Genomic surveillance tracks RSV evolution and identifies mutations in Minnesota

A new study shows that the addition of respiratory syncytial virus (RSV) in Minnesota‘The Viral Genomic Surveillance Program demonstrates that prospective respiratory pathogen monitoring can identify the emergence of important mutations and clades.

Researchers from the Minnesota Department of Health (MDH), who published the you find yesterday to Emerging infectious diseasesperformed whole-genome sequencing of 575 respiratory samples collected from hospitalized and non-hospitalized RSV patients at 11 state health centers from July 2023 to February 2024. Median patient age was 2 years, 91 .8% were adults, 53.4% ​​were women and 5% were 65 years or older.

“Researchers have applied whole genome sequencing (WGS) for retrospective RSV surveillance and outbreak investigation in the United States, but WGS has not yet been documented as a tool for prospective surveillance,” they wrote.

A clade has a resistance gene

Sequencing classified 287 (49.9%) genomes as subgroup A and 288 (50.1%) as subgroup B. The majority of RSV-A genomes (98.9%) were distributed in four lineages of whole genome (AD1, 10.8%; AD3, 18.5%; AD5). , 38.0% and AD5.2, (31.7%), while 95.1% of RSV-B genomes belonged to the BDE1 lineage.

The detection of clusters within the viral population shows the potential use of WGS for detection and investigation of RSV outbreaks at the state or local level.

Comparisons of plots depicting evolutionary relationships showed greater diversity among all RSV-A genomes than among RSV-B genomes. Timescale-specific phylogenetic analyzes of the sequenced genomes estimated that the divergence of the lineages occurred 2–8 years before their first specimen collections.

The team identified single nucleotide polymorphisms (SNPs; a type of mutation), with pairwise comparisons showing that 32.3% of genomes were identical to at least one other genome, while 53% had a SNP . Twenty-three clusters of three or more genomes were identical, including 19.5% of all genomes.

An eight-genome clade of RSV-B had a mutation linked to resistance to the RSV monoclonal antibody nirsevimab (Beyfortus). The most recent common ancestor of this clade probably circulated in the fall of 2023.

To assess their ability to link RSV genomes to known serious infections, the researchers cross-referenced the names and birth dates of RSV patients with samples sequenced with the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV- NET) of the Centers for Disease Control and Prevention.

Of the 531 genomes collected from October 2023 to January 2024, the peak months of specimen collection, 22% were found in RSV-NET cases, representing 6.3% of all hospitalizations by RSV during this period. Nine (39.1%) of the 23 clusters included one or more cases of RSV-NET, and 13.4% of clustered cases were in RSV-NET.

Two RSV-NET patients with sequenced RSV AD5.2 infections had received nirsevimab. Of the eight RSV-B patients whose genomes carried the nirsevimab resistance gene, one was found to be RSV-NET.

Potential role in outbreak investigation

The findings “show that the application of WGS for RSV surveillance can provide information on viral circulation and population dynamics,” the authors wrote. “The detection of clusters within the viral population shows the potential use of WGS for detection and investigation of RSV outbreaks at the state or local level. Our study also provided new cross-references of viral genomic data against clinical surveillance sentinel of severe RSV infections”.

The team cautioned that their “biased and localized convenience sample limited the analytic potential of our findings. The limited geographic and temporal scope of our study could also introduce variability in our time-scale analyzes and site-specific discrepancies.” the location between the evolution of RSV in Minnesota and in other regions.”

The researchers said they will expand their genomic and epidemiological data with more specific collection of specimens and perform sufficiently powered epidemiological analyzes of the occurrence of mutations associated with vaccine escape, virulence and transmissibility.