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22 Jun 2022

Development and deployment of a genome analysis tool to track seasonal human coronaviruses

The COVID-19 pandemic has demonstrated that we have the ability to perform large-scale genomic surveillance of the SARS-CoV2 virus. Harnessing this capability could allow us to track and learn more about other circulating coronaviruses.

SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, has been sequenced extensively since the early days of the pandemic. This was vital to track the emergence of variants, and to understand how the behaviour of the virus was changing over time – such as becoming more transmissible, or being able to evade our immune system and cause infection despite past infection or vaccination. To date, over eleven million genomes have been logged globally.

Less well known are the other coronaviruses that circulate among us (so-called seasonal coronaviruses), that usually cause the common cold, but can also cause more serious infections. There are four types of this virus: NL63 and 229E (known as alpha species), and OC43 and HKU1 (known as beta species). Nevertheless, these viruses have barely come under the genomics radar. The virus with the most genomes is OC43 – with just a couple of hundred complete sequences, but HKU1 has only about 50 complete genomes.

This lack of data mattered during the COVID-19 pandemic. Scientists and public health researchers looked to data on seasonal coronaviruses for clues about the behaviour and evolution of SARS-CoV-2. They wanted to know which coronaviruses were circulating seasonally, how they spread in a human population, and whether variants were frequently observed. But this paucity of genomic information for common cold viruses is about to change. Dr Patrick McClure, a Senior Research Fellow at the University of Nottingham’s Faculty of Medicine & Health Sciences, and his group have teamed up with Prof Matt Loose, Professor of Developmental and Computational Biology at the same institution, to develop a genomic sequencing pipeline for seasonal human coronaviruses. These viruses are already screened for by some common diagnostic tests performed in clinical microbiology laboratories, which can provide a patient diagnosis – but as Patrick notes, “this does not give any indication about whether the affected person is part of an outbreak in one or more settings”.

It has become very evident over the pandemic that there is much information to be gained from genomic surveillance, which can document the evolution of viruses through the detection of mutations (typos in the genetic message) and recombination (exchange of genetic information between viral strains). One of the barriers to generating such genome data for seasonal coronaviruses has been a lack of funding. “For some viruses, interest in them has been historically quite low, and funding to investigate them difficult to obtain,” says Patrick. COG-UK has provided funding to kick start a new programme of work through an internal grant scheme.

Patrick’s work is based on the premise that we can learn valuable insights by going back to clinical samples stored before the pandemic from people with viral infections, including seasonal coronaviruses. Such surplus diagnostic samples will help to build a better understand of patterns of coronavirus coinfection and evolution, which he proposes will help us be better prepared for the emergence of recombinant viruses. The lab where Patrick works has around 1,000 pre-pandemic samples ready for sequencing. “We’ve got these great methods for sequencing and analysing SARS-CoV-2, but the question is: can we come up with a similar pipeline to look at seasonal coronaviruses?” At the moment, there is no parallel to the GISAID database used for SARS-CoV-2 and influenza, but COG-UK, and other organisations around the world have shown what is possible.

Patrick concludes that “it’s baby steps for these other viruses, but after SARS-CoV-2 it is right to be more ambitious about sequencing all of the viruses we live with that cause human disease.”

COVID-19 Genomics UK (COG-UK)

The COVID-19 Genomics UK (COG-UK) consortium works in partnership to harness the power of SARS-CoV-2 genomics in the fight against COVID-19.

Led by Professor Sharon Peacock of the University of Cambridge, COG-UK is made up of an innovative collaboration of NHS organisations, the four public health agencies of the UK, the Wellcome Sanger Institute and sixteen academic partners. A full list of collaborators can be found here.

The COVID-19 pandemic, caused by SARS-CoV-2, represents a major threat to health. The COG-UK consortium was formed in March 2020 to deliver SARS-CoV-2 genome sequencing and analysis to inform public health policy and to support the establishment of a national pathogen sequencing service, with sequence data now predominantly generated by the Wellcome Sanger Institute and the Public Health Agencies.

SARS-CoV-2 genome sequencing and analysis plays a key role in the COVID-19 public health response by enabling the identification, tracking and analysis of variants of concern, and by informing the design of vaccines and therapeutics. COG-UK works collaboratively to deliver world-class research on pathogen sequencing and analysis, maximise the value of genomic data by ensuring fair access and data linkage, and provide a training programme to enable equity in global sequencing.