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

The COVID-19 pandemic brought forth an urgent need for widespread genomic surveillance for rapid detection and monitoring of emerging SARS-CoV-2 variants. It necessitated design, development, and deployment of a nationwide infrastructure designed for sequestration, consolidation, and characterization of patient samples that disseminates de-identified information to public authorities in tight turnaround times. Here, we describe our development of such an infrastructure, which sequenced 594,832 high coverage SARS-CoV-2 genomes from isolates we collected in the U.S. from March 13th 2020 to July 3rd 2023. Our sequencing protocol (‘Virseq’) generates mutation-resistant sequencing of the entire SARS-CoV-2 genome, capturing all major lineages. We also characterize 379 clinically relevant SARS-CoV-2 multi-strain co-infections and ensure robust detection of emerging lineages via simulation. The modular infrastructure, sequencing, and analysis capabilities we describe support the U.S. Centers for Disease Control national surveillance program and serve as a model for rapid response to emerging pandemics at a national scale. ### Competing Interest Statement All authors (except O.C.) are employees of Labcorp, a provider of clinical diagnostic services. O.C. is a former Labcorp employee and is now employed by Fortrea, Inc. ### Funding Statement No grants or financial support were used for this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Western Institutional Review Board waived ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Figures S1-13 and Table S1 may be found in the Supplementary Materials . A list of de-identified LCIDs and their corresponding GISAID EPI_ISL IDs from samples analyzed in this study that were reported to CDC may be found in the Supplementary Data . A list of LCIDs used to construct the empirical simulation model are included in the Supplementary Data . Additionally, all processed data used to generate [Figures 2b][1], 3b , 4-6 , and S1-13 are provided in the Supplementary Data . Data used to generate [Figure 3a][2] are provided in Table S1 . [1]: #F2 [2]: #F3