Reconstruction of SARS-CoV-2 transmissibility within households in the UK Virus Watch Study

Abstract Background Households provide an ideal setting to study SARS-CoV-2 transmission modes due to the close proximity and extended exposure among members. Understanding the patterns of who infects whom during infectious disease outbreaks is crucial for implementing effective control measures globally. Combining genomic data with epidemiological insights can help clarify and infer pathways of viral spread. Methods We analyse SARS-CoV-2 whole genome sequences from 237 subjects across 162 households recruited to the Virus Watch Prospective Community Cohort Study ( n = 372 total participants). We consider minority variants as an indicator of within-host genomic diversity and incorporate these into a phylogenetic model to reconstruct the relationships between genomes, leading to a more accurate reconstruction of transmission than if only the consensus variation were used. Results Here we show that of the 73 households with multiple infected participants, both consensus and within-host phylogenetic analyses identify eight households in which one or more secondary cases appear to arise from separate community introductions rather than within-household transmission. These households are excluded from the bottleneck and within-host transmission analyses. For the remaining 65 households, including minority variants when reconstructing phylogeny allows us to infer transmission chains that are otherwise uncertain with consensus variants only. Conclusions Integrating within-host genetic diversity into a phylogenetic model alongside epidemiological data provides a robust approach to accurately identify true household transmission events, assess risk factors for infection acquisition and spread, and improve the estimation of the secondary attack rate