Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. The location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.

ALG reports contract testing from Abbott, Cepheid, Novavax, Pfizer, Janssen and Hologic, research support from Gilead, and salary and stock grants for LabCorp an immediate family member, outside of the described work. All other authors declare no competing interests.

This work is supported by NIH NIGMS (R35 GM119774 to T.B.) and the CDC (CDC-RFA-CK22-2204, Pathogens Genomics Centers of Excellence, contract NU50CK000630). Sequencing of specimens by the Brotman Baty Institute of Precision Medicine was funded by Gates Ventures (Seattle Flu Study award), Howard Hughes Medical Institute (HHMI COVID-19 Collaboration Initiative award) and the CDC (contract number 200-2021-10982). Sequencing of specimens by UW Virology was funded by Fast Grants (award 2244), the CDC (contracts 75D30121C10540 and 75D30122C13720) and WA DOH (contract HED26002). Some of the analyses were completed using Fred Hutch Scientific Computing resources (NIH grants S10-OD-020069 and S10-OD-028685). TB is a Howard Hughes Medical Institute Investigator.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Washington State and University of Washington Institutional Review Boards determined this project to be surveillance activity and exempt from review; the need for informed consent was waived through this determination. Under Washington State IRB Exempt Determination 2020-102, symptom onset date, age group, residence county, residence postal code and vaccination history was provided by the Washington Department of Health from the Washington Disease Reporting System for individuals with linked sequenced SARS-CoV-2 samples from March 1, 2021 through December 31, 2022. Sequencing and analysis of samples from the Seattle Flu Study was approved by the Institutional Review Board (IRB) at the University of Washington (protocol STUDY00006181). Sequencing of remnant clinical specimens at UW Virology Lab was approved by the University of Washington Institutional Review Board (protocol STUDY00000408).

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.

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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).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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GISAID and are publicly available with standard metadata (generally consisting of date of sample collection and sometimes county of sample collection). More detailed metadata curated by Washington State Department of Health (WA DOH) of county, postal code, age group and vaccination status were shared with the Fred Hutchinson Cancer Center under a Data Sharing Agreement for Confidential Data with an associated IRB. These more detailed metadata are not currently shared publicly while we seek clearance with WA DOH. GISAID accessions and a sequence-level acknowledgements table are provided in the GitHub repository associated with this manuscript (https://github.com/blab/phylo-kernel-public).

https://github.com/blab/phylo-kernel-public