# HCV Ghost Sequencing Center

> **NIH NIH U24** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $162,562

## Abstract

PROJECT SUMMARY:
The United States is in the midst of an enormous opioid epidemic. In 2015, more than 52,000 American’s died
due to a drug overdose, over 60% of which were associated with prescription or illicit opioid use. Given that
injection drug use remains the major risk factor for HCV transmission, concomitantly the US has observed a
striking >150% increase in the incidence of HCV between 2010-2013, and a 364% increase in new HCV
infections between 2006 and 2012 in four Appalachian states, most notably in rural areas. As such, there is
urgent need to more strategically detect, prevent, treat and control HCV on a national level.
Under the parent award we built a high-quality, high-throughput HCV next-generation sequencing (NGS) platform
that enabled the generation of HCV HVR1 sequences from over 1,000 patient samples derived from 8 rural study
sites, along with an in-house informatics pipeline capable of validating phylogenetic clustering identified by the
CDC GHOST laboratory. Transmission network analysis of the NGS data showed that the rate of clustering
(likely direct transmission) varied considerably across study sites ranging from 10% to 42%. Across all
geographical sites, genotype 1a (57%) was the most common followed by genotype 3a (30%), 2b (9%), 1b (4%)
and mixed genotypes represented less than 5% of cases. The implementation of the GHOST HCV molecular
surveillance technology illustrates that genomic surveillance of HCV in rural communities is feasible and suggest
underlying factors may be influencing the size of transmission networks across sites. Under the parent award
we also examined the feasibility of using dried blood spot (DBS) collection for this application. A pilot study
comprising 14 serum samples revealed that viral populations within DBS were genetically indistinguishable from
viral populations derived from plasma, demonstrating that DBS can capture comparable transmission networks
and viral diversity observed from the traditional collection of serum samples. Thus, DBS can augment traditional
HCV surveillance approaches as a practical and cost-effective alternative to frozen plasma in resource-limited
settings such as rural populations.
Due to the substantial impact of the SARS-CoV-2 pandemic upon both our laboratory work at the Ragon Institute,
and upon our UH3 collaborators providing specimens for our work, many of the initial goals of our application
were not completed. This Administrative Supplement to our U24 application proposes to support the generation
and analysis of additional HCV NGS data for the CDC’s GHOST center to identify HCV transmission links among
persons who inject drugs (PWID); validate the application of dried blood spots for the collection and generation
of transmission links by NGS data; manage the collection and storage of serum samples from HIV- and HCV-
infected participants from the clinical research sites under RFA-DA-17-014; and ship specimens to the CDC for
syphilis testing and phylogenet...

## Key facts

- **NIH application ID:** 10649195
- **Project number:** 3U24DA044801-05S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** TODD M ALLEN
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $162,562
- **Award type:** 3
- **Project period:** 2017-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10649195

## Citation

> US National Institutes of Health, RePORTER application 10649195, HCV Ghost Sequencing Center (3U24DA044801-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10649195. Licensed CC0.

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