# Genomic surveillance uncovers regional variation in HCV transmission networks in rural United States

## TL;DR

Genomic surveillance reveals how hepatitis C spreads in rural U.S. communities, showing that social factors shape transmission more than individual traits.

## Contribution

The study integrates genomic data with social network insights to uncover regional HCV transmission patterns in rural opioid-affected areas.

## Key findings

- 29.5% of sequenced individuals are linked in HCV transmission clusters.
- Transmission networks persist for over a decade in some regions.
- Social recruitment is a key factor in forming HCV clusters.

## Abstract

Hepatitis C virus (HCV) remains a public health concern in the United States, particularly in rural communities where the opioid epidemic accelerates transmission among people who use drugs (PWUD). Despite this growing burden, the genetic features and transmission dynamics of HCV in these settings are poorly understood. We analyze 692 HCV antibody-positive specimens collected from rural communities in ten U.S. states using amplicon-based deep sequencing and the Global Hepatitis Outbreak and Surveillance Technology (GHOST) platform to reconstruct transmission networks. Among sequenced individuals, 29.5% are linked within clusters. Cluster structure varies by region from sparse networks in Ohio to dense clusters in New England and phylogenetic analyses show that some networks persist for over a decade, indicating sustained transmission. Nearly half of all clusters involve individuals connected through social recruitment, suggesting peer-referral strategies effectively identify transmission chains. Penalized regression retains only a few individual factors including younger age, peer or partner recruitment, illegal income, methamphetamine use, each with modest effects. These findings suggest that clustering is shaped primarily by social and structural contexts rather than individual characteristics and underscore the importance of integrating genomic surveillance with social-network insights to detect emerging HCV clusters and guide targeted interventions in underserved rural communities.

This study explores the genetic structure of hepatitis C virus outbreaks in rural U.S communities affected by the opioid crisis. Analysis of intra-host viral populations from 692 participants reveals hidden transmission networks.