Unbiased metagenomic sequencing complements specific routine diagnostic methods and increases chances to detect rare viral strains

Lewandowska, Dagmara W.; Zagordi, Osvaldo; Zbinden, Andrea; Schuurmans, Macé M.; Schreiber, Peter; Geissberger, Fabienne-Desirée; Huder, Jon B.; Böni, Jürg; Benden, Christian; Mueller, Nicolas J.; Trkola, Alexandra; Huber, Michael

Abstract Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations.