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1.
Curr Opin Organ Transplant ; 27(6): 530-534, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2051719

ABSTRACT

PURPOSE OF REVIEW: Adequately managing a complex medical regimen is paramount to the success of organ transplants. When patients stray from their prescribed medical regimen posttransplant, graft rejection, and death can occur. Predictors of adherence have been studied for many years, and various factors have been identified as contributing to adequate or poor adherence. Both demographic and personal characteristics have been associated with adherence behavior. However, recent developments, such as the COVID-19 pandemic, increased use of mobile health interventions, and use of medical biomarkers have affected the way adherence is measured and applied. RECENT FINDINGS: The COVID-19 pandemic affected patients' comfort with accessing outpatient care and created a wider use of telehealth services. Measurement of adherence through serum lab levels continues to be reviewed as a potential objective assessment of adherence. Psychosocial factors continue to be identified as major contributors to nonadherence. SUMMARY: Adherence to antirejection medication, lab work, appointments, and exercise and dietary instructions remains critical to the health of the transplant patient. It is critical that providers involved in the selection process and posttransplant treatment of these patients remain well informed of potential new factors affecting adherence.


Subject(s)
COVID-19 , Immunosuppressive Agents , Humans , Immunosuppressive Agents/adverse effects , Medication Adherence , COVID-19/epidemiology , Pandemics , Graft Rejection/prevention & control
2.
Transplantation ; 106(11): 2200-2204, 2022 11 01.
Article in English | MEDLINE | ID: covidwho-1973353

ABSTRACT

BACKGROUND: Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs). METHODS: ingle-center prospective cohort study' all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included. RESULTS: Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin-based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines' and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir' and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity. CONCLUSIONS: Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.


Subject(s)
COVID-19 , Kidney Transplantation , Adult , Humans , COVID-19/drug therapy , SARS-CoV-2 , Basiliximab , Kidney Transplantation/adverse effects , Tacrolimus/adverse effects , Graft Rejection/prevention & control , Prospective Studies , Immunosuppressive Agents/adverse effects , Transplant Recipients , Methylprednisolone
4.
Am J Transplant ; 22(7): 1884-1892, 2022 07.
Article in English | MEDLINE | ID: covidwho-1956680

ABSTRACT

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p = .016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.


Subject(s)
Lung Transplantation , Tacrolimus , Abatacept/therapeutic use , Antilymphocyte Serum/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/prevention & control , Graft Survival , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Lung Transplantation/adverse effects , Mycophenolic Acid/therapeutic use , Pilot Projects , Prednisone
6.
Front Immunol ; 13: 888385, 2022.
Article in English | MEDLINE | ID: covidwho-1924104

ABSTRACT

Objective: This is the first systematic review and meta-analysis to determine the factors that contribute to poor antibody response in organ transplant recipients after receiving the 2-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Method: Data was obtained from Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBM). Studies reporting factors associated with antibody responses to the 2-dose SARS-CoV-2 vaccine in solid organ transplant recipients were included in our study based on the inclusion and exclusion criteria. Two researchers completed the literature search, screening, and data extraction. Randomized models were used to obtain results. Egger's test was performed to determine publication bias. Sensitivity analysis was performed to determine the stability of the result. The heterogeneity was determined using the Galbraith plot and subgroup analysis. Results: A total of 29 studies were included in the present study. The factors included living donor, BNT162b2, tacrolimus, cyclosporine, antimetabolite, mycophenolic acid (MPA) or mycophenolate mofetil (MMF), azathioprine, corticosteroids, high-dose corticosteroids, belatacept, mammalian target of rapamycin (mTOR) inhibitor, tritherapy, age, estimated glomerular filtration rate (eGFR), hemoglobin, and tacrolimus level were significantly different. Multivariate analysis showed significant differences in age, diabetes mellitus, MPA or MMF, high-dose corticosteroids, tritherapy, and eGFR. Conclusion: The possible independent risk factors for negative antibody response in patients with organ transplants who received the 2-dose SARS-CoV-2 vaccine include age, diabetes mellitus, low eGFR, MPA or MMF, high-dose corticosteroids, and triple immunosuppression therapy. mTOR inhibitor can be a protective factor against weak antibody response. Systematic Review Registration: PROSPERO, identifier CRD42021257965.


Subject(s)
COVID-19 , Diabetes Mellitus , Kidney Transplantation , Adult , Antibody Formation , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Diabetes Mellitus/drug therapy , Graft Rejection/prevention & control , Humans , Kidney Transplantation/methods , Mycophenolic Acid , Risk Factors , SARS-CoV-2 , TOR Serine-Threonine Kinases , Tacrolimus
9.
Transplant Proc ; 54(6): 1557-1560, 2022.
Article in English | MEDLINE | ID: covidwho-1852177

ABSTRACT

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a significant impact on communities and health systems. New antiviral medications against this disease have not been properly tested yet, and their efficiency, side effects, and drug-drug interactions are not entirely known. Organ transplant recipients receive immunosuppressive medications such as tacrolimus to prevent graft rejection. Tacrolimus is metabolized by the cytochrome P450 3A4 enzyme system. Many medications can either induce or inhibit this enzyme and affect the level. Awareness of possible drug-drug interactions is vital because tacrolimus levels should be kept within a specific narrow range determined by the recipient's immunologic risk. Underexposure increases the risk of graft rejection, whereas overexposure may lead to adverse effects. Paxlovid, a novel antiviral medication approved for emergency use to treat SARS-CoV-2, is a combination of nirmatrelvir and ritonavir, a cytochrome P450 34A inhibitor. In this case report, we present a case of a kidney transplant patient receiving tacrolimus treated with Paxlovid, leading to an abruptly high tacrolimus level, significant symptoms, treatment interruption, and acute kidney injury. We conclude that the drug-drug interaction between Paxlovid and tacrolimus is indeed robust and noteworthy and leads to high tacrolimus levels and its metabolites, adverse effects, and acute kidney injury. Physicians managing immunocompromised patients receiving tacrolimus should be aware of this significant drug-drug interaction and consider other options or reduction of daily tacrolimus dose during treatment in addition to timely monitoring of both tacrolimus levels and serum creatinine. Consulting with the transplant pharmacist is foremost in alerting for these interactions.


Subject(s)
Acute Kidney Injury , COVID-19 , Kidney Transplantation , Acute Kidney Injury/chemically induced , Antiviral Agents/adverse effects , COVID-19/drug therapy , Creatinine , Drug Combinations , Drug Interactions , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Lactams , Leucine , Nitriles , Proline , Ritonavir/adverse effects , SARS-CoV-2 , Tacrolimus/adverse effects
11.
Clin Transplant ; 36(7): e14697, 2022 07.
Article in English | MEDLINE | ID: covidwho-1840388

ABSTRACT

The COVID-19 pandemic initially brought forth considerable challenges to the field of heart transplantation. To prevent the spread of the virus and protect immunocompromised recipients, our center made the following modifications to post-transplant outpatient management: eliminating early coronary angiograms, video visits for postoperative months 7, 9, and 11, and home blood draws for immunosuppression adjustments. To assess if these changes have impacted patient outcomes, the current study examines 1-year outcomes for patients transplanted during the pandemic. Between March and September 2020, we assessed 50 heart transplant patients transplanted during the pandemic. These patients were compared to patients who were transplanted during the same months between 2011 and 2019 (n = 482). Endpoints included subsequent 1-year survival, freedom from cardiac allograft vasculopathy, any-treated rejection, acute cellular rejection, antibody-mediated rejection, nonfatal major adverse cardiac events (NF-MACE), and hospital and ICU length of stay. Patients transplanted during the pandemic had similar 1-year endpoints compared to those of patients transplanted from years prior apart from 1-year freedom from NF-MACE which was significantly higher for patients transplanted during the pandemic. Despite necessary changes being made to outpatient management of heart transplant recipients, heart transplantation continues to be safe and effective with similar 1-year outcomes to years prior.


Subject(s)
COVID-19 , Heart Transplantation , COVID-19/epidemiology , Graft Rejection/etiology , Graft Rejection/prevention & control , Humans , Pandemics , Retrospective Studies , Transplant Recipients
13.
Transplant Proc ; 54(6): 1572-1574, 2022.
Article in English | MEDLINE | ID: covidwho-1799689

ABSTRACT

Management of COVID-19 in lung transplant recipients is challenging. We report a case of a 71-year-old male who underwent bilateral lung transplantation with an unexpected case of COVID-19. The patient had been fully vaccinated. The patient and donor tested negative for pretransplant COVID-19. On routine bronchoscopy on day 1 after transplant, the COVID-19 test was positive. Mycophenolic mofetil and the second dose of basiliximab were skipped, but tacrolimus and prednisone were continued. He was treated with casirivimab/imdevimab and remdesivir. He was discharged on day 14 and has had no episodes of acute rejection during the 3 months.


Subject(s)
COVID-19 , Kidney Transplantation , Lung Transplantation , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Basiliximab , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/adverse effects , Lung Transplantation/adverse effects , Male , Mycophenolic Acid/therapeutic use , Prednisone/therapeutic use , Tacrolimus/therapeutic use
14.
Curr Opin Organ Transplant ; 27(1): 64-69, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1794983

ABSTRACT

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.


Subject(s)
HIV Infections , Hepatitis C , Kidney Transplantation , Graft Rejection/epidemiology , Graft Rejection/prevention & control , HIV Infections/complications , HIV Infections/diagnosis , HIV Infections/drug therapy , Hepacivirus , Humans , Kidney Transplantation/adverse effects , Transplant Recipients
15.
BMJ Open ; 12(4): e061864, 2022 04 15.
Article in English | MEDLINE | ID: covidwho-1794490

ABSTRACT

INTRODUCTION: Regulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the clinical setting. Phase 1 clinical trials have shown Treg therapy to be safe and feasible in clinical practice. Here we describe a protocol for the TWO study, a phase 2b randomised control trial of Treg therapy in living donor kidney transplant recipients that will confirm safety and explore efficacy of this novel treatment strategy. METHODS AND ANALYSIS: 60 patients will be randomised on a 1:1 basis to Treg therapy (TR001) or standard clinical care (control). Patients in the TR001 arm will receive an infusion of autologous polyclonal ex vivo expanded Tregs 5 days after transplantation instead of standard monoclonal antibody induction. Maintenance immunosuppression will be reduced over the course of the post-transplant period to low-dose tacrolimus monotherapy. Control participants will receive a standard basiliximab-based immunosuppression regimen with long-term tacrolimus and mycophenolate mofetil immunosuppression. The primary endpoint is biopsy proven acute rejection over 18 months; secondary endpoints include immunosuppression burden, chronic graft dysfunction and drug-related complications. ETHICS AND DISSEMINATION: Ethical approval has been provided by the National Health Service Health Research Authority South Central-Oxford A Research Ethics Committee (reference 18/SC/0054). The study also received authorisation from the UK Medicines and Healthcare products Regulatory Agency and is being run in accordance with the principles of Good Clinical Practice, in collaboration with the registered trials unit Oxford Clinical Trials Research Unit. Results from the TWO study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses. TRIAL REGISTRATION NUMBER: ISRCTN: 11038572; Pre-results.


Subject(s)
Kidney Transplantation , T-Lymphocytes, Regulatory , Graft Rejection/prevention & control , Humans , Immunosuppression Therapy , Immunosuppressive Agents/adverse effects , Kidney Transplantation/methods , Living Donors , Randomized Controlled Trials as Topic , State Medicine , Tacrolimus/therapeutic use
17.
Am J Transplant ; 22(8): 2083-2088, 2022 08.
Article in English | MEDLINE | ID: covidwho-1741322

ABSTRACT

Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID-19. The objective was to evaluate outcomes among SOTR and describe the drug-drug interaction of NR. This is an IRB-approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID-19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre- and post-NR were 7.4 ng/ml (IQR, 6.6-8.6) and 5.2 (IQR, 3.6-8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post-NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re-introduce CNI after the NR course is complete.


Subject(s)
COVID-19 , Lactams , Leucine , Nitriles , Proline , Ritonavir , Transplant Recipients , Adult , COVID-19/drug therapy , Calcineurin Inhibitors/therapeutic use , Cyclosporine/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Lactams/therapeutic use , Leucine/therapeutic use , Nitriles/therapeutic use , Organ Transplantation , Proline/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use , Sirolimus/therapeutic use , Tacrolimus/therapeutic use
18.
EBioMedicine ; 73: 103679, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1595805

ABSTRACT

BACKGROUND: The immunogenicity of a two-dose mRNA COVID-19 vaccine regimen is low in kidney transplant (KT) recipients. Here, we provide a thorough assessment of the immunogenicity of a three-dose COVID-19 vaccine regimen in this population. METHODS: We performed a prospective longitudinal study in sixty-one KT recipients given three doses of the BNT162b2 COVID-19 vaccine. We performed semi-structured pharmacovigilance interviews and monitored donor-specific antibodies and kidney function. We compared levels of anti-spike IgG, pseudo-neutralization activity against vaccine homologous and heterologous variants, frequency of spike-specific interferon (IFN)-γ-secreting cells, and antigen-induced cytokine production 28 days after the second and third doses. FINDINGS: Reactions to vaccine were mild. One patient developed donor-specific anti-HLA antibodies after the second dose which could be explained by non-adherence to immunosuppressive therapy. Spike-specific IgG seroconversion raised from 44·3% (n=27) after the second dose to 62·3% (n=38) after the third dose (p<0·05). The mean level of spike-specific IgG increased from 1620 (SD, 3460) to 8772 (SD, 16733) AU/ml (p<0·0001). Serum neutralizing activity increased after the third dose for all variants of concern tested including the Delta variant (p<0·0001). The frequency of spike-specific IFN-γ-secreting cells increased from 19·9 (SD, 56·0) to 64·0 (SD, 76·8) cells/million PBMCs after the third dose (p<0·0001). A significant increase in IFN-γ responses was also observed in patients who remained seronegative after three doses (p<0·0001). INTERPRETATION: A third dose of the BNT162b2 vaccine increases both cross-variant neutralizing antibody and cellular responses in KT recipients with an acceptable tolerability profile. FUNDING: Nice University Hospital, University Cote d'Azur.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19/immunology , Kidney Transplantation , Aged , Antibodies, Neutralizing/blood , Autoantibodies/blood , /adverse effects , COVID-19/prevention & control , COVID-19/virology , Female , Graft Rejection/prevention & control , HLA Antigens/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunosuppressive Agents/therapeutic use , Interferon-gamma/metabolism , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Longitudinal Studies , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology
19.
Indian J Ophthalmol ; 70(1): 319-321, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1597240

ABSTRACT

Endothelial rejection has been described following both m-RNA and vector-based vaccines for COVID-19. There is one case report of a stromal rejection described following influenza vaccination. We report a case of stromal rejection following vector-based COVID-19 vaccination, which might be the first case reported so far.


Subject(s)
COVID-19 Vaccines , COVID-19 , ChAdOx1 nCoV-19 , Graft Rejection/diagnosis , Graft Rejection/prevention & control , Humans , Keratoplasty, Penetrating/adverse effects , SARS-CoV-2
20.
Eye Contact Lens ; 47(11): 625-628, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1566082

ABSTRACT

ABSTRACT: Owing to its rapid development, short-term and long-term effects of the COVID-19 vaccine are still not well understood. This case report highlights bilateral corneal endothelial graft rejection after administration of the Pfizer COVID-19 vaccine. A 73-year-old woman with bilateral Descemet stripping endothelial keratoplasty presented with bilateral decreased visual acuity, ocular pain, and photophobia after her second dose of the Pfizer-BioNTech COVID-19 vaccine. Two weeks after vaccine administration, the uncorrected visual acuity was 20/70 and 20/40. Central corneal thickness as measured by ultrasound was 809 and 825 µm and by Scheimfplug imaging was 788 and 751 µm at the pupil center. Slit-lamp biomicroscopy revealed quiet conjunctiva and sclera but was significant for thickened corneas with Descemet folds in both eyes. The patient was instructed to use prednisolone acetate 1% every 1 to 2 hours with Muro ointment at bedtime.


Subject(s)
COVID-19 , Corneal Diseases , Descemet Stripping Endothelial Keratoplasty , Aged , COVID-19 Vaccines , Corneal Diseases/surgery , Descemet Membrane , Endothelium, Corneal , Female , Graft Rejection/prevention & control , Humans , Retrospective Studies , SARS-CoV-2
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