A program for real-time surveillance of SARS-CoV-2 genetics

Area of Science:

• Genomic surveillance
• Virology
• Public health infrastructure

Background:

• The COVID-19 pandemic highlighted the critical need for rapid genomic surveillance of SARS-CoV-2 variants.
• Existing infrastructure was insufficient for timely detection and monitoring of emerging viral lineages.
• A robust system was required for sample processing, sequencing, and data dissemination to public health authorities.

Purpose of the Study:

• To describe the development and deployment of a nationwide infrastructure for SARS-CoV-2 genomic surveillance in the United States.
• To detail the 'Virseq' protocol for high-coverage, mutation-resistant whole-genome sequencing.
• To establish a model for rapid response to emerging infectious disease threats.

Main Methods:

• Development of a modular infrastructure for sample sequestration, consolidation, and characterization.
• Implementation of the 'Virseq' protocol for whole-genome sequencing of SARS-CoV-2 isolates.
• Analysis of 594,832 SARS-CoV-2 genomes and characterization of 379 co-infections.

Main Results:

• Successfully sequenced 594,832 high-coverage SARS-CoV-2 genomes from March 2020 to July 2023.
• The 'Virseq' protocol demonstrated mutation resistance and captured all major SARS-CoV-2 lineages.
• Identified and characterized 379 clinically relevant multi-strain co-infections.
• Developed simulation methods for robust detection of emerging lineages.

Conclusions:

• The developed infrastructure effectively supports national genomic surveillance programs, including the U.S. Centers for Disease Control and Prevention's efforts.
• The described system provides a scalable model for national-level rapid response to emerging pandemics.
• Continuous genomic surveillance is essential for monitoring viral evolution and informing public health strategies.