Utility of long read Nanopore sequencing as a tool for rapid insight into the host response in patients infected with SARS-CoV-2 or influenza A virus at point-of-care

Long read sequencing with Nanopore provides a platform for rapid, accessible, and flexible sequencing of nucleic acids, which is advantageous when faced with an outbreak or biological threat, particularly in situations where there is a lack of and/or demands on specific infrastructure. Investigation of the blood transcriptome can provide a snapshot of the systemic responses within a patient with a view to categorise and/or predict disease progression and outcome. For patients infected with SARS-CoV-2, analysis of the blood transcriptome using Illumina short read sequencing showed that there was a delayed adaptive immune response at the transcript level in those that went on to have a fatal outcome, compared to survivors. The profile of transcript expression data could also be used to predict admission to the intensive care unit (ICU). The use of Nanopore sequencing as a tool for rapid insight into the host response was explored using samples taken at point-of-care from patients infected with SARS-CoV-2 or influenza. This was compared to the same samples that had been previously sequenced using Illumina. Although an overall lower abundance of transcripts was identified using Nanopore sequencing in this study, when combined with bioinformatic analysis of expression pathways and functional analysis results, the findings were comparable. This work demonstrated that Nanopore sequencing is a feasible method for gaining rapid insight into the host response, which may contribute to effective patient care and help inform policy decisions in the face of a novel communicable disease, especially in a low-resource setting.