Tocilizumab use in Kidney Transplant Patients with COVID-19

A potential benefit of immunomodulatory agents such as tocilizumab (TCZ) has been reported in patients with coronavirus disease 2019 (COVID-19) and severe pulmonary involvement. However, this therapy has been scarcely studied in kidney transplant (KT) recipients. Herein, we describe the clinical course and outcome of 10 KT patients with severe COVID-19 that were treated with TCZ. Mean age of the study group was 54 ± 10 years (70% females), and 30% of the cases were within 6 months from transplant. Mycophenolate mofetil was discontinued in all cases upon admission, whereas baseline steroids were maintained and tacrolimus dose was reduced. Initial treatment included hydroxychloroquine, antibiotics, and prophylactic anticoagulation. Before treatment with TCZ, 3 patients were receiving high-flow oxygen, 4 patients low-flow oxygen and 1 case non-invasive ventilation. All patients received a single dose of intravenous TCZ within a mean time of 7 ± 4 days since admission. During a median follow-up of 16 days (IQR: 10-29), 7 patients (70%) gradually improved and were finally discharged while three cases (30%) did not exhibited clinical improvement and ultimately died. In conclusion, although treatment with TCZ could be associated with improved clinical outcomes in a subset of KT recipients with COVID-19, further studies are warranted before drawing firm conclusions.     

Global Impact of the COVID-19 Pandemic on Solid Organ Transplant

BackgroundCOVID-19 has drastically affected transplant services, but there is limited understanding of the discrepancy of COVID-19 effects on various regions of the world.MethodsWe have explored the Global Observatory for Organ Donation and Transplantation data for assessing the transplant number changes between the calendar year 2019 (n = 157,301) and 2020 (129,681).ResultsThere was a disproportionate impact of COVID-19 on different areas of the world. Globally, there was a decline of 17.5%, in which deceased donation, kidney (20.9%), pancreas (16.2%), lung (12.7%), liver (11.3%), and heart (8%) transplant declined disproportionally in different regions of the world. The pandemic affected almost all geographic regions and nations, but China and the United States were mostly able to recover from the initial halt of the transplant practices by the pandemic so that there was a cumulative increase in transplant numbers.ConclusionsOur data show that developing nations lagged behind, whereas developed nations have been able to recover their transplantation programs during the pandemic. Further policy making and preparedness is required to safeguard the most vulnerable areas of the world to minimize the impact of any future pandemic on transplantation practices.     

Pulmonary Hypertension among Patients on Dialysis and Kidney Transplant Recipients

Pulmonary arterial hypertension (PAH) is a serious cardiac complication among patients with end-stage renal disease (ESRD). We investigated pulmonary hypertension and its associated factors among patients who were on chronic dialysis and kidney transplant recipients. One hundred-eighty patients in three groups of hemodialysis (HD), peritoneal dialysis (PD), and kidney transplant were studied. Demographic and clinical characteristics and echocardiographic findings were evaluated. A multivariable linear regression model was used to find factors associated with pulmonary artery pressure. The mean age of participants was 50.3 ± 15.5 years and 63.9% were male. We found pulmonary hypertension (mean pulmonary artery pressure >25 mmHg) in 31.6%, 8.3%, and 5% of the patients on HD, PD, and transplant recipients, respectively (p < 0.001). In multivariate analyses, being on HD (B = 5.276, confidence interval [CI] 95%: 1.211–9.341), age (B = –0.319, CI 95%: –0.501 to –0.138), smoking (B = 11.631, CI 95%: 1.847–21.416), systolic cardiac dysfunction (B = 6.313, CI 95%: 3.073–9.554), and diastolic cardiac dysfunction (B = 5.227, CI 95%: 1.176–9.277) were associated with systolic pulmonary artery pressure. These results showed that pulmonary hypertension is a frequent cardiac complication among patients with ESRD, and the type of renal replacement therapy (HD), systolic and diastolic cardiac dysfunction, and smoking are associated with increased pulmonary artery pressure. Further studies with larger sample sizes and also prospective studies are recommended in this regard.     

Immunosuppressive Medication Adherence in Kidney Transplant Recipients During the COVID-19 Pandemic: A Cross-Sectional Study in Hong Kong

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has put an enormous burden on health care systems worldwide. Limited access to medical care and fear of increased infective risks due to the use of immunosuppressive medication (IM) have increased concerns about IM adherence in kidney transplant recipients (KTRs). The aim of this study was to determine the various dimensions of IM nonadherence in KTRs during the COVID-19 pandemic.MethodsThis was a single-center, cross-sectional study using a convenient sampling approach. KTRs with follow-up in Queen Elizabeth Hospital, Hong Kong between May 1, 2020 and September 30, 2020, were invited to complete a self-reported questionnaire on IM adherence. The sociodemographic factors associated with IM adherence were extracted from medical records.ResultsOverall, 210 patients completed the questionnaires. The overall IM nonadherence rate was 35.2% in the 4 weeks before survey completion. None of the patients stopped taking IMs without instructions from their health care providers. The most common pattern of IM nonadherence was timing adherence (n = 63; 30.1%), followed by dose-skipping item. Among the different sociodemographic factors studied, only marital status was an independent risk factor of IM nonadherence (odds ratio, 1.97; 95% confidence interval, 1.04-3.72; P = .03).ConclusionsThe impact of COVID-19 on IM adherence in KTRs was not significant. All the patients continued their IM despite of the pandemic. Good family support can have a positive influence on treatment adherence in KTRs during the COVID-19 pandemic.     

Retrospective Evaluation of COVID-19 Infection and COVID-19 Vaccines in Heart Transplant Patients

BackgroundPatients who have performed solid organ transplantation in terms of COVID-19 infection are included in the high-risk group. In this study, it was aimed to evaluate the relationship between vaccination and retrospective evaluation of 32 patients who underwent a heart transplant in the clinic and tested positive for SARS-CoV-2 polymerase chain reaction.MethodsIn this study, demographic characteristics of the cases, comorbidities, timing of heart transplantation, immunosuppressive treatments, symptoms of COVID-19 infection, lung imaging findings, follow-up (outpatient/inpatient), treatments, 1-month mortality, and vaccination histories against COVID-19 infection were evaluated. The data obtained from the study were analyzed with SPSS version 25.0.ResultsThe 3 most common symptoms are cough (37.5%), myalgia (28.1%), and fever (21.8%). COVID-19 infection was severe in 6.2% of the patients, moderate in 37.5%, and mild in 56.2%. Hospitalization was required in 5 patients (15.6%, 1 in the intensive care unit), and the other patients were followed up as an outpatient. Severe COVID-19 infection was seen more in 33% of unvaccinated patients; 93.5% were vaccinated. Nineteen patients (68%) were vaccinated before COVID-19 infection. Our patients received the CoronoVac (Sinovac, China) vaccine.ConclusionCOVID-19 infection is more likely to be severe and mortal in patients with heart transplant recipients. It is also crucial to comply with preventive measures other than immunization in this group of patients. This study is the largest series investigating COVID-19 infection in heart transplant recipient patients in our country.     

Identification of Autoreactive Lymphocytotoxic Antibodies in Sensitised Dialysis and Kidney Transplant Patients

Autoreactive lymphocytotoxic antibodies, which have been foundin sensitised dialysis patients, are generally not consideredto be harmful to a renal allograft. In this work the presenceof such autoreactive antibodies was investigated in the followinggroups of sensitised end-stage renal disease patients: (a) dialysispatients waiting for a first kidney transplant, (b) kidney transplantedpatients, and (c) dialysis patients with a previous failed graft.Only sera from the above patients which showed high reactivity(>30%) against peripheral blood lymphocytes of a random cellpanel (R-PBL), were screened for the presence of autoreactivelymphocytotoxic antibodies, by testing at different temperaturesagainst autologous T lymphoblasts (PHA-ATL) and EBV-inducedautologous B lymphoblasts (EBV-ABL). The results showed that both bood transfusions, and viral infectionssuch as cytomegalovirus (CMV), correlated with the presenceof autoreactive antibodies, and that in addition, by using PHA-ATLand /or EBV-ABL as absorbing reagents, it was possible to removethe antibodies. These absorption procedures allowed the identificationof the presence of autoreactive antibodies alone or in combinationwith other alloantibodies.     

COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity

BackgroundThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients.MethodsData were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test.ResultsSixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored.ConclusionsSevere disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.     

Safety and Tolerability of mRNA COVID-19 Vaccines in Kidney Transplant Recipients

BackgroundCOVID-19 mRNA vaccines have demonstrated excellent short-term safety in phase 3 trials. However, no kidney transplant recipients (KTR) were included. The aim of the study was to assess the safety and tolerability of COVID-19 mRNA vaccines in KTR.Materials and MethodsA longitudinal controlled study was conducted in 300 KTR and 143 control patients (CRL) without chronic kidney disease who had received 2-dose vaccinations with the mRNA vaccine. Solicited local and systemic reactogenicity and unsolicited adverse events were assessed with a standardized questionnaire. The toxicity grading scales were derived from the FDA guidelines.ResultsKTR (62.7% men) with a median (interquartile range) age of 53 (41-63) and transplant vintage of 7.25 (3-13) years did not differ with respect to age and sex distribution from CRL. One hundred percent CRL and 83.3% KTR were vaccinated with BNT162b2 (BionTech/Pfizer); 16.7% KTR received mRNA-1273 (Moderna) vaccine. Any local reactions were present in 84.7% (first dose) and 65.3% (second dose) KTR vs 67.1% and 60.1% CRL within 7 days after the vaccination. Any systemic reactions were reported by 26.7% (first dose) and 20.9% (second dose) KTR vs 24.7 and 35.7% CRL. The most common systemic reactions in KTR were fatigue, headache and myalgia. No serious adverse events were observed. Many systemic reactions were observed less frequently in KTR than CRL. Younger KTR (<54 years) reported any local and any systemic reactions significantly more frequently than older patients.ConclusionmRNA COVID-19 vaccines are safe and well-tolerated by KTR. The results may resolve patients' doubts and reduce their vaccine hesitancy.     

Significance of PPD Test for the Relationship Between BCG Vaccine and COVID-19 in Patients on Kidney Transplant Waiting List

BackgroundThe aim of this study was to determine the relationship between purified protein derivative of tuberculin (PPD) values, an indicator of BCG protection, and COVID-19 disease in patients with end-stage renal disease (ESRD) on the kidney transplant waiting list.MethodsAge, sex, dialysis type, ERSD etiologies, and PPD values of patients on the renal transplant waiting list were recorded. SARS-CoV-2 PCR data, whether the patients were previously infected with the virus, and, if infected, the severity of the disease were noted. Data were statistically compared.ResultsPCR of 87 (47.02%) of 185 patients were studied; 107 of the patients were male and 78 were female, with a mean age of 52.8 years. The test result was positive for 28 patients. Of the patients for whom PCR was studied, 41 had a negative PPD result, while 46 had a positive PPD result. There was no correlation with SARS-CoV-2 PCR positivity in patients with a PPD ≤ 5 mm and > 5 mm. However, patients with pneumonic infiltration who required hospitalization had a significantly higher PPD value.ConclusionsThe PPD measurement, which is an indicator of BCG protection, might be a significant parameter for predicting the course of the disease in SARS-CoV-2 pneumonia.     

Chronic Active Antibody-Mediated Rejection Following COVID-19 Infection in a Kidney Transplant Recipient: A Case Report

Kidney transplant recipients who develop coronavirus disease 2019 (COVID-19) are at increased risk of life-threatening illness, which often requires reducing immunosuppression despite the potential risk of causing an allograft rejection. Herein, we describe the clinical presentation and course of a kidney transplant recipient who acquired COVID-19 and was hospitalized with severe symptoms and hypoxemia. Upon admission, the patient was found to have elevated de novo donor-specific antibodies (DSA) yielding a positive cytotoxicity crossmatch and concurrent elevated plasma donor-derived cell-free DNA (dd-cfDNA) level, indicating a possible ongoing rejection despite improvement in his serum creatinine. Because of persistent positive COVID-19 tests and stable serum creatinine, a kidney allograft biopsy was initially deferred and his dd-cfDNA and DSA were monitored closely postdischarge. Three months later, because of persistent elevated dd-cfDNA and positive DSA, a kidney allograft biopsy was performed, which showed chronic active antibody-mediated rejection. Accordingly, the patient was treated with intravenous immunoglobulin and his maintenance immunosuppressive regimen was increased.