Background: Remdesivir (RDV) has been shown to reduce hospitalization and mortality in COVID-19 patients. Resistance mutations caused by RDV are rare and have been predominantly reported in patients who are on prolonged therapy and immunocompromised. We investigate the effects of RDV treatment on intra-host SARS-CoV-2 diversity and low-frequency mutations in moderately ill hospitalized COVID-19 patients and compare them to patients without RDV treatment.
Methods: From March 2020 to April 2022, sequential collections of nasopharyngeal and mid-turbinate swabs were obtained from 14 patients with and 30 patients without RDV treatment. Demographic and clinical data on all patients were reviewed. A total of 109 samples were sequenced and mutation analyses were performed.
Results: Previously reported drug resistant mutations in nsp12 were not identified during short courses of RDV therapy. In genes encoding and surrounding the replication complex (nsp6-nsp14), low-frequency minority variants were detected in 7/14 (50%) and 18/30 (60%) patients with and without RDV treatment, respectively. We did not detect significant differences in within-host diversity and positive selection between the RDV-treated and untreated groups.
Conclusions: Minimal intra-host variability and stochastic low-frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. The barrier to RDV resistance is high in patients with moderate disease. Patients undergoing short regimens of RDV therapy should continue to be monitored.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10522481 | PMC |
| http://dx.doi.org/10.1111/irv.13179 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022.
Clin Trials
January 2025
Rare Diseases Team, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Background/aims: Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.
View Article and Find Full Text PDFIn the context of Chinese clinical texts, this paper aims to propose a deep learning algorithm based on Bidirectional Encoder Representation from Transformers (BERT) to identify privacy information and to verify the feasibility of our method for privacy protection in the Chinese clinical context. We collected and double-annotated 33,017 discharge summaries from 151 medical institutions on a municipal regional health information platform, developed a BERT-based Bidirectional Long Short-Term Memory Model (BiLSTM) and Conditional Random Field (CRF) model, and tested the performance of privacy identification on the dataset. To explore the performance of different substructures of the neural network, we created five additional baseline models and evaluated the impact of different models on performance.
View Article and Find Full Text PDFElevated serum vitamin B12 concentrations in a patient with pancreatic exocrine insufficiency.
Biomark Med
January 2025
The Nutristasis Unit, Synnovis, St. Thomas' Hospital, London, UK.
This case describes a patient with pancreatic exocrine insufficiency and persistently elevated serum vitamin B12 concentrations that were not due to supplementation or associated with hepatic or hematological pathology. Laboratory investigations suggested the presence of macro-B12 as the cause of this patient's raised serum vitamin B12. Macro-B12 is often formed when vitamin B12-vitamin binding proteins (transcobalamin and haptocorrin) complex with immunoglobulins.
View Article and Find Full Text PDFAdaptive promising zone design for sequential parallel comparison design with continuous outcomes.
Clin Trials
January 2025
Department of Biostatistics, University of Florida, Gainesville, FL, USA.
Introduction: The sequential parallel comparison design has emerged as a valuable tool in clinical trials with high placebo response rates. To further enhance its efficiency and effectiveness, adaptive strategies, such as sample size adjustment and allocation ratio modification can be employed.
Methods: We compared the performance of Jennison and Turnbull's method and the Promising Zone approach for sample size adjustment in a two-phase sequential parallel comparison design study.
Bilateral Choroidal Metastases from Primary Cutaneous Melanoma Following Nivolumab Discontinuation: A Case Report.
Ocul Immunol Inflamm
January 2025
Ocular Oncology Service, Institute of Oncology, Tecnologico de Monterrey, Monterrey, Mexico.
Purpose: To present the case of a young patient with BRAF V600E-mutant cutaneous melanoma who developed bilateral choroidal metastases complicated by neovascular glaucoma (NVG) in both eyes following the interruption of nivolumab therapy.
Methods: A 28-year-old female with primary cutaneous melanoma of the left hand underwent surgical resection and adjuvant nivolumab. Immunotherapy was discontinued due to immune-related acute interstitial nephritis.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!