Summer Outbreak of Severe RSV-B Disease, Minnesota, 2017 Associated with Emergence of a Genetically Distinct Viral Lineage

Abstract

Background: Respiratory syncytial virus (RSV) typically causes winter outbreaks in temperate climates. During summer 2017, the Minnesota Department of Health received a report of increased cases of severe RSV-B infection.

Methods: We compared characteristics of summer 2017 cases with those of 2014-2018 summers. To understand the genetic relatedness among viruses, we performed high-throughput sequencing of RSV from patients with a spectrum of illness from sites in Minnesota and Wisconsin.

Results: From May to September 2017, 58 RSV cases (43 RSV-B) were reported compared to 20-29 cases (3-7 RSV-B) during these months in other years. Median age and frequency of comorbidities were similar, but 55% (24/43) were admitted to the ICU in 2017 compared to 12% in preceding 3 years (odds ratio, 4.84, P < .01). Sequencing was performed on 137 specimens from March 2016 to March 2018. Outbreak cases formed a unique clade sharing a single conserved nonsynonymous change in the SH gene. We observed increased cases during the following winter season, when the new lineage was the predominant strain.

Conclusions: We identified an outbreak of severe RSV-B disease associated with a new genetic lineage among urban Minnesota children during a time of expected low RSV circulation.

Keywords: molecular epidemiology; respiratory infections; respiratory syncytial virus; viral next-generation sequencing; viral pathogenesis.

Figure 1.

Number of laboratory-confirmed cases of respiratory syncytial virus infection stratified by age (A) and type (B) in Minnesota, by month and year of detection. Shading indicates the period from June to August.

Figure 2.

A, Phylogenetic tree constructed from respiratory syncytial virus (RSV) whole-genome nucleotide sequences of 19 clinical isolates from inpatients and outpatients in Minnesota from March to May 2016 and June to August 2017. Clinical isolates collected from the summer of 2017 are marked with (•) and sequences encoding aspartic acid (D) at position 64 of SH protein are marked with (*). A subset of whole genomes from diverse geographic sites from GenBank are included for reference. B, RSV genome denoting nonsynonymous sequence polymorphisms between 2016 and 2017 cases. The frequency of these point mutations among viruses collected in Minnesota since 2017 is included in parentheses.

Figure 2.

A, Phylogenetic tree constructed from respiratory syncytial virus (RSV) whole-genome nucleotide sequences of 19 clinical isolates from inpatients and outpatients in Minnesota from March to May 2016 and June to August 2017. Clinical isolates collected from the summer of 2017 are marked with (•) and sequences encoding aspartic acid (D) at position 64 of SH protein are marked with (*). A subset of whole genomes from diverse geographic sites from GenBank are included for reference. B, RSV genome denoting nonsynonymous sequence polymorphisms between 2016 and 2017 cases. The frequency of these point mutations among viruses collected in Minnesota since 2017 is included in parentheses.

Figure 3.

A, Phylogenetic tree constructed from nucleotide sequence of the SH gene from 137 clinical specimens collected between March 2016 and March 2018 and from indicated reference sequences in GenBank. The dashed line indicates a cluster SH gene sequences encoding the N64D variant. B, Number of sequences encoding either the asparagine (N) or aspartic acid (D) variant at amino acid 64 of SH protein by month of collection among all patients (n = 137).