Respiratory virus transmission in healthcare settings is not well understood. To investigate the transmission dynamics of common healthcare-associated respiratory virus infections, we performed retrospective whole genome sequencing (WGS) surveillance at three teaching hospitals.

From January 2, 2018, to January 4, 2020, nasal swab specimens positive for rhinovirus, influenza virus, human metapneumovirus (HMPV), or respiratory syncytial virus (RSV) from patients hospitalized for ≥3 days were sequenced. High-quality genomes were assessed for genetic relatedness using ≤3 single nucleotide polymorphisms (SNPs) as a cutoff, except for rhinovirus (≤10 SNPs). Patient health records were reviewed for genetically related clusters to identify epidemiological connections.

We collected 436 viral specimens from 359 patients: rhinovirus (n = 291), influenza virus (n = 50), RSV (n = 48), and HMPV (n = 47). Of these, 42%% (152/359 patients) were from a pediatric hospital, and 58% were from adult hospitals. WGS was performed on 61.2% (178/291) rhinovirus, 78% (39/50) influenza virus, 90% (43/48) RSV, and all HMPV specimens. Among high-quality genomes, we identified 14 genetically related clusters involving 36 patients (range: 2–5 patients per cluster). We identified common epidemiological links for 53% (19/36) of clustered patients; 63% (12/19) of patients had same-unit stays, 26% (5/19) had overlapping hospital stays, and 11% (2/19) shared common providers. On average, genetically related clusters spanned 16 days (range: 0 − 55 days).

WGS offered new insights into respiratory virus transmission dynamics. These advancements could potentially improve infection prevention and control strategies, leading to enhanced patient safety and healthcare outcomes.