Metagenomic Sequencing of Viral Outbreak Reveals Transmission Clusters

genome sequencing
genome sequencing
Metagenomic sequencing identified genetically distinct, chronologically overlapping case clusters during a hospital-associated norovirus outbreak.

Real-time metagenomic sequencing identified genetically distinct, chronologically overlapping case clusters during a hospital-associated norovirus outbreak and further showed that after the epidemiologically defined outbreak had ceased, ongoing transmission and shedding of outbreak-associated virus occurred. The outbreak description, sequencing results, and associated retrospective cohort study data were published in Clinical Infectious Diseases.

The hospital-associated norovirus outbreak affected 13 patients over a period of 27 days in a tertiary-care pediatric hospital. This outbreak was chronologically associated with a spike in self-reported gastrointestinal symptoms among staff members. The real-time metagenomic sequencing of norovirus genomes revealed 10 chronologically overlapping hospital-acquired cases that were partitioned into 3 distinct transmission clusters. Study investigators also found close genetic relationships between some hospital-acquired and community-acquired cases and chronic viral shedding by a patient who is immunocompromised who acquired the virus in the hospital. Serial samples of norovirus from this patient also provided novel insights into the evolution of norovirus within an immunocompromised host.

There were several limitations to this study, including an inability to collect samples from sick hospital staff, as well as the retrospective nature of the work. Study investigators also noted some technical limitations, such as a failure to recover genomes from some samples as a result of variable viral RNA quality and quantity of the clinical samples. Further, because of the cost of reagents for the Illumina sequencing platform, laboratories use them in batched sequencing processes, which limited the ability to perform true real-time analysis in this study.

According to the study authors, this was one of the first applications of real-time metagenomic next-generation sequencing during a hospital-associated viral outbreak and it shows, “how metagenomics methods can be employed in outbreak investigations to elucidate intricate details about pathogen transmission.” Researchers concluded that these results show the importance of these interventions to prevent transmission of pathogens in health care settings, particularly for norovirus, which is highly contagious and has lasting impacts on medical systems and vulnerable patient populations.

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Casto AM, Adler AL, Makhsous N, et al. Prospective real-time metagenomic sequencing during norovirus outbreak reveals discrete transmission clusters [published online December 4, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy1020