Differences in Humoral and Cellular Vaccine Responses to SARS-CoV-2 in Kidney and Liver Transplant Recipients.

The antibody and T cell responses after SARS-CoV-2 vaccination have not been formally compared between kidney and liver transplant recipients. Using a multiplex assay, we measured IgG levels against 4 epitopes of SARS-CoV-2 spike protein and nucleocapsid (NC) antigen, SARS-CoV-2 variants, and common coronaviruses in serial blood samples from 52 kidney and 50 liver transplant recipients undergoing mRNA SARS-CoV-2 vaccination. We quantified IFN-γ/IL-2 T cells reactive against SARS-CoV-2 spike protein by FluoroSpot. We used multivariable generalized linear models to adjust for the differences in immunosuppression between groups. In liver transplant recipients, IgG levels against every SARS-CoV-2 spike epitope increased significantly more than in kidney transplant recipients (MFI: 19,617 vs 6,056; P<0.001), a difference that remained significant after adjustments. Vaccine did not affect IgG levels against NC nor common coronaviruses. Elicited antibodies recognized all variants tested but at significantly lower strength than the original Wuhan strain. Anti-spike IFN-γ-producing T cells increased significantly more in liver than in kidney transplant recipients (IFN-γ-producing T cells 28 vs 11 spots/5x105 cells), but this difference lost statistical significance after adjustments. SARS-CoV-2 vaccine elicits a stronger antibody response in liver than in kidney transplant recipients, a phenomenon that is not entirely explained by the different immunosuppression.

Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

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.

COVID-19 Aftershocks on Alcohol-Associated Liver Disease: An Early Cross-Sectional Report From the U.S. Epicenter.

Experts have forewarned about the coronavirus disease 2019 (COVID-19) pandemic environment fomenting the rising incidence of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). We performed a cross-sectional study of ALD at our liver transplantation (LT) center, located in the initial U.S. epicenter, New York City. Centered around the "stay at home" order date in New York state, March 22, 2020, we defined three time periods: "pre-COVID" (January 1, 2020-March 21, 2020), "COVID-quarantine" (March 22, 2020-April 22, 2020), and "declining-COVID" (April 23, 2020-August 25, 2020). We found a 62% increase in interhospital patient transfers for ALD from pre-COVID (20 of 93, 21%) to the declining-COVID period (43 of 127, 34%). Our inpatient liver census with ALD also increased: 38% pre-COVID, 45% COVID-quarantine, and 49% declining-COVID. Among 30 patients with severe alcoholic hepatitis (AH) not responding to medical therapy since March 22, 2020, 9 underwent early LT for AH (16% of the total number of early LT during our 8-year program). Three of 9 early-LT recipients reported specific COVID-related stressors. All 25 previous LT recipients with established abstinence pre-COVID maintained abstinence at follow-up visits during the declining-COVID period. Of the 6 recipients with sustained alcohol use within 6 months before March 22, 2020, half regained abstinence during the declining-COVID period. Our findings help confirm the predictions of rising AUD and ALD as an immediate consequence of the COVID-19 pandemic. This aftershock particularly affected ethnically diverse patients with ALD with high inpatient mortality, reflecting the disproportionate impact of COVID-19 on underserved and minority populations. Alcohol relapse did not occur in long-term early LT for AH recipients during the time of COVID-19. This lends further support to AH being a viable indication for LT, with recipients able to demonstrate ongoing resilience in the face of this unprecedented universal stressor.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

Coronavirus Disease 2019 Pandemic: Early Observations in Abdominal Organ Transplantation.

The recent COVID-19 outbreak has quickly become a worldwide pandemic emergency. The course of this pandemic is still unknown, with more than 6 million cases identified and over 370 000 deaths globally as of June 1, 2020. The uncertainty and anxiety during this period will have a detrimental effect on the global health system. The organ transplantation field has been negatively affected by the COVID-19 pandemic, especially in regions where the intensity of cases exceeds the available capacity of the health care resources. Recently, scattered data have been published in the English literature, mainly in case reports and letters to the editor, that describe the effect of COVID-19 on donors and recipients of abdominal solid organs. Our objective is to review and draw conclusions from these data.

Incidence and Outcomes of COVID-19 in Kidney and Liver Transplant Recipients With HIV: Report From the National HOPE in Action Consortium.

BACKGROUND: Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective. METHODS: Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States. RESULTS: Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/µL. Median CD4 pre-COVID-19 was 298 cells/µL, declining to <200 cells/µl in 6/7 with measurements on admission. Treatment included high-dose steroids (n = 6), tocilizumab (n = 3), remdesivir (n = 2), and convalescent plasma (n = 2). Four patients (36%) died. CONCLUSIONS: Within a national prospective cohort of kidney and liver transplant recipients with HIV, we report high mortality from COVID-19.

Evidence of potent humoral immune activity in COVID-19-infected kidney transplant recipients.

Whether kidney transplant recipients are capable of mounting an effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adaptive immune response despite chronic immunosuppression is unknown and has important implications for therapy. Herein, we analyzed peripheral blood cell surface and intracellular cytokine phenotyping by flow cytometry along with serum antibody testing in 18 kidney transplant recipients with active coronavirus disease 2019 (COVID-19) infection and 36 matched, transplanted controls without COVID-19. We observed significantly fewer total lymphocytes and fewer circulating memory CD4+ and CD8+ T cells in the COVID-19 subjects. We also showed fewer anergic and senescent CD8+ T cells in COVID-19 individuals, but no differences in exhausted CD8+ T cells, nor in any of these CD4+ T cell subsets between groups. We also observed greater frequencies of activated B cells in the COVID-19 patients. Sixteen of 18 COVID-19 subjects tested for anti-SARS-CoV-2 serum antibodies showed positive immunoglobulin M or immunoglobulin G titers. Additional analyses showed no significant correlation among immune phenotypes and degrees of COVID-19 disease severity. Our findings indicate that immunosuppressed kidney transplant recipients admitted to the hospital with acute COVID-19 infection can mount SARS-CoV-2-reactive adaptive immune responses. The findings raise the possibility that empiric reductions in immunosuppressive therapy for all kidney transplant recipients with active COVID-19 may not be required.

Kidney transplantation using lymphocyte depleting induction and standard maintenance immunosuppression at the height of the SARS-CoV-2 pandemic in New York City: A single-center experience.

BACKGROUND: Concerns have been raised regarding proceeding with kidney transplantation using standard immunosuppression in COVID-19 endemic areas. METHODS: We performed a single-center review of all adult kidney transplants performed during the COVID-19 pandemic in New York City. Patients were managed with standard immunosuppression protocols, including lymphocyte depleting induction and trough-guided tacrolimus. Retrospective data were collected for 3 months from the date of transplantation or until study conclusion (5/7/2020). The primary outcomes assessed included patient and allograft survival as well as COVID-19 related hospital readmission. RESULTS: 30 kidney transplants were performed during the height of the COVID-19 pandemic. After a median follow-up of 51.5 days, 93.3% of patients were alive with 100% death-censored allograft survival. 9 patients were readmitted to the hospital during the study period, 4 (13.3%) related to infection with COVID-19. Infections were mild in 3/4 patients, with one patient developing severe disease leading to respiratory failure. Patients readmitted with COVID-19 were numerically more likely to be African American, have a BMI > 30 kg/m2, have a lymphocyte count ≤ 300 cells/mL, and be on maintenance corticosteroids. CONCLUSIONS: Kidney transplantation in areas endemic to COVID-19 using standard induction and maintenance immunosuppression appears to be associated with a modest risk for severe COVID-19 related disease.

COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium.

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.