR 2.89, P = .009). At admission, higher baseline lactate dehydrogenase (257 vs 358 IU/mL, P = .001) or ARDS conferred higher risk of death (HR 2.09, P = .044). In our cohort, ARDS was equally present among young and old kidney recipients. However, the elderly might be at higher risk of death, along with those showing higher baseline LDH at admission.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Heart transplantation in the era of the SARS-CoV-2 pandemic: Is it safe and feasible?

As the SARS-CoV-2-pandemic continues to unfold, the number of heart transplants completed in the United States has been declining steadily. The current case series examines the immediate short-term outcomes of seven heart transplant recipients transplanted during the SARS-CoV-2 pandemic. We hope to illustrate that with proper preparation, planning, and testing, heart transplantation can be continued during a pandemic. We assessed 7 patients transplanted from March 4, 2020, to April 15, 2020. The following endpoints were noted: in-hospital survival, in-hospital freedom from rejection, in-hospital nonfatal major cardiac adverse events (NF-MACE), severe primary graft dysfunction, hospital length of stay, and ICU length of stay. There were no expirations throughout the hospital admission. In addition, there were no patients with NF-MACE or treated rejection, and 1 patient developed severe primary graft dysfunction. Average length of stay was 17.2 days with a standard deviation of 5.9 days. ICU length of stay was 7.7 days with a standard deviation of 2.3 days. Despite the decreasing trend in completed heart transplants due to SARS-CoV-2, heart transplantation appears to be feasible in the immediate short term. Further follow-up is needed, however, to assess the impact of SARS-CoV-2 on post-heart transplant outcomes months after transplantation.

Early national and center-level changes to kidney transplantation in the United States during the COVID-19 epidemic.

In March 2020, coronavirus disease 2019 (COVID-19) spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center levels, accounting statistically for waitlist composition. Using Scientific Registry of Transplant Recipients data, we compared data on observed waitlist registrations, waitlist mortality, and living-donor and deceased-donor kidney transplants (LDKT/DDKT) March 15-April 30, 2020 to expected events calculated from preepidemic data January 2016-February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all P < .001). Only 12 centers performed LDKT March 15-31; by April 30, 40 centers had resumed LDKT. The decline in new listings and DDKT was greater among states with higher per capita confirmed COVID-19 cases. The number of waitlist deaths was 2.2-fold higher than expected in the 5 states with highest COVID-19 burden (P < .001). DCD DDKT and regional/national imports declined nationwide but most steeply in states with the highest COVID-19 burden. The COVID-19 epidemic has resulted in substantial changes to KT; we must adapt and learn rapidly to continue to provide safe access to transplantation and limit the growing indirect toll of an already deadly disease.