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Host-pathogen dynamics in longitudinal clinical specimens from patients with COVID-19.
Lin, Michelle J; Rachleff, Victoria M; Xie, Hong; Shrestha, Lasata; Lieberman, Nicole A P; Peddu, Vikas; Addetia, Amin; Casto, Amanda M; Breit, Nathan; Mathias, Patrick C; Huang, Meei-Li; Jerome, Keith R; Greninger, Alexander L; Roychoudhury, Pavitra.
Afiliación
  • Lin MJ; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Rachleff VM; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Xie H; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Shrestha L; Program in Molecular and Cellular Biology, University of Washington School of Medicine, Seattle, WA, USA.
  • Lieberman NAP; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Peddu V; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Addetia A; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Casto AM; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Breit N; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Mathias PC; Division of Allergy and Infectious Diseases, University of Washington School of Medicine, Seattle, WA, USA.
  • Huang ML; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Jerome KR; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Greninger AL; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, 98102, USA.
  • Roychoudhury P; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Sci Rep ; 12(1): 5856, 2022 04 07.
Article en En | MEDLINE | ID: mdl-35393464
Rapid dissemination of SARS-CoV-2 sequencing data to public repositories has enabled widespread study of viral genomes, but studies of longitudinal specimens from infected persons are relatively limited. Analysis of longitudinal specimens enables understanding of how host immune pressures drive viral evolution in vivo. Here we performed sequencing of 49 longitudinal SARS-CoV-2-positive samples from 20 patients in Washington State collected between March and September of 2020. Viral loads declined over time with an average increase in RT-QPCR cycle threshold of 0.87 per day. We found that there was negligible change in SARS-CoV-2 consensus sequences over time, but identified a number of nonsynonymous variants at low frequencies across the genome. We observed enrichment for a relatively small number of these variants, all of which are now seen in consensus genomes across the globe at low prevalence. In one patient, we saw rapid emergence of various low-level deletion variants at the N-terminal domain of the spike glycoprotein, some of which have previously been shown to be associated with reduced neutralization potency from sera. In a subset of samples that were sequenced using metagenomic methods, differential gene expression analysis showed a downregulation of cytoskeletal genes that was consistent with a loss of ciliated epithelium during infection and recovery. We also identified co-occurrence of bacterial species in samples from multiple hospitalized individuals. These results demonstrate that the intrahost genetic composition of SARS-CoV-2 is dynamic during the course of COVID-19, and highlight the need for continued surveillance and deep sequencing of minor variants.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido