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Brenda Martínez-González1,2, María Eugenia Soria1,2, Ana Isabel de Ávila1

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The complexity of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) mutant spectra decreased over time during the COVID-19 pandemic. This reduction in viral genome heterogeneity was not due to viral replication changes but likely epidemiological factors.

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Area of Science:

  • Virology
  • Genetics
  • Epidemiology

Background:

  • RNA viruses, including SARS-CoV-2, exhibit quasispecies dynamics, characterized by complex and dynamic mutant spectra.
  • SARS-CoV-2 demonstrates significant intrahost genetic and functional heterogeneity, contributing to its rapid evolution.
  • Understanding viral evolution and heterogeneity is crucial for managing pandemics.

Purpose of the Study:

  • To investigate changes in the mutant spectrum complexity of SARS-CoV-2 isolates over time.
  • To determine if observed changes in heterogeneity were linked to viral replication accuracy or other factors.
  • To explore the implications of evolving viral traits during a pandemic.

Main Methods:

  • Analysis of SARS-CoV-2 isolates collected in Madrid, Spain, from 2020 to 2022.
  • Comparison of mutant spectrum complexity (intrahost viral genome heterogeneity) between early and late COVID-19 waves.
  • Replication of viral isolates and biological clones in Vero E6 cells to assess heterogeneity development.
  • Sequencing and analysis of viral genomes to track consensus sequence divergence.

Main Results:

  • A significant reduction in mutant spectrum complexity was observed in later COVID-19 waves compared to earlier ones.
  • The consensus sequence of SARS-CoV-2 isolates showed continuous divergence from the initial Wuhan-Hu-1 strain.
  • Mutant spectrum complexity in cell culture was similar for isolates from different waves, indicating the reduction was not due to replicative machinery changes.
  • The findings suggest epidemiological or pathogenetic factors influenced the observed decrease in viral heterogeneity.

Conclusions:

  • The mutant spectrum complexity of SARS-CoV-2 isolates has evolved during the pandemic.
  • The reduction in heterogeneity is likely driven by epidemiological dynamics rather than increased viral replication fidelity.
  • Viral mutant spectrum complexity can be an epidemiologically evolvable trait with implications for pandemic management.