OBJECTIVES:

The outbreak of coronavirus disease 2019, known as COVID-19, has rapidly evolved to a global pandemic. This pandemic represents an unprecedented public health issue not only for the general population but also for patients on the transplant wait list. Multiple organizations around the world have published recommendations for the proper conduct of transplant procedures, including donor and recipient screening and perioperative management. We investigated the efficacy of these new recommendations and the effects of SARS-CoV-2 infection on the deceased donation rate, donor organ management, and the time from family consent to procurement.

MATERIALS AND METHODS:

The characteristics of potential donors diagnosed with brain death between July 15, 2019, and November 18, 2020, were evaluated retrospectively.Demographic and clinical features,the time elapsed from the clinical diagnosis until confirmation, and rates of acceptance were recorded. Potential donors diagnosed with brain death before the pandemic and during the pandemic were compared according to these variables.

RESULTS:

Within the study period, 40 patients were diagnosed with brain death: 13 before the pandemic and 27 during the pandemic. The organs from 2 donors were procured before the pandemic. Organs from 3 of 8 donors were procured during the pandemic (the organs from 5 of these 8 patients were not donated). The organ donation time was 8.5 ± 2.12 hours (minimum-maximum, 7-10 hours) in the period before the pandemic and 54 ± 11.53 hours (minimummaximum, 45-67 hours) during the pandemic.

CONCLUSIONS:

The number of donors decreased significantly in our hospital during the pandemic and was similarto the overallrate inTurkey.The duration of the donation process has been prolonged, and strategies to improve rates of organ donation, including infection control, have become a focus of concern.

INTRODUCTION:

The COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation (SOT).

OBJECTIVES:

We aimed to assess a cohort of transplant recipients who developed COVID‑19, with a focus on immunosuppressive regimen, blood tacrolimus levels, clinical course, and patient and graft outcomes.

PATIENTS AND METHODS:

During the first 12 months of the pandemic, we identified ambulatory SOT recipients, including kidney, liver, and heart transplant recipients, diagnosed with SARS‑CoV‑2 infection. Baseline and follow‑up data on graft function, immunosuppression, and patient and graft outcomes were assessed.

RESULTS:

Of the 2091 ambulatory patients, we identified 201 transplant recipients (9.6%) with SARS‑CoV‑2 infection (kidney transplant, n = 112; heart transplant, n = 56; liver transplant, n = 33). Patients after recent kidney (during 2015-2020) or heart (during 2020) transplant were significantly more often diagnosed with COVID ‑19 than patients with a longer time since transplant. Additionally, blood trough tacrolimus levels measured during or shortly after COVID‑19 in 23 kidney graft recipients were significantly increased by a median of 76.1% (interquartile range, 47.4%-109.4%) relative to predose trough levels. However, liver function parameters were not elevated, necessitating a tacrolimus dose reduction in 73.9% of the patients.

CONCLUSIONS:

In our study, kidney transplant recipients showed significant disturbances of tacrolimus metabolism, which may account for kidney function worsening during COVID‑19. Moreover, infection was more common in patients with recent kidney or heart transplant, which suggests that the level of immunosuppression may affect morbidity related to SARS‑CoV‑2 infection.

BACKGROUND:

The COVID-19 pandemic has uniquely affected the United States. We hypothesize that transplantation would be uniquely affected.

METHODS:

In this population-based cohort study, adult transplantation data were examined as time series data. Autoregressive-integrated-moving-average models of transplantation rates were developed using data from 1990 to 2019 to forecast the 2020 expected rates in a theoretical scenario if the pandemic did not occur to generate observed-to-expected (O/E) ratios.

RESULTS:

32,594 transplants were expected in 2020, and only 30,566 occurred (O/E 0.94, CI 0.88-0.99). 58,152 waitlist registrations were expected and 50,241 occurred (O/E 0.86, CI 0.80-0.94). O/E ratios of transplants were kidney 0.92 (0.86-0.98), liver 0.96 (0.89-1.04), heart 1.05 (0.91-1.23), and lung 0.92 (0.82-1.04). O/E ratios of registrations were kidney 0.84 (0.77-0.93), liver 0.95 (0.86-1.06), heart 0.99 (0.85-1.18), and lung 0.80 (0.70-0.94).

CONCLUSIONS:

The COVID-19 pandemic was associated with a significant deficit in transplantation. The impact was strongest in kidney transplantation and waitlist registration.

OBJECTIVES:

The recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.

METHODS:

This was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.

RESULTS:

Of the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients.

DISCUSSION:

A third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.

Response to two doses of a nucleoside-modified messenger ribonucleic acid (mRNA) vaccine was evaluated in a large solid-organ transplant program. mRNA COVID-19 vaccine was administered to transplant candidates and recipients who met study inclusion criteria. Qualitative anti-SARS-CoV-2 Spike Total Immunoglobulin (Ig) and IgG-specific assays, and a semi-quantitative test for anti-SARS-CoV-2 Spike protein IgG were measured in 241 (17.2%) transplant candidates and 1163 (82.8%) transplant recipients; 55.2% of whom were non-Hispanic White and 44.8% identified as another race. Transplant recipients were a median (IQR) of 3.2 (1.1, 6.8) years from transplantation. Response differed by transplant status: 96.0% versus 43.2% by the anti-SARS-CoV-2 Total Ig (candidates vs. recipients, respectively), 93.5% versus 11.6% by the anti-SARS-CoV-2 IgG assay, and 91.9% versus 30.1% by anti-spike titers after two doses of vaccine. Multivariable analysis revealed candidates had higher likelihood of response versus recipients (odds ratio [OR], 14.6; 95 %CI 2.19, 98.11; P = .02). A slightly lower response was demonstrated in older patients (OR .96; 95 %CI .94, .99; P = .002), patients taking antimetabolites (OR, .21; 95% CI .08, .51; P = .001). Vaccination prior to transplantation should be encouraged.

BACKGROUND:

More patients are waitlisted for solid organs than transplants are performed each year. The COVID-19 pandemic immediately increased waitlist mortality and decreased transplants and listings.

METHODS:

To calculate the number of candidate listings after the pandemic began and short-term changes that may affect waiting time, we conducted a Scientific Registry of Transplant Recipients surveillance study from January 1, 2012 to February 28, 2021.

RESULTS:

The number of candidates on the liver waitlist continued a steady decline that began before the pandemic. Numbers of candidates on the kidney, heart, and lung waitlists decreased dramatically. More than 3000 fewer candidates were awaiting a kidney transplant on March 7, 2021, than on March 8, 2020. Listings and removals decreased for each solid organ beginning in March 2020. The number of heart and lung listings returned to equal or above that of removals. Listings for kidney transplant, which is often less urgent than heart and lung transplant, remain below numbers of removals. Removals due to transplant decreased for all organs, while removals due to death increased for only kidneys.

CONCLUSIONS:

We found no evidence of the predicted surge in listings for solid organ transplant with a plateau or control of the pandemic.