Sequencing and COVID-19: from genomic epidemiology to host response

At London Calling 2021, researchers from around the world shared their experiences using real-time nanopore sequencing to characterise, track, and manage the spread of SARS-CoV-2. Here you can watch all of the COVID-19 sequencing talks again, covering the latest research — from genomic epidemiology and the identification of novel variants, to exploring host response and the identification of potential disease biomarkers.

Nick Loman: Coronavirus genomic surveillance: where have we been, where are we going next?

Nick discussed the adaptation of the Artic Network protocols for rapid deployment of SARS-CoV-2 sequencing, the important role genomic epidemiology has played during the pandemic, and maybe even more importantly, the role it can play during the next pandemic.

Lu Chen: Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

Lu Chen showed that nanopore SARS-CoV-2 sequencing enabled the identification of 35 recurrent mutations in the Sichuan Province, which in turn showed association with 117 clinical phenotypes, suggesting potentially important mutations. The D500-532 deletion identified in the Nsp1 coding region was found to correlate with lower viral load and lower serum IFN-β levels, and isolates with this mutation induced lower IFN-I response in infected cells — a finding they now intend to investigate further using a mouse model.

George Githinji: Establishing a genomic sequencing platform to inform public health response of SARS-CoV-2 in an LMIC

The sequencing of SARS-CoV-2 genomes provides data crucial to tracking the spread of COVID-19 and the diversity of circulating viruses. In low- and middle-income countries, centralised sequencing facilities may not be available due to the prohibitive costs involved, whilst sending off samples for sequencing may involve long turnaround times. George Githinji (KEMRI-Wellcome Trust Research Programme, Kenya) shared how nanopore sequencing was utilised in setting up decentralised genomic surveillance in Kenya and surrounding region, providing information revealing the early introduction and seeding of SARS-CoV-2 which helped to inform public health measures through the COVID-19 pandemic.

Alexander Dilthey: Characterization of SARS-CoV-2 infection clusters in an urban setting based on integrated real-time genomic surveillance, outbreak analysis, and contact tracing

Throughout the COVID-19 pandemic, the importance of sequencing data in identifying variants, understanding transmission patterns, and informing effective public health decision-making has become increasingly clear. Rapid SARS-CoV-2 sequencing and data sharing is crucial to this effort. Alexander Dilthey (Heinrich Heine University Düsseldorf, Germany) evaluated the impact of incorporating nanopore sequencing, together with contact tracing data, into a fully integrated system for SARS-CoV-2 outbreak response. This ‘genomic surveillance’ shed light on viral population structure and previously undetected routes of transmission, demonstrating its potential as a powerful tool to complement contact tracing efforts to help control the spread of a virus.

Rebekah Penrice-Randal: Rapid insight into the host response in patients with COVID-19 or influenza at point of care with nanopore sequencing

In addition to questions surrounding the SARS-CoV-2 virus itself, researchers are using nanopore sequencing to investigate the host response to COVID-19 infection. Rebekah Penrice-Randal used PCR-cDNA sequencing of human clinical research samples to compare the transcriptomic signatures of COVID-19 vs influenza infections, and fatal vs non-fatal cases of COVID-19, resulting in an average of 2.5 million reads per sample. This enabled the identification of differentially expressed genes between the datasets, suggesting differences in host immune response. She then used a mouse model to investigate the transcriptomics of sequential infection of COVID-19 and influenza, to shed light on what would happen in the event of a heavy flu season during the pandemic.

Irina Chelysheva: Application of long-read RNA sequencing to characterise and distinguish between infections: a pathway to novel diagnostics

Bacterial and viral infections are a global concern, particularly in low-resource settings, with the ongoing SARS-CoV-2 pandemic and risk of other emerging infections representing a further threat. Rapid and sensitive identification of the pathogen present is crucial; however, many infectious diseases — such as typhoid fever and SARS-CoV-2 — present with overlapping symptoms, and current tests can be slow or lack sensitivity. To investigate the potential of transcriptome analysis in distinguishing these diseases, Irina Chelysheva (University of Oxford, UK), used a PromethION to perform nanopore cDNA sequencing of blood samples from individuals with COVID-19 and typhoid fever. This revealed immune response signatures specific to each infection, successfully distinguishing between the two, demonstrating the potential of nanopore sequencing for the future development of rapid diagnostics.

Catch up with the rest of the talks from London Calling 2021 online and visit our COVID-19 resource page to find out more about our flexible, real-time sequencing solutions for SARS-CoV-2 whole genome sequencing.