Speaker
Description
A high proportion of SARS-CoV-2 transmissions happen within households, making accurate identification of sources and recipients of infection within households important for designing effective public health strategies. However, traditional epidemiological data can rarely confirm transmission paths and directions. We used the UK’s Office for National Statistics COVID-19 Infection Survey (CIS) to pinpoint high confidence source-recipient transmission pairs from initial positive tests. We then analysed deep-sequencing data to identify genomic characteristics of those sources and recipient. Finally, we applied these characteristics to a much larger number of potential household transmissions who first tested positive on the same day to determine likely sources and recipients.
The CIS recruited >225,000 UK households between April 2020 and March 2023. Participants aged two and above provided 4 weekly nose and throat swabs initially, and monthly thereafter. Samples underwent RT-PCR testing for SARS-CoV-2, with most samples with a Ct <30 sequenced. We identified over 150 probable household transmission pairs, where the recipient tested positive 4-9 days after a potential source.
We first analysed intra-host single nucleotide polymorphisms (iSNVs) in >125,000 CIS genomes to identify commonly occurring low allele frequency ‘artefactual’ iSNVs that are unlikely to reflect transmission. Masking these sites, we used consensus differences and iSNV patterns to identify pairs with high-confidence direct transmission. From these pairs, we identified several genomic characteristics which differentiated sources from recipients. Sources typically exhibited higher π diversity, especially in samples collected on the same day; mutational signatures were asymmetrical (e.g., more C->T mutations); and consensus differences usually deviated from population-level consensus.
These findings allowed us to confirm transmission and ascertain the likely transmission direction for tens of thousands of additional household pairs in the CIS, where both individuals tested positive on the same day. This appreciably advances our understanding of SARS-CoV-2 transmission in households, contributing to pandemic management strategies.
