Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n=15). All patients received remdesivir and some also received nirmatrelvir-ritonavir or monoclonal antibodies. Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient treated with remdesivir and nirmatrelvir-ritonavir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n = 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir (n = 3) or therapeutic monoclonal antibodies (n = 4). Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient sequentially treated with nirmatrelvir-ritonavir and remdesivir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

Draft genome sequence of Streptomyces sp. strain ICN988, isolated from Gorgonia sp.

This study elucidates the draft genomic sequence of Streptomyces sp. strain ICN988, an actinomycete isolated from Gorgonia. The assembled genome consists of 6,122,654 bp with a GC content of 73%. A comprehensive analysis revealed 19 biosynthetic gene clusters.

Draft Genome Sequence of Streptomyces sp. Strain ICN903, Isolated from a Seaweed.

Here, we report the whole-genome sequence of the actinomycete Streptomyces sp. strain ICN903, which was isolated from seaweed of the genus Botryocladia. The whole-genome assembly contained 6,122,654 bp with 73% GC content. In total, 19 biosynthetic gene clusters (BGCs), including polyketides and terpenes, were predicted within the sequenced genome.

The Community Health Systems Reform Cycle: Strengthening the Integration of Community Health Worker Programs Through an Institutional Reform Perspective.

To develop guidance for governments and partners seeking to scale community health worker programs, we developed a conceptual framework, collected observations from the scale-up efforts of 7 countries, workshopped the framework with technical groups and with country stakeholders, and reviewed literature in the areas of health and policy reform, change management, institutional development, health systems, and advocacy. We observed that successful scale-up is a complex process of institutional reform. Successful scale-up: (1) depends on a carefully choreographed, problem-driven political process; (2) requires that scaled program models are drawn from solutions that are available in a given health system context and aligned with the resources, capabilities, and commitments of key health sector stakeholders; and (3) emerges from iterative cycles of learning and improvement, rather than a single, linear scale-up effort. We identify stages of the reform process associated with each of these 3 findings: problem prioritization, coalition building, solution gathering, design, program readiness, launch, governance, and management and learning. The resulting Community Health Systems Reform Cycle can be used by government, donors, and nongovernmental partners to prioritize and design community health worker scale-up efforts, diagnose challenges or gaps in successful scale-up and integration, and coordinate the contributions of diverse stakeholders.