Optimal dose of rituximab in ABO-incompatible kidney transplantation in patients with low anti-A/B antibody titers: A single-center retrospective cohort study.

BACKGROUND: The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS: ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS: Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION: In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.

Comparison of Thymoglobulin and Grafalon as Induction Agents in Renal Transplantation: A Prospective Study.

BACKGROUND: Induction immunosuppression is used to reduce the incidence of acute rejection and prevent delayed graft function. The 2 rabbit anti-thymocyte globulins- thymoglobulin and Grafalon (ATG Fresenius) have been commonly used for induction immunosuppression and treatment of acute rejection in solid organ transplantation. There are very few studies comparing the efficacy and side effects of both the anti-thymocyte globulins therefore this prospective study comparing the 2 types of anti-thymocyte globulins would be of clinical interest. PATIENTS AND METHODS: This prospective single center study was conducted at Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India from April 2019 to June 2020. Sixty-two ABO-compatible renal transplant recipients were included in the study. They were divided in 2 groups of 31 patients each. One group received thymoglobulin (3 mg/kg) and the second group received Grafalon (6 mg/kg). All patients were followed up for 12 months and the 2 groups were compared for incidence of rejections, infections, graft function, patient survival, and graft survival. RESULTS: There was no significant difference in the incidence of rejections, infective episodes, graft function, posttransplant diabetes mellitus, graft survival and patient survival in thymoglobulin or Grafalon groups. The hematological parameters were similar in both groups at 7 days, 1 month, and 6 months of follow-up. The absolute lymphocyte count was significantly lower in the thymoglobulin group at 12 months posttransplant. CONCLUSIONS: Thymoglobulin and Grafalon were found to be equivalent in terms of safety and efficacy in short term, with no difference in rejections, infections, graft survival, or patient survival.

Impact of pandemic COVID-19 lockdown on penetrating keratoplasty patients.

Purpose: To study the impact of the COVID-19 lockdown on the regular follow-up of keratoplasty patients. Methods: This retrospective interventional case series included 30 patients who had immunological corneal endothelial rejection out of 190 patients who came for post-PKP follow-up between September 15, 2019, and September 30, 2020. The demographics, primary diagnosis, surgical technique, time of presentation, recovery of graft, associated ocular problems, and visual acuity at 1 month were analyzed. Forward stepwise (likelihood ratio) binary logistic regression was used to find significant variables. Results: The study population had 19 males (63.33%) and 11 females (36.67%). The mean age of the study group was 42.83 ± 18.89 (8-80) years. Of 30 patients, 19 (63.3%) presented before and 11 (36.7%) after the COVID-19 lockdown. Overall, 23 (77%) showed a reversal of graft rejection. Logistic regression showed that preoperative indications, large-sized grafts, and deep corneal vascularization were significant risk factors for non-resolution of graft rejection. It was noted that patients who presented to the hospital late had poor recovery (P = 0.002). The delay in the presentation was a significant risk factor for non-resolution of graft rejection (P < 0.01). Z-test for proportions revealed that the difference in the non-resolution of rejection on immediate or delayed treatment in patients presenting during lockdown (P = 0.002) was significant. Conclusion: This article is to highlight the impact of the COVID-19 lockdown on graft rejection recovery of PKP patients due to delays in follow-up. Early treatment helps in the recovery of graft transparency and the reversal of immunological graft rejection. Also, primary diagnosis, deep vascularization, and large-sized grafts were significant risk factors for non-resolution of graft rejection.

HIV in kidney transplantation.

PURPOSE OF REVIEW: The aim of this study was to describe recent developments in renal transplantation for HIV-positive recipients, especially the HIV Organ Policy Equity (HOPE) trial results. RECENT FINDINGS: HOPE trial data show that HIV-positive D+/R+ results are excellent and similar to D-/R+ in patients controlled on antiretroviral therapy (ART). Patients coinfected with hepatitis C or B virus now have effective treatment available. As pretransplant evaluation and post-transplant management is more complex in HIV-positive individuals early referral is important and coordination of evaluation and care with an infectious disease specialist is critical. HIV coordinated care services should be involved for best outcomes. HIV-positive renal transplant recipients have an increased risk of rejection and evidence suggests that standard lymphocyte depletion induction and maintenance immunosuppression be employed. Cardiovascular risk reduction and surveillance and attention to metabolic bone disease are important for HIV-positive renal transplant recipients. SUMMARY: HIV-positive to HIV-positive renal transplantation has been established as well tolerated and successful. Further efforts are needed to expand access to transplantation in this population. VIDEO ABSTRACT: http://links.lww.com/MOT/A29.

Safety of Antithymocyte Globulin Use in Kidney Graft Recipients During the COVID-19 Pandemic.

BACKGROUND There are many safety concerns regarding the use of antithymocyte globulin (ATG) in kidney transplant recipients (KTRs) during the ongoing COVID-19 pandemic. Hereby, we present our recent experience with ATG administration both as induction therapy and as an anti-rejection treatment. MATERIAL AND METHODS We retrospectively analyzed all patients transplanted during the first 12 months of the COVID-19 pandemic who were treated with thymoglobulin. The ATG dosing, lymphocyte number and percentage in blood smear, adverse effects (thrombocytopenia and infectious complications), and kidney graft function up to 12 months and patients' outcomes were analyzed and compared to KTRs who received basiliximab induction. RESULTS During pandemic, a total of 31 patients were treated with ATG and 59 received basiliximab. The median cumulative ATG doses were 275 (175-325) mg in the induction subgroup and 263 (200-275) mg in the anti-rejection treatment subgroup. Mild thrombocytopenia was noted in 7 (22.6%) and 13 (29.5%) patients, respectively. There were more infectious complications among patients treated with ATG as compared with the basiliximab subgroup (32.3 vs 10.2%, P<0.01), but there were similar incidence rates of thrombocytopenia. Kidney graft function up to 12 months after transplant was comparable (1.1 [1.0-1.9] vs 1.1 [1.0-1.4] mg/dl, respectively). CONCLUSIONS 1. ATG use in the induction protocol or as the anti-rejection treatment during the COVID-19 pandemic appears to be safe and the risk of adverse events is acceptable. 2. During the COVID-19 pandemic the necessary use of ATG should not be postponed, especially in KTRs with increased immunologic risk.

Impact of COVID-19 on Lung Allograft and Clinical Outcomes in Lung Transplant Recipients: A Case-control Study.

BACKGROUND: The impacts of COVID-19 on lung allograft function, rejection, secondary infection, and clinical outcomes in lung transplant recipients (LTRs) remain unknown. METHODS: A 1:2 matched case-control study was performed to evaluate rehospitalization, lung allograft function, and secondary infections up to 90 d after COVID-19 diagnosis (or index dates for controls). RESULTS: Twenty-four LTRs with COVID-19 (cases) and 48 controls were identified. Cases and controls had similar baseline characteristics and lung allograft function. LTRs with COVID-19 had higher incidence of secondary bacterial infection (29.2% versus 6.3%, P = 0.008), readmission (29.2% versus 10.4%, P = 0.04), and for-cause bronchoscopy (33.3% versus 12.5%, P = 0.04) compared with controls. At d 90, mortality in cases versus controls was 8.3% versus 2.1% (P = 0.21), incidence of invasive fungal infections in cases versus controls was 20.8% versus 8.3% (P = 0.13) and forced expiratory volume in 1 s (FEV1) decline ≥10% from baseline occurred in 19% of cases versus 12.2% of controls (P = 0.46). No acute cellular rejection, acute antibody-mediated rejection, or new donor-specific anti-HLA antibodies were observed among cases or controls within 90 d post index date. CONCLUSIONS: We found LTRs with COVID-19 were at risk to develop secondary infections and rehospitalization post COVID-19, compared with controls. While we did not observe post viral acute cellular rejection or antibody-mediated rejection, further studies are needed to understand if LTRs with COVID-19 who did not recover baseline lung function within 90 d have developed chronic lung allograft dysfunction stage progression.

Impact of a pharmacist-led, mHealth-based intervention on tacrolimus trough variability in kidney transplant recipients: A report from the TRANSAFE Rx randomized controlled trial.

PURPOSE: Nonadherence is a leading cause of death-censored allograft loss in kidney transplant recipients. Strong associations have tied tacrolimus intrapatient variability (IPV) to degree of nonadherence and high tacrolimus IPV to clinical endpoints such as rejection and allograft loss. Nonadherence is a dynamic, complex problem best targeted by multidimensional interventions, including mobile health (mHealth) technologies. METHODS: This was a secondary planned analysis of a 12-month, parallel, 2-arm, semiblind, 1:1 randomized controlled trial involving 136 adult kidney transplant recipients. The primary aims of the TRANSAFE Rx study were to assess the efficacy of a pharmacist-led, mHealth-based intervention in improving medication safety and health outcomes for kidney transplant recipients as compared to usual care. RESULTS: Patients were randomized equally to 68 patients per arm. The intervention arm demonstrated a statistically significant decrease in tacrolimus IPV over time as compared to the control arm (P = 0.0133). When analyzing a clinical goal of tacrolimus IPV of less than 30%, the 2 groups were comparable at baseline (P = 0.765), but significantly more patients in the intervention group met this criterion at month 12 (P = 0.033). In multivariable modeling, variables that independently impacted tacrolimus IPV included time, treatment effect, age, and warm ischemic time. CONCLUSION: This secondary planned analysis of an mHealth-based, pharmacist-led intervention demonstrated an association between the active intervention in the trial and improved tacrolimus IPV. Further prospective studies are required to confirm the mutability of tacrolimus IPV and impact of reducing tacrolimus IPV on long-term clinical outcomes.

Renal transplantation during the SARS-CoV-2 pandemic in the UK: Experience from a large-volume center.

There is uncertainty about the safety of kidney transplantation during the SARS-CoV-2 pandemic due to the risk of donor transmission, nosocomial infection and immunosuppression use. We describe organ donation and transplant practice in the UK and assess whether kidney transplantation conferred a substantial risk of harm. Data from the UK transplant registry were used to describe kidney donation and transplant activity in the UK, and a detailed analysis of short-term, single-center, patient results in two periods: during the pre-pandemic era from 30th December 2019 to 8th March 2020 ("Pre-COVID era") and the 9th March 2020 to 19th May 2020 ("COVID era"). Donor and recipient numbers fell by more than half in the COVID compared to the pre-COVID era in the UK, but there were more kidney transplants performed in our center (42 vs. 29 COVID vs. pre-COVID respectively). Overall outcomes, including re-operation, delayed graft function, primary non-function, acute rejection, length of stay and graft survival were similar between COVID and pre-COVID era. 6/71 patients became infected with SARS-CoV-2 but all were discharged without critical care requirement. Transplant outcomes have remained similar within the COVID period and no serious sequelae of SARS-CoV-2 infection were observed in the peri-transplant period.

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.

Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study.

Solid organ transplant recipients (SOTr) with coronavirus disease 2019 (COVID-19) are expected to have poorer outcomes compared to nontransplant patients because of immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 nonkidney organs) were compared to 100 consecutive hospitalized nontransplant controls. Twelve of 47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs 57% P = .0007), diabetes (66% vs 33% P = .0007), and hypertension (94% vs 72% P = .006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs 17%, P < .0001) was more frequent in SOTr. Primary composite outcome (escalation to intensive care unit, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs 48%, odds ratio [OR] 0.72 confidence interval [CI] [0.33-1.58] P = .42), despite more comorbidities in SOTr. Acute kidney injury requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] P = .007). Multivariate analysis demonstrated that increasing age and clinical severity were associated with mortality. Transplant status itself was not associated with mortality.

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.

Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.

Immune monitoring facilitates the clinical decision in multifocal COVID-19 of a pancreas-kidney transplant patient.

The optimal management in transplant recipients with coronavirus disease 2019 (COVID-19) remains uncertain. The main concern is the ability of immunosuppressed patients to generate sufficient immunity for antiviral protection. Here, we report on immune monitoring facilitating a successful outcome of severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated pneumonia, meningoencephalitis, gastroenteritis, and acute kidney and pancreas graft failure in a pancreas-kidney transplant recipient. Despite the very low numbers of circulating B, NK, and T cells identified in follow-up, a strong SARS-CoV-2 reactive T cell response was observed. Importantly, we detected T cells reactive to Spike, Membrane, and Nucleocapsid proteins of SARS-CoV-2 with majority of T cells showing polyfunctional proinflammatory Th1 phenotype at all analyzed time points. Antibodies against Spike protein were also detected with increasing titers in follow-up. Neutralization tests confirmed their antiviral protection. A correlation between cellular and humoral immunity was observed underscoring the specificity of demonstrated data. We conclude that analyzing the kinetics of nonspecific and SARS-CoV-2-reactive cellular and humoral immunity can facilitate the clinical decision on immunosuppression adjustment and allow successful outcome as demonstrated in the current clinical case. Although the antiviral protection of the detected SARS-CoV-2-reactive T cells requires further evaluation, our data prove an ability mounting a strong SARS-CoV-2-reactive T cell response with functional capacity in immunosuppressed patients.

COVID-19 in lung transplant recipients: A single center case series from New York City.

There are limited data describing COVID-19 in lung transplant recipients. We performed a single center, retrospective case series study of lung transplant patients followed by the Columbia Lung Transplant program who tested positive for SARS-CoV-2 between March 19 and May 19, 2020. Thirty-two lung transplant patients developed mild (16%), moderate (44%), or severe (41%) COVID-19. The median age of patients was 65 years, and the median time from lung transplant was 5.6 years. Symptoms included cough (66%), dyspnea (50%), fever (47%), and gastrointestinal upset (44%). Patients received hydroxychloroquine (84%), azithromycin (75%), augmented steroids (44%), tocilizumab (19%), and remdesivir (9%). Eleven patients (34%) died at a median time of 14 days from admission. Complications during admission included: acute kidney injury (63%), transaminitis (31%), shock (31%), acute respiratory distress syndrome (25%), neurological events (25%), arrhythmias (22%), and venous thromboembolism (9%). Compared to patients with moderate COVID-19, patients with severe COVID-19 had higher peak white blood cell counts (15.8 vs 7 × 103 /uL, P = .019), C-reactive protein (198 vs. 107 mg/L, P = .010) and D-dimer (8.6 vs. 2.1 ug/mL, P = .004) levels, and lower nadir lymphocyte counts (0.09 vs. 0.4 × 103 /uL, P = .006). COVID-19 is associated with severe illness and a high mortality rate in lung transplant recipients.

Kidney allograft recipients, immunosuppression, and coronavirus disease-2019: a report of consecutive cases from a New York City transplant center.

BACKGROUND: Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies. METHODS: We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate. RESULTS: Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients. CONCLUSIONS: Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.

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.

Low rate of COVID-19 pneumonia in kidney transplant recipients-A battle between infection and immune response?

BACKGROUND: With COVID-19 pandemic, concerns about kidney transplant recipients are rising. However, the incidence, clinical course, outcome, and predictive factors of disease severity are obscured. METHODS: We describe clinical and laboratory manifestations, radiologic findings, clinical course, and finally outcome of kidney transplant recipients with COVID-19 pneumonia. RESULTS: Of 2493 kidney transplant recipients under follow-up in our clinic, 19 cases (4 cases diagnosed based on radiologic findings) were admitted. The mean age of patients was 47.6 ± 12.4 years, and the mean time from transplantation was 115.6 ± 70.3 months. Lymphopenia and eosinopenia were 84.2% and 78.9%, respectively. Nine patients did not survive the hospital course. History of acute rejection during the past 12 months, diabetes, higher N/L ratio, lower platelet count, elevated N/L x CRP, higher levels of LDH, positive D-dimer, higher troponin, and prolonged PT were associated with mortality. Among patients with positive COVID-19 test, history of acute rejection, low platelet count, and positive D-dimer were associated with poor outcome. Treatment with cyclosporine was associated with better clinical outcome. CONCLUSIONS: Low rate of admission in transplant recipients specially in the very first years of transplantation might be due to protective effects of immunosuppressive agents against cytokine storm or modification of immunity function. We suggest evaluation of T-cell number, function, and cytokine profile as a guide to manage COVID-19 mainly in patients with higher risk of mortality.

COVID-19 in solid organ transplant recipients: Dynamics of disease progression and inflammatory markers in ICU and non-ICU admitted patients.

BACKGROUND: COVID-19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ transplant (SOT) recipients are limited. METHODS: We examined the electronic medical records of all SOT recipients with COVID-19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients. RESULTS: Of 52 COVID-19-positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty-nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co-infections occurred in 45% in ICU vs 5% in non-ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died. CONCLUSIONS: Our data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID-19 compared to data in the general population of patients with COVID-19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.