scholarly journals Severe COVID-19 by SARS-CoV-2 Lineage B.1.1.7 in Vaccinated Solid-Organ Transplant Recipients: New Preventive Strategies Needed to Protect Immunocompromised Patients

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 806
Author(s):  
Daniela Loconsole ◽  
Emma Diletta Stea ◽  
Anna Sallustio ◽  
Giulia Fontò ◽  
Virginia Pronzo ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Vaccination Strategy ◽  
High Viral Load ◽  
Heart Transplant Recipient ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Protein Subunit

Background: Solid-organ transplant (SOT) recipients are at a high risk of severe COVID-19, and are priority for vaccination. Here, we describe three cases of severe COVID-19 caused by SARS-CoV-2 B.1.1.7 lineage in vaccinated SOT recipients. Methods: Three SOT patients were hospitalized in the Policlinico Hospital of Bari (southern Italy) and underwent nasopharyngeal swabs for molecular detection of SARS-CoV-2 genes and spike protein mutations by real-time PCR. One sample was subjected to whole-genome sequencing. Results: One patient was a heart transplant recipient and two were kidney transplant recipients. All were hospitalized with severe COVID-19 between March and May 2021. Two patients were fully vaccinated and one had received only one dose of the BNT162b2 mRNA vaccine. All the patients showed a high viral load at diagnosis, and molecular typing revealed the presence of B.1.1.7 lineage SARS-CoV-2. In all three cases, prolonged viral shedding was reported. Conclusions: The three cases pose concern about the role of the B.1.1.7 lineage in severe COVID-19 and about the efficacy of COVID-19 vaccination in immunocompromised patients. Protecting immunocompromised patients from COVID-19 is a challenge. SOT recipients show a suboptimal response to standard vaccination, and thus, an additive booster or a combined vaccination strategy with mRNA, protein/subunit, and vector-based vaccines may be necessary. This population should continue to practice strict COVID-19 precautions post-vaccination, until new strategies for protection are available.

scholarly journals 479. Real-world Evaluation of SARS-CoV-2 Monoclonal Antibodies in Solid Organ Transplant Recipients

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S341-S341
Author(s):  
Kristen Zeitler ◽  
Nicholas Piccicacco ◽  
Lyndsey Bowman ◽  
Jose Montero ◽  
Margarita Cancio ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Organ Transplant ◽  
Panel Member ◽  
Retrospective Chart Review ◽  
Editorial Board Member ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Abstract Background Patients with COVID-19 infection at highest risk for poor outcomes include immunocompromised patients, such as solid organ transplant (SOT) recipients. Monoclonal antibody (mAb) infusions were developed to promote passive immunity. Analysis of the first 200 patients who received SARS-CoV-2 mAb at our hospital showed a 27 % absolute reduction in hospitalization and emergency department (ED) visits. Understanding the role of SARS-CoV-2 mAb therapy in management of the SOT population is likely to inform decision making for these patients. Methods We conducted a retrospective chart review of SOT patients diagnosed with COVID-19 who received mAb therapy between 11/18/20 and 04/26/21. Patients were excluded if they were < 18 years of age or if they weighed < 40 kg. We compared those patients who were hospitalized or visited the ED within 29 days of mAb therapy to those who recovered without further visits to our hospital. Results A total of 50 SOT patients receiving mAb therapy were included in this analysis. Bamlanivimab was given to 33 patients, while 9 patients received bamlanivimab/etesevimab and 8 patients received casirivimab/imdevimab. Twelve (24 %) patients were hospitalized or visited the ED within 29 days of mAb therapy; 38 patients did not. These 2 groups did not significantly differ by age, gender, body mass index, time from SOT, or other risk factors for severe COVID-19 illness per FDA Emergency Use Authorization guidance. Both groups were primarily made up of kidney transplant recipients (66.7 % and 68.4 %, respectively). Significantly more patients in the hospitalization/ED group were receiving antimetabolites as part of their immunosuppression (IS) regimen prior to COVID-19 diagnosis (100 % vs 68.4 %, p = 0.047). Patients in the hospitalization/ED group received mAbs within a median of 6 days (IQR 3.8) of symptom onset compared to 4 days (IQR 4) (p = 0.006). Conclusion SOT recipients were more likely to be hospitalized or visit the ED due to COVID-19 after mAb if they were receiving antimetabolite IS or received mAb later after symptom onset. These data stress the importance of early mAb administration in all SOT patients, particularly in those on antimetabolite therapy. Disclosures Lyndsey Bowman, PharmD, Veloxis Pharmaceuticals (Advisor or Review Panel member, Speaker’s Bureau) Kami Kim, MD, Regeneron Pharmaceuticals Inc. (Scientific Research Study Investigator)Sanford Guide (Other Financial or Material Support, Editorial Board Member)

scholarly journals Safety of Valganciclovir Dosed 450 MG Three Times Weekly for Cytomegalovirus Prophylaxis in Solid Organ Transplant Recipients Requiring Hemodialysis

2021 ◽  
Author(s):  
Danielle Ecabert ◽  
Christine Pham ◽  
Brett J Pierce ◽  
William L Musick ◽  
Duc T Nguyen ◽  
...  
Keyword(s):  
Renal Function ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Severe Neutropenia ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Abstract Background Valganciclovir is the most commonly used antiviral for cytomegalovirus (CMV) prophylaxis in solid organ transplant recipients. However, there are limited clinical outcomes-supported data available to guide valganciclovir dosing in patients on hemodialysis (HD). This study aimed to assess the safety of our institution’s current dosing strategy of valganciclovir 450 mg three times weekly post-HD. Methods This was a single-center retrospective review of all adult non-kidney transplant recipients between May 2016 and June 2018. Patients with end stage renal disease requiring HD for >28 days post-transplant receiving valganciclovir 450 mg three times weekly post-HD were matched with non-HD patients receiving valganciclovir prophylaxis dosed per renal function. The primary endpoints were incidence of leukopenia, neutropenia, and thrombocytopenia while on valganciclovir prophylaxis. Results A total of 465 non-kidney transplants were performed during the study period, with 37 patients included in the HD group who were matched to 111 control patients in the non-HD group. Liver transplant recipients comprised 84% and 72% of each group, with none being CMV D+/R-. The rates of leukopenia (51.4% vs. 51.4%, p = 1.00), severe neutropenia (ANC <500 cells/µL, 15.8% vs. 14.0%, p = 0.85), and thrombocytopenia (24.3% vs. 20.7%, p = 0.64) were similar in both HD and non-HD groups. There were no cases of CMV infection while on valganciclovir prophylaxis in either group. Conclusions Valganciclovir 450 mg three times weekly was found to have similar rates of leukopenia, neutropenia, thrombocytopenia, and CMV infection in comparison to valganciclovir dosed per renal function in non-HD transplant recipients.

Impact of a Clinical Solid Organ Transplant Pharmacist on Tacrolimus Nephrotoxicity, Therapeutic Drug Monitoring, and Institutional Revenue Generation in Adult Kidney Transplant Recipients

2016 ◽  
Vol 26 (4) ◽  
pp. 314-321 ◽  
Author(s):  
Shawn P. Griffin ◽  
Joelle E. Nelson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Kidney Transplant ◽  
Drug Monitoring ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Adult Kidney

Context: Tacrolimus requires close therapeutic drug monitoring (TDM) to ensure efficacy and minimize adverse effects. Pharmacists are uniquely positioned on transplant teams to interpret levels and recommend therapy modifications. Their impact in the immediate postoperative setting has not been described previously. Objective: To evaluate the impact of a clinical solid organ transplant pharmacist on nephrotoxicity, TDM, and revenue generation in adult kidney transplant recipients on tacrolimus. Design, Setting, and Patients: Retrospective assessment of adult kidney transplant recipients at University of Florida Health Shands Hospital. Intervention: A transplant pharmacist rounded 5 days a week and made medication recommendations on transplant recipients—including tacrolimus dose modifications based on levels. Pharmacy services were expanded to include medication reconciliation, medication counseling, and delivery of discharge medications to bedside. Main Outcome Measure: Incidence of nephrotoxicity during tacrolimus exposure. Results: Of the 70 kidney transplant recipients in the postpharmacist cohort, 18 (25.7%) experienced nephrotoxicity while on tacrolimus, compared to 18 (25%) of the 72 in the prepharmacist cohort ( P = .922). A significantly greater proportion of recipients who experienced nephrotoxicity were male, had hypertension, or experienced delayed or slow graft function. The rate of appropriately drawn tacrolimus troughs significantly increased from 23.4% to 30.3% in the postpharmacist cohort ( P < .001). The median outpatient pharmacy revenue generated per recipient significantly increased from US$345.49 (interquartile range [IQR]: 0-4727.56) to US$4834.95 per recipient (IQR: 3592.78-6224.60; P < .001). The length of stay (7 days, IQR: 6-9, vs 8 days, IQR: 6-9; P = .107) and the 30-day readmission rate were similar between groups (20.8% vs 21.4%; P = .931).

Aspergillus Infections among Solid Organ Transplant Recipients: A Case Study

1997 ◽  
Vol 7 (4) ◽  
pp. 187-189
Author(s):  
Joann Pfundstein
Keyword(s):  
Mortality Rate ◽  
Transplant Recipient ◽  
Heart Transplant ◽  
Organ Transplant ◽  
Heart Transplant Recipient ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Solid Organ Transplant Recipients

Infection remains a major cause of morbidity and mortality among transplant recipients. Aspergillus infections in particular are associated with a high mortality rate. The diagnosis of Aspergillus among transplant recipients may be difficult, because many patients have multiple complications. This article presents a case of Aspergillus in a heart transplant recipient. The discussion provides an overview of the presentation, diagnosis, and treatment of Aspergillus infections.

scholarly journals 540. Prolonged Viral Shedding of SARS-CoV-2 In Solid Organ Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S337-S337
Author(s):  
Hannah Nam ◽  
Scott C Roberts ◽  
Sajal D Tanna ◽  
Michael G Ison
Keyword(s):  
Median Duration ◽  
Severe Disease ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Viral Kinetics ◽  
Viral Shedding ◽  
Number Of Patients

Abstract Background Solid organ transplant (SOT) recipients are more susceptible to viral infection and present with differing viral kinetics when compared to non-immunocompromised cohorts. The duration of viral shedding in SOT recipients with SARS-CoV-2 infection is unknown. Methods All SOT recipients with a diagnosed of SARS-CoV-2 by nasopharyngeal of bronchoalveolar lavage RT-qPCR from March 06, 2020 to May 31, 2020 were identified. Viral shedding duration was obtained by evaluating all subsequent SARS-CoV-2 PCR results following initial positivity over time. Severity classification was defined as mild (outpatient), moderate (hospitalized), and severe (ICU level care). Data were obtained from electronic medical record case review and analyzed with Stata 16. Results 71 patients with a positive SARS-CoV-2 PCR test were identified. 50 (70.4%) were classified as mild/moderate disease, while 21 (29.5%) had severe disease. Median age was 56.5 (IQR 45 – 61.3) years, and 56.9% (n = 41) were male. Older age was significantly associated with severe disease. A disproportionate number of patients were African American/Black or Hispanic at 72.2% (n=52). Interestingly, Caucasian race was significantly associated with less severe outcomes (p=0.038). The majority of patients were kidney transplant recipients (46, 63.9%), followed by liver (13, 18.1%), heart (6, 8.3%), lung (3, 4.2%), and pancreas (9, 12.5%) with a median duration from transplantation at 5 (IQR 3 – 17) years. Overall mortality was 5.6% (n=4), with all deaths occurring only in those with severe disease (19.1%, n=4). Prolonged viral shedding was observed in few patients, with median duration of SARS-CoV-2 PCR positivity at 32 (IQR 18.5 – 41.0) days. One kidney recipient was observed with up to 64 days of positive SARS-CoV-2 RT-PCR from initial diagnosis despite not developing severe disease. Demographics and Outcomes Duration of Viral Shedding in SOT Patients with COVID-19 Conclusion COVID-19 can lead to significant outcomes in SOT with increased mortality in those with severe disease, as well as prolonged viral shedding. Further studies are needed to elucidate the full duration of viral shedding in this population. Disclosures Michael G. Ison, MD MS, AlloVir (Consultant)

scholarly journals Heart transplant recipient survivor from COVID-19: The first case of Turkey

2020 ◽  
Vol 28 (4) ◽  
pp. 674-679
Author(s):  
Güle Çınar
Keyword(s):  
Transplant Recipient ◽  
Heart Transplant ◽  
Organ Transplant ◽  
Heart Transplant Recipient ◽  
Solid Organ Transplant ◽  
Primary Concern ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Any highly infectious and rapidly spreading disease is a primary concern for immunocompromised solid organ transplant recipients. The number of data about the spectrum of clinical illness, the treatment modalities, and the outcomes of COVID-19 in this vulnerable population is scant and still remains empirical. Herein, we report the first COVID-19 case of a heart transplant recipient in Turkey who presented with fever, postnasal discharge, and myalgias for two days. The possibility of lung involvement was ruled out by thoracic computed tomography. Despite stable vital signs, we reduced the intensity of immunosuppressive therapy and maintained home self-isolation promptly. We also commenced a five-day course of hydroxychloroquine 200 mg q12h initially. After confirmation of real-time reverse-transcriptase-polymerase-chain-reaction testing of the nasopharyngeal swab positive for COVID-19, the patient was hospitalized. After a loading dose of favipiravir 1,600 mg b.i.d., the patient received a five-day course of favipiravir 600 mg q12h. He was discharged with cure after 23 days of hospital isolation and treatment. In conclusion, treatment process can be affected by the daily electrocardiography, hand-held portable echocardiography, myocardial injury markers, and pulse oximeter for self-monitoring in the follow-up of previous heart transplant recipients suffering from COVID-19. The lack of treatment protocols in the solid organ transplant recipients with COVID-19 infection and the controversies about the protective effect of immunosuppression invite a global and update discussion.

Cryptococcosis

2020 ◽  
pp. 1359-1361
Author(s):  
William G. Powderly ◽  
J. William Campbell ◽  
Larry J. Shapiro
Keyword(s):  
Initial Period ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Suppressive Therapy ◽  
Cell Mediated Immunity ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Transplant Recipients ◽  
Common Presentation ◽  
Solid Organ Transplant Recipients

Cryptococcus neoformans, which is found worldwide as a soil organism and thought to be transmitted by inhalation, most often causes disease in patients with abnormal cell-mediated immunity, notably patients with HIV infection and solid-organ transplant recipients, but the infection also occurs rarely in apparently immunocompetent people in restricted geographical areas, especially involving C. neoformans var. gattii. The most common presentation is with subacute meningoencephalitis, but other manifestations (e.g. isolated pulmonary disease or disseminated infection, are well described). Diagnosis is usually by culture or serology. Untreated cryptococcal meningitis is fatal: aside from supportive care (including monitoring for raised intracranial pressure), the therapy of choice is an initial period (at least two weeks) of amphotericin B (ideally with flucytosine), followed by at least 3 months of fluconazole. Most immunocompromised patients subsequently require maintenance suppressive therapy, usually with fluconazole.

scholarly journals Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients

2020 ◽  
Vol 8 (1) ◽  
pp. e000908 ◽  
Author(s):  
Megan H Trager ◽  
Shana M Coley ◽  
Geoffrey Dube ◽  
Shaheer Khan ◽  
Matthew Ingham ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Solid Organ ◽  
Combination Immunotherapy ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Solid Organ Transplant Recipients

BackgroundImmune checkpoint blockade has emerged as a highly effective treatment for patients with metastatic melanoma and cutaneous squamous cell carcinoma. Nivolumab blocks the interactions between programmed cell death protein 1 and programmed death ligand 1 allowing for activation of a latent immune response against the malignancy. Ipilimumab binds to and blocks cytotoxic T-lymphocyte-associated protein 4, alleviating the negative regulation of T-cell activation that is mediated by that checkpoint. Combination therapy with nivolumab and ipilimumab is associated with longer overall survival at 5 years compared with nivolumab monotherapy. Solid organ transplant recipients have a significantly higher risk of malignancies compared with the general population. There is limited data surrounding the efficacy of combination immunotherapy in solid organ transplant recipients, as these patients were excluded from seminal trials due to risk of organ rejection.Case presentationsHere we present four cases of combination immunotherapy in kidney transplant recipients. Three patients had metastatic melanoma, and one patient had metastatic cutaneous squamous cell carcinoma. Two patients had radiographic responses from immunotherapy, one patient had stable disease, and one patient had disease progression. Only one patient had biopsy-proven rejection. At last follow-up, three patients had functioning grafts, though one required hemodialysis after treatment, and one patient succumbed to disease, but graft function remained intact throughout her course.ConclusionsThese cases describe the use of ipilimumab and nivolumab combination immunotherapy for cutaneous malignancies in kidney transplant recipients. They highlight the potential to preserve kidney graft function while effectively treating the disease.Trial Registration numberNCT03816332.

scholarly journals Cell-Mediated and Humoral Immune Response to 2-Dose SARS-CoV2 mRNA vaccination in Immunocompromised patient population

2021 ◽  
Author(s):  
Muthukumar Ramanathan ◽  
Kanagavel Murugesan ◽  
Lu M Yang ◽  
Cristina Costales ◽  
Philip L Bulterys ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Transplant Recipients ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Solid Organ Transplant Recipients

Characterization of cell-mediated and humoral immune responses to SARS-CoV2 mRNA vaccine has implications for protective immunity in immunocompromised patients. However, studies have demonstrated poor humoral response to SARS-CoV2 mRNA vaccine in immunocompromised patients and data on cellular immune response are currently lacking. Here we compared immune response after 2-dose vaccination in 100 immunocompromised patients (solid organ transplant recipients, hematologic malignancy, autoimmune condition, and primary immunodeficiency) and 16 immunocompetent healthy healthcare workers. We find that 100% (CI=80.6-100%) of immunocompetent individuals show positive cell-mediated and humoral immune response post vaccination while only 50% (CI=40.4-59.6%) of immunocompromised patients show humoral immune response and 69% (CI=59.4-77.2%) have a positive cell-mediated immune response. 21% of immunocompromised patients have no humoral immune response or cell-mediated immune response and thus are likely vulnerable to SARS-CoV2 infection. Monitoring of immune response in immunocompromised populations, particularly in high-risk immunocompromised patients (solid organ transplant recipients, patients with severe autoimmunity, and those ≥50 years), with clinical IGRA and serological assay after vaccination may identify patients who may benefit from revaccination or prophylactic monoclonal antibody therapy to prevent COVID-19 in this patient population

scholarly journals COVID-19 Severity and Mortality in Solid Organ Transplantation: Differences between Liver, Heart, and Kidney Recipients

2021 ◽  
Vol 2 (3) ◽  
pp. 296-303 ◽  
Author(s):  
Ricardo Wesley Alberca ◽  
Gabriela Gama Freire Alberca ◽  
Lucas Chaves Netto ◽  
Raquel Leão Orfali ◽  
Sarah Cristina Gozzi-Silva ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Kidney Transplant ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Control Group ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Solid Organ Transplant Recipients ◽  
Liver Transplant Recipients

The infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can generate a wide spectrum of clinical manifestations ranging from asymptomatic to severe respiratory and systemic disease with coagulation disorder named coronavirus disease 2019 (COVID-19). Patients with comorbidities have been identified as risk groups for severe COVID-19, also having a higher death risk. Previous reports have conflicting results regarding if solid organ transplant recipients present an increased risk for COVID-19. Nevertheless, previous investigations failed to distinguish between different organs received or made a longitudinal investigation on those patients. We recruited 39 solid organ transplant recipients: 25 kidney transplant recipients, 7 heart transplant recipients, and 7 liver transplant recipients and 25 age-matched non-transplant COVID-19 patients without comorbidities (control group) and compared daily laboratory data in addition to performing survival analysis. Heart and kidney transplant recipients presented an increase in several COVID-19 severity-associated biomarkers, such as neutrophil-to-lymphocyte ratio and thrombocytopenia, in comparison to the control group and liver transplant recipients. Heart and kidney transplant recipients also presented an increase in the need for intensive care and invasive mechanical ventilation during the disease’s course. Importantly, heart and kidney transplant recipients presented a higher mortality rate in comparison to liver transplant recipients and non-transplant recipients. In our cohort, heart and kidney transplant recipients presented a difference in clinical characteristics and survival rate in comparison to liver transplant recipients. Further investigation involving immune response to SARS-CoV-2 in solid organ recipients should consider and separate patients according to the organ grafted.

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