Genomic analysis of the early COVID-19 pandemic in Haiti reveals Caribbean-specific variant dynamics.

Pathogen sequencing during the COVID-19 pandemic has generated more whole genome sequencing data than for any other epidemic, allowing epidemiologists to monitor the transmission and evolution of SARS-CoV-2. However, large parts of the world are heavily underrepresented in sequencing efforts, including the Caribbean islands. We performed genome sequencing of SARS-CoV-2 from upper respiratory tract samples collected in Haiti during the spring of 2020.

Microbial Type IA Topoisomerase C-Terminal Domain Sequence Motifs, Distribution and Combination.

Type IA topoisomerases have highly conserved catalytic N-terminal domains for the cleaving and rejoining of a single DNA/RNA strand that have been extensively characterized. In contrast, the C-terminal region has been less covered. Two major types of small tandem C-terminal domains, Topo_C_ZnRpt (containing C4 zinc finger) and Topo_C_Rpt (without cysteines) were initially identified in and topoisomerase I, respectively.

A Yeast-Based Screening System for Differential Identification of Poisons and Suppressors of Human Topoisomerase I.

Background: Inhibition of human topoisomerase I (TOP1) by camptothecin and topotecan has been shown to reduce excessive transcription of PAMP (Pathogen-Associated Molecular Pattern)-induced genes in prior studies, preventing death from sepsis in animal models of bacterial and SARS-CoV-2 infections. The TOP1 catalytic activity likely resolves the topological constraints on DNA that encodes these genes to facilitate the transcription induction that leads to excess inflammation. The increased accumulation of TOP1-DNA covalent complex (TOP1cc) following DNA cleavage is the basis for the anticancer efficacy of the TOP1 poisons developed for anticancer treatment.

Yearlong COVID-19 Infection Reveals Within-Host Evolution of SARS-CoV-2 in a Patient With B-Cell Depletion.

B-cell-depleting therapies may lead to prolonged disease and viral shedding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this viral persistence raises concern for viral evolution. We report sequencing of early and late samples from a 335-day infection in an immunocompromised patient. The virus accumulated a unique deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient.

Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion.

Background: B-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution.

Methods: Amplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs.