Mapping Sub‐National Respiratory Virus Circulation in Cambodia Using Metatranscriptomic Sequencing: A Multi‐Center Hospital‐Based Surveillance Study
Christina Yek, Jessalyn Sebastian, Sophana Chea, Sreyngim Lay, Mengheng Oum, Lyhourng Long, Sreytouch Chea, Andrea R. Pacheco, Meera Barochia, Piseth Ly, Sokna Ly, Ratanak Sath, Daniel M. Parker, Volodymyr M. Minin, Matthew Chung, Elodie Ghedin, Fabiano Oliveira, Jessica E. Manning, Kimsreng Lean, Chanty Ny, Viseth Long, Kimhor Leang, Virak Yim, Kry Hok, Rithea Leang, Rekol Huy, Savuth Chin, Darapheak Chau, Heng Seng, Sovann Ly, Chanthap LonABSTRACT
Background
Genomic surveillance can guide early detection of and response to emerging epidemics. Metatranscriptomic sequencing was used to investigate sub‐national respiratory virus circulation in Cambodia from 2020 to 2023.
Methods
Nasopharyngeal swabs were collected from individuals aged 2 months to 65 years with influenza‐like illness in four Cambodian hospitals. Metatranscriptomic data were generated by short‐read RNA sequencing. Bernoulli space–time scan statistics were used to identify temporal virus clusters. Bayesian inference of phylogenetic trees was used to compute divergence times for temporally clustered, highly represented viruses (influenza A/H3N2 and B, Betacoronavirus 1 , respiratory syncytial virus [RSV] A and B), and publicly available global influenza virus genomes.
Results
Of 1093 individuals, 499 (45.7%) had detectable respiratory viruses belonging to 68 distinct species. Moderate ( N > 20) discrete time‐clusters were noted of RSV‐A (37 cases), Betacoronavirus 1 (21 cases), RSV‐B (22 cases), and A/H3N2 (30 cases). The posterior median of time to most recent common ancestor ranged from 0.71 years (95% HPD 0.38–1.10) for Betacoronavirus 1 and 1.31 years (95% HPD 0.60–3.20) for A/H3N2, to 2.75 years (1.82–4.26) for RSV‐A and 4.79 years (2.39–7.74) for RSV‐B. A/H3N2 and influenza B virus genomes mapped to clades 3C.2a1b.2a.2a and Victoria 1A.3a.2, respectively, and inter‐mixed with concurrent global strains.
Conclusions
Multiple respiratory viruses circulated at a sub‐national level in Cambodia from 2020 to 2023 despite pandemic disruptions. Influenza virus population diversity decreased during the height of lockdown but recovered in mid‐2022. Re‐emerging influenza strains were distinct from historically circulating strains and clustered with contemporaneous global variants, suggesting multiple external introductions.