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Remdesivir Resistance in Transplant Recipients With Persistent Coronavirus Disease 2019.

ABSTRACT: New mutations conferring resistance to SARS-CoV-2 therapeutics have important clinical implications. We describe the first cases of an independently acquired V792I RNA-dependent RNA polymerase mutation developing in renal transplant recipients after remdesivir exposure. Our work underscores the need for augmented efforts to identify concerning mutations and address their clinical implications.

SUBMITTER: Hogan JI

PROVIDER: S-EPMC9619446 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Remdesivir Resistance in Transplant Recipients With Persistent Coronavirus Disease 2019.

Hogan John I JI Duerr Ralf R Dimartino Dacia D Marier Christian C Hochman Sarah E SE Mehta Sapna S Wang Guiqing G Heguy Adriana A

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20230101 2

New mutations conferring resistance to SARS-CoV-2 therapeutics have important clinical implications. We describe the first cases of an independently acquired V792I RNA-dependent RNA polymerase mutation developing in renal transplant recipients after remdesivir exposure. Our work underscores the need for augmented efforts to identify concerning mutations and address their clinical implications. ...[more]

PMID: 36156117

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Remdesivir resistance in transplant recipients with persistent COVID-19.

Project description:The medical community currently lacks robust data regarding the incidence, prevalence, and clinical significance of mutations associated with resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) therapeutics. This report describes two renal transplant recipients who, after remdesivir exposure, developed a de novo V792I RNA-dependent RNA polymerase (RdRp) mutation that has recently been found to confer resistance to remdesivir in vitro . To the best of our knowledge, this publication is the first to document the emergence of V792I in patients treated with remdesivir. Our work underscores the critical need for augmented efforts to identify concerning mutations and address their clinical implications.

| S-EPMC9258299 | biostudies-literature

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

Project description:IntroductionRemdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients.MethodsWe present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed.ResultsMean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug.ConclusionIn our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.

| S-EPMC8257403 | biostudies-literature

Remdesivir in solid organ transplant recipients with COVID-19: a systematic review and meta-analysis.

Project description:BackgroundThe use of remdesivir in solid organ transplant recipients (SOTRs) with coronavirus disease 2019 (COVID-19) has been studied. The present systematic review and analysis aimed to assess its effectiveness in this population.MethodsA comprehensive search of PubMed, Cochrane Library, Web of Science, Embase, medRxiv, and Google Scholar was conducted to identify relevant articles published up to April 2024. The quality of the included studies was evaluated using the Cochrane assessment tool. Data analysis was performed using the Comprehensive Meta-Analysis software ver. 3.0.ResultsThe meta-analysis included seven eligible retrospective studies, involving a total of 574 SOTRs. The findings indicated no significant differences in mortality rate (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.59-2.39), hospitalization rate (OR, 0.69; 95% CI, 0.10-4.79), need for mechanical ventilation (OR, 0.98; 95% CI, 0.44-2.18), or need for oxygen therapy (OR, 3.73; 95% CI, 0.75-18.34) between the groups that received remdesivir and those that did not. However, a statistically significant difference was observed in the rate of intensive care unit admissions between the two groups (OR, 2.39; 95% CI, 1.24-4.57).ConclusionsOur meta-analysis found that remdesivir offers no clinical benefits to SOTRs infected with COVID-19. Additional high-quality research is required to assess the potential clinical advantages of remdesivir for SOTRs with COVID-19.

| S-EPMC11464156 | biostudies-literature

COVID-19 in kidney transplant recipients.

Project description: Not available

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COVID-19 in lung transplant recipients.

Project description:Solid organ transplant recipients are considered at high risk for COVID-19 infection due to chronic immune suppression; little data currently exists on the manifestations and outcomes of COVID-19 infection in lung transplant recipients. Here we report 8 cases of COVID-19 identified in patients with a history of lung transplant. We describe the clinical course of disease as well as preexisting characteristics of these patients.

| S-EPMC7300568 | biostudies-literature

COVID-19 infection in kidney transplant recipients.

Project description:By 21 March 2020 infections related to the novel coronavirus SARS-CoV-2 had affected people from 177 countries and caused 11,252 reported deaths worldwide. Little is known about risk, presentation and outcomes of SARS-CoV-2 (COVID-19) infection in kidney transplantation recipients, who may be at high-risk due to long-term immunosuppression, comorbidity and residual chronic kidney disease. Whilst COVID-19 is predominantly a respiratory disease, in severe cases it can cause kidney and multi-organ failure. It is unknown if immunocompromised hosts are at higher risk of more severe systemic disease. Therefore, we report on seven cases of COVID-19 in kidney transplant recipients (median age 54 (range 45-69), three females, from a cohort of 2082 managed transplant follow-up patients) over a six-week period in three south London hospitals. Two of seven patients presented within three months of transplantation. Overall, two were managed on an out-patient basis, but the remaining five required hospital admission, four in intensive care units. All patients displayed respiratory symptoms and fever. Other common clinical features included hypoxia, chest crepitation, lymphopenia and high C-reactive protein. Very high D dimer, ferritin and troponin levels occurred in severe cases and likely prognostic. Immunosuppression was modified in six of seven patients. Three patients with severe disease were diabetic. During a three week follow up one patient recovered, and one patient died. Thus, our findings suggest COVID-19 infection in kidney transplant patients may be severe, requiring intensive care admission. The symptoms are predominantly respiratory and associated with fever. Most patients had their immunosuppression reduced and were treated with supportive therapy.

| S-EPMC7142878 | biostudies-literature

COVID-19 vaccination in kidney transplant recipients.

Project description: Not available

| S-EPMC8475856 | biostudies-literature

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19

Project description:Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals. GRAPHICAL ABSTRACT

| S-EPMC9343962 | biostudies-literature

Analyzing COVID-19 Vaccine Responses in Transplant Recipients.

Project description:COVID-19 vaccination has significantly impacted the global pandemic by reducing the severity of infection, lowering rates of hospitalization, and reducing morbidity/mortality in healthy individuals. However, the degree of vaccine-induced protection afforded to renal transplant recipients who receive forms of maintenance immunosuppression remains poorly defined. This is particularly important when we factor in the emergence of SARS-CoV-2 variants of concern (VOCs) that have defined mutations that reduce the effectiveness of Ab responses targeting the Spike Ags from the ancestral Wuhan-Hu-1 variants employed in the most widely used vaccine formats. In this study, we describe a qualitative, longitudinal analysis of neutralizing Ab responses against multiple SARS-CoV-2 VOCs in 129 renal transplant recipients who have received three doses of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Our results reveal a qualitative and quantitative reduction in the vaccine-induced serological response in transplant recipients versus healthy controls where only 51.9% (67 of 129) made a measurable vaccine-induced IgG response and 41.1% (53 of 129) exhibited a significant neutralizing Ab titer (based on a pseudovirus neutralization test value >50%). Analysis on the VOCs revealed strongest binding toward the wild-type Wuhan-Hu-1 and Delta variants but none with both of the Omicron variants tested (BA1 and BA2). Moreover, older transplant recipients and those who are on mycophenolic acid as part of their maintenance therapy exhibited a profound reduction in all of the analyzed vaccine-induced immune correlates. These data have important implications for how we monitor and manage transplant patients in the future as COVID-19 becomes endemic in our populations.

| S-EPMC10615654 | biostudies-literature

COVID-19 in transplant recipients: The Spanish experience.

Project description:We report the nationwide experience with solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients diagnosed with coronavirus disease 2019 (COVID-19) in Spain until 13 July 2020. We compiled information for 778 (423 kidney, 113 HSCT, 110 liver, 69 heart, 54 lung, 8 pancreas, 1 multivisceral) recipients. Median age at diagnosis was 61 years (interquartile range [IQR]: 52-70), and 66% were male. The incidence of COVID-19 in SOT recipients was two-fold higher compared to the Spanish general population. The median interval from transplantation was 59 months (IQR: 18-131). Infection was hospital-acquired in 13% of cases. No donor-derived COVID-19 was suspected. Most patients (89%) were admitted to the hospital. Therapies included hydroxychloroquine (84%), azithromycin (53%), protease inhibitors (37%), and interferon-β (5%), whereas immunomodulation was based on corticosteroids (41%) and tocilizumab (21%). Adjustment of immunosuppression was performed in 85% of patients. At the time of analysis, complete follow-up was available from 652 patients. Acute respiratory distress syndrome occurred in 35% of patients. Ultimately, 174 (27%) patients died. In univariate analysis, risk factors for death were lung transplantation (odds ratio [OR]: 2.5; 95% CI: 1.4-4.6), age >60 years (OR: 3.7; 95% CI: 2.5-5.5), and hospital-acquired COVID-19 (OR: 3.0; 95% CI: 1.9-4.9).

| S-EPMC9906239 | biostudies-literature

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