Sequencing and Tracking Of Phylogeny in COVID-19

The current Covid-19 pandemic has caused significant strain on the health care system, and an unprecedented Governmental response to stem the spread of the disease through social distancing and self-isolation. Covid-19 is a pneumonia-like severe acute respiratory syndrome (SARS) caused by a virus, SARS-CoV-2, with similarity to the SARS virus responsible for a worldwide outbreak in 2002. Due to the original SARS outbreak, a large body of genomic data exists for SARS coronaviruses, allowing researchers to understand how the new virus SARS-CoV-2 has evolved to be so virulent in humans.

Since the first case identified in Wuhan, China in December 2019, nearly 30 million cases have been identified world-wide, with nearly 1 million deaths seen so far (figures based on https://www.worldometers.info/coronavirus/ on 16/09/20). Since the release of the first SARS-CoV-2 genome sequence in December 2019, over 100,000 genomes have been submitted to the GISAID (Global Initiative in Sharing All Influenza Data) database, which have allowed researchers to explore the epidemiology of the virus and identify multiple distinct clades of the virus.

Whilst testing kits have been designed to target specific genes in the viral RNA, whole genome sequencing of the virus offers increased scope to track the epidemiology of the virus. In addition, through the use of current sequencing technology available from Oxford Nanopore Technologies (ONT), genome scanning can be performed in near real time and allow for identification of specific viral variants within participant samples. As the pandemic continues to spread, understanding the evolution of the virus and its spread across the globe will help researchers to begin to predict the future spread of the virus, estimate the number of worldwide cases, and aid in the development of epidemiological models for estimating a potential end point to the pandemic crisis. In addition, the ability to track mutations in real time allows researchers access to a large body of data to explore in order to identify potential targets for cures and vaccines.

In this project, we aim to use Nanopore sequencing technology, together with the ARTIC Network protocol (https://artic.network), to assemble viral genomes from viral RNA samples extracted through routine testing for COVID-19. These genomic data will be used to identify potential transmission clusters, to identify the spread of the virus within the local region, and will be compared with a global database of such sequences to help develop global maps of transmission. In addition, we will study effects of different strains of the virus on patient outcomes, and how the specific strain of the virus may impact the health care of the participant.

This work is conducted in collaboration with the COVID-19 Genomics (COG) UK Consortium (https://www.cogconsortium.uk/), which has been developed to provide a distributed genomic epidemiological approach to surveillance of the virus in the UK. The consortium is a partnership of NHS organisations, the four Public Health Agencies of the UK, the Wellcome Sanger Institute and a number of academic partners providing genome sequencing expertise, funded by the UK Department of Health and Social Care (DHSC), UK Research and Innovation (UKRI) and the Wellcome Sanger Institute. The power of this critical national initiative comes from the ability to monitor the virus across the UK in near real-time, particularly as lock-down eases, allowing COG-UK to directly impact Public Health through regular reporting

As the virus moves from person to person, it can change and mutate. By looking at these mutations, we can track how the virus has spread like following a family tree, and use this information to understand how the virus moves from person to person and how quickly this is happening.

Using the latest technology, we can look at these sequences almost in real time, providing a powerful way to track the viral spread. By linking this to anonymous information about the patients themselves, we can understand more about the people most at risk of contracting the disease, the effects of measures such as social distancing, identify treatments that show significant impact on outcomes, and see how quickly the virus is changing and adapting.

As lock-down measures begin to ease, surveillance of future waves will be essential as we manage the pandemic until a vaccine has been developed.

An up-to-date phylogenetic map based on all currently available SARS-CoV-2 genome sequences generated by the COG UK consortium can be found at https://microreact.org/project/cogconsortium.