Rapid metagenomic next-generation sequencing during an investigation of hospital-acquired human parainfluenza virus 3 infections

Metagenomic next-generation sequencing (mNGS) is increasingly used for the unbiased detection of viruses, bacteria, fungi, and eukaryotic parasites in clinical samples. Whole genome sequencing (WGS) of clinical bacterial isolates has been shown to inform hospital infection prevention practices, but the use of this technology during potential respiratory virus outbreaks has not been taken advantage of. Here, we report on the use of mNGS to inform the real-time infection prevention response to a cluster of hospital-acquired human parainfluenza 3 virus (HPIV3) infections at a children’s hospital. Isolates from 3 patients with hospital-acquired HPIV3 identified over a 12-day period on a general medical unit and 10 temporally-associated isolates from patients with community-acquired of HPIV3 were analyzed. Our sample-to-sequencer time was <24 hours while our sample-to-answer turn-around time was <60 hours with a hands-on time of approximately 6 hours. Eight (2 case isolates and 6 control isolates) of 13 samples had sufficient sequencing coverage to yield whole genomes for HPIV3, while 10 (2 cases and 8 controls) of 13 samples gave partial genomes and all 13 samples had >1 read to HPIV3. Phylogenetic clustering revealed the presence of identical HPIV3 genomic sequence in the two of the cases with hospital-acquired infection, consistent with the concern for recent transmission within the medical unit. Adequate sequence coverage was not recovered for the third case. This work demonstrates the promise of mNGS to provide actionable information for infection control in addition to microbial detection.