Explainer: The COVID-19 genome
What studying the virus' genomes can tell us about the pandemic
More than 20,000 SARS-CoV-2 that have caused infection in people in the UK have been sequenced by the Covid-19 Genomics UK (COG-UK) Consortium to date. Analysing these and future sequences will help create the evidence for how to use these as a vital part of controlling the pandemic.
Information from the genome sequences will help track the spread of the coronavirus in the UK and support public health planning and clinical decision making.
In such a fast-moving situation, careful interpretation of information from genome sequences, together with additional data, is essential. Here, we reflect on what the genome data can, and can’t, tell us.
Virus genomes are not made of DNA like most organisms, but RNA. The genome sequence of the SARS-CoV-2 virus was determined several months ago after it was first detected in China. It is small, at just under 30,000 letters, or bases (29 kilobases), with only 15 genes. Humans, by comparison, have around 20,000 genes in a 3 billion base pair (3.3 gigabase) genome. More about COVID-19 biology is available on the UKRI website.
Why sequence genomes of the SARS-CoV-2 virus?
Building genome-based trees to define transmission
Genomes mutate. Letters in the genome sequence change as organisms replicate. Virus genomes usually mutate at a steady rate – HIV extremely rapidly, influenza slower, and coronavirus slower still. Researchers can use the mutation rate as a molecular clock. Any genetic difference between two viruses is proportional to the time since they last shared a common ancestor. The individual virus sequences can be placed back in time on a phylogenetic tree, much like a family tree, which determines the relatedness of two or more SARS-CoV-2 viruses.
With a new virus, it is hard to initially define how fast the clock is ticking. The SARS-CoV-2 mutation rate was initially based on that of related viruses, though researchers now estimate it has a mutation rate of approximately 2.5 bases a month – slow in evolutionary terms.
Together with the fact that the virus has a very recent common ancestor – in December 2019 – the slow mutation rate means that there is limited genomic diversity in the circulating viruses so far, although that will change over time as mutations accumulate. Despite this, it has been possible to trace the virus’s history, from the centre of the outbreak, to all corners of the world. Researchers are constantly refining and updating the picture as more evidence becomes available. To view global data for SARS-CoV-2 to date, visit https://nextstrain.org/ncov/global.
The same principles of building a phylogenetic tree can be used on a more local scale, too. The virus in a particular area, be that a hospital, town, or region, may have a particular genomic change. This change may be different from a virus that is multiplying and spreading in another area. If a third area is tested, researchers can, in some cases, trace where it has come from, based on its sequence.
COG-UK researchers envisage that we will soon be at this point in the UK, where they will have accumulated enough data to see ‘local’ mutations in the virus. If sequencing can be done in real-time, then this is important information for public health officials – outbreaks can be spotted and brought to a rapid close, as well as other interventions being introduced to reduce the chances of this happening again.
Recent research led by Professor Ian Goodfellow and Dr Estée Török at the University of Cambridge assessed how useful genomic sequencing of the virus can be within a hospital. They assessed hundreds of virus sequences from Cambridge University Hospitals NHS Foundation Trust during March and April. Together with data about the movement of patients and staff, they were able to identify clusters of infections that were linked, and some that weren’t. This, in turn, helped inform infection control procedures. The genomic data provided evidence to support or refute transmission between potentially linked cases.
But caution is needed when interpreting such data. Sequences from two or more people could be the same through chance rather than because they are part of an outbreak. Other information, such as whether the people involved have been in direct contact or shared the same environment, is an essential part of the process when investigating possible outbreaks.
As a result, it is easier to rule out outbreaks when people with covid-19 have viruses are genetically distinct than it is to confirm an outbreak when genomes are the same. Extensive spread of the virus means that identical genomes can be seen even in different countries despite the lack of a direct epidemiological link.
An important pitfall is when not enough sequences are used in an outbreak analysis. This can lead to false connections being made between genomes, which when more sequences are added to the analysis can become more distantly related. Genomic analysis is a dynamic process and will depend on having the right number and sampling strategy.
Array ( [secondary_title] => Read the Wellcome Sanger Insitute's Blog post about their work and watch their video [excerpt] => Read the Wellcome Sanger Insitute's Blog post about their work and watch their video [byline_text] => Blog post and video by the Sanger Institute, a COG-UK Consortium partner [byline_date] => 20201023 [main_image] => 1221 [teaser_image] => [content] => In a <strong><a href="https://sangerinstitute.blog/2020/10/22/sequencing-covid-19-at-the-sanger-institute/" target="_blank" rel="noopener">blog post</a></strong> and <strong><a href="https://youtu.be/Fd40gunBTN0" target="_blank" rel="noopener">video</a></strong>, the Wellcome Sanger Institute takes you behind the scenes of its work to provide large-scale genome sequencing of thousands of COVID-19 samples as part of the COVID-19 Genomics UK (COG-UK) consortium. To read the blog post, please click here: <strong><a href="https://sangerinstitute.blog/2020/10/22/sequencing-covid-19-at-the-sanger-institute/" target="_blank" rel="noopener">Sequencing COVID-19 at the Sanger Institute</a></strong> The video is available below: <iframe src="https://www.youtube.com/embed/Fd40gunBTN0" width="560" height="315" frameborder="0" allowfullscreen="allowfullscreen"></iframe> [options_news_type] => Blog [options_exclude_from_feeds] => 0 [ID] => 1220 [post_title] => How a COG-UK Partner is helping to sequence tens of thousands of COVID-19 samples [post_type] => news_item [post_excerpt] => [post_content] => [post_url] => https://www.cogconsortium.uk/news_item/how-a-cog-uk-partner-is-helping-to-sequence-tens-of-thousands-of-covid-19-samples/ [post_name] => how-a-cog-uk-partner-is-helping-to-sequence-tens-of-thousands-of-covid-19-samples [created_at] => 2020-10-23 14:50:41 [updated_at] => 2020-10-23 14:50:41 [large_image_url] => /wp-content/uploads/2020/10/covid_sanger_blog-1024x391.jpg [main_image_url] => /wp-content/uploads/2020/10/covid_sanger_blog-1024x391.jpg [main_image_caption] => Wellcome Sanger Institute [image_string] => src="/wp-content/uploads/2020/10/covid_sanger_blog-1024x391.jpg" class="news-image" style="object-fit: cover" )
How a COG-UK Partner is helping to sequence tens of thousands of COVID-19 samples
Read the Wellcome Sanger Insitute's Blog post about their work and watch their video
Array ( [secondary_title] => Commentary for report 12 – 15th October 2020 [excerpt] => As of 22nd October, the COVID-19 Genomics UK (COG-UK) Consortium has sequenced more than 81,000 SARS-CoV-2 virus genomes from the UK, representing about 45 per cent of the global total. [byline_text] => Commentary [byline_date] => 20201023 [main_image] => 1225 [teaser_image] => [content] => As of 22<sup>nd</sup> October, the COVID-19 Genomics UK (COG-UK) Consortium has sequenced more than 81,000 SARS-CoV-2 virus genomes from the UK, representing about 45 per cent of the global total. Report 12 presents details of three separate studies using the genome data, and a summary of nationwide outbreak investigations that have used COG-UK genome data. The information shows the ongoing state of the research, and has not been peer-reviewed. Conclusions may change as more evidence becomes available. The first study is into a genetic mutation of the virus, termed N439K. This mutation results in a change to the Spike protein of the virus – the protein it uses to enter human cells. Because of its location, this mutation could affect a person’s immune response to the virus. The report stresses the need for systematic monitoring of virus mutations, especially when vaccinations begin. The second study details the use of viral genomic data in Norfolk, where the data has enabled local outbreak management. The third study assessed respiratory disease in cats, associated with human-to-cat transmission of SARS-CoV-2. Finally, there is a summary showing COG-UK data and tools have been used in over 120 SARS-CoV-2 outbreak investigations in the UK. <h3>N439K Mutation</h3> Researchers around the world have been monitoring genetic changes in the virus, which accumulate as it replicates and transmits. The aim is to understand if any changes, or mutations, have an effect on the virus’s function, the severity of disease it causes, or transmission. So far, no mutation seen has altered the disease severity that the virus causes. There is a focus on changes that affect the virus’s characteristic Spike protein. Like all coronaviruses, the SARS-CoV-2 virus has proteins that stick out of its core. These Spike proteins are the ‘crowns’ that give coronaviruses their name. It is this protein that allows the virus to attach to, and then enter, human cells. Any mutations that affect the Spike protein are vital to monitor, as they could potentially affect its function. It is also a part of the virus that our immune systems can ‘see’ and respond to. It <a href="https://www.cogconsortium.uk/news_item/commentary-cog-uk-report-9-25th-june-2020/">was reported previously</a> that a mutation in the Spike protein called D614G has increased in circulating viruses, in a way that is consistent with a slight increase in the rate of transmission. COG-UK researchers, led by <a href="https://www.gla.ac.uk/researchinstitutes/iii/staff/davidrobertson/">Professor David Robertson</a> and <a href="https://www.gla.ac.uk/researchinstitutes/iii/staff/emmathomson/">Professor Emma Thomson</a> at the University of Glasgow, assessed all mutations in the Spike protein. One of these - N439K – was of particular interest. N439K results in a change to the part of the Spike protein that binds to human cells. It is stable in the current virus population; it was seen in over 500 samples in Scotland early on in the UK epidemic, but then died out following the lockdown in March. It is now present again in virus samples from across Europe, the UK and the US. The wide spread of this mutation indicates the virus can thrive with such mutations – there is no detriment to its function. Once vaccinations begin at scale, the Spike protein will be under ‘selective pressure’, as many vaccines are targeted against it. It is possible that viruses with certain mutations will fare better under a vaccine-primed immune response than others. Ongoing, early-stage, laboratory studies support this hypothesis. Work has shown that virus with the N439K mutation is able to resist monoclonal antibodies – like those being trialled as treatments - yet still bind to its target on human cells. But unlike a monoclonal antibody treatment, vaccines will prompt the immune system to make a range of antibodies, and so even if the Spike protein can resist one, it is likely another will be able to neutralise the virus. The researchers stress the importance of systematically monitoring Spike protein mutations, finding and assessing new ones to understand their effects. This will be essential in the run up to any vaccine being introduced. The COG-UK team has set up a group, and systems, with the dedicated aim of monitoring new and existing mutations, prioritising those that need in-depth analyses. <h3>Local Outbreak Management</h3> Researchers led by <a href="https://quadram.ac.uk/people/andrew-page/">Dr Andrew Page at the Quadram Institute</a> in Norwich, report on the analysis of 1,035 SARS-CoV-2 genomes collected in Norfolk between March and August 2020. They combined genome sequence data with clinical data to understand the origin, genetic variation, transmission and spread of SARS-CoV-2 in the region. They confirmed an outbreak at a food-processing facility and ruled out a hospital setting as the source of another outbreak. Long term follow up found no evidence of reinfection. The team also found 16 viral variants, or lineages, in health care workers that were not present in patients, showing that PPE and infection control measures work to stop transmission of the virus. For full details, view the study on <a href="https://doi.org/10.1101/2020.09.28.20201475">MedRxiv</a>. <h3>Human to cat transmission</h3> <a href="https://www.gla.ac.uk/researchinstitutes/iii/staff/margarethosie/">Professor Margaret Hosie at the University of Glasgow</a> and colleagues looked at transmission of SARS-CoV-2 between humans and cats. Two cats from different COVID-19 infected households in the UK were shown to be infected with SARS-CoV-2 from humans. There is no evidence of cat-to-human transmission, or that any domestic animals play a role in the epidemiology of human infections with SARS-CoV-2. For full details, view the study on <a href="https://www.biorxiv.org/content/10.1101/2020.09.23.309948v1.full">BioRxiv</a>. <h3>Summary of studies using COG-UK genomic data</h3> COG-UK data and tools have been used in more than 120 live and retrospective SARS-CoV-2 outbreak investigations. This includes outbreaks in hospitals, communities, workplaces and settings managed by local authorities. For examples, see ‘<a href="https://www.cogconsortium.uk/wp-content/uploads/2020/09/8th-September-2020-Report-COVID-19-Genomics-UK-COG-UK-Consortium.pdf">COG-UK genomic surveillance in action</a>’. As the speed and scale of SARS-CoV-2 genome sequencing increases, the ability to use genomic data to investigate a wide range of scientific and public health questions is also growing. COG-UK aims to provide a large scale genomic surveillance service to support the investigation of more live outbreaks in the UK. [options_news_type] => Blog [options_exclude_from_feeds] => 0 [ID] => 1215 [post_title] => Commentary: COG-UK report 12 – 15th October 2020 [post_type] => news_item [post_excerpt] => [post_content] => [post_url] => https://www.cogconsortium.uk/news_item/commentary-cog-uk-report-12-15th-october-2020/ [post_name] => commentary-cog-uk-report-12-15th-october-2020 [created_at] => 2020-10-23 09:35:37 [updated_at] => 2020-10-24 05:37:41 [large_image_url] => /wp-content/uploads/2020/10/commentary_from_cogUK-1024x391.jpg [main_image_url] => /wp-content/uploads/2020/10/commentary_from_cogUK-1024x391.jpg [main_image_caption] => Hannah Olinger on Unsplash.com [image_string] => src="/wp-content/uploads/2020/10/commentary_from_cogUK-1024x391.jpg" class="news-image" style="object-fit: cover" )
Commentary: COG-UK report 12 – 15th October 2020
As of 22nd October, the COVID-19 Genomics UK (COG-UK) Consortium has sequenced more than 81,000 SARS-CoV-2 virus genomes from the UK, representing about 45 per cent of the global total.
Array ( [secondary_title] => <b>Please Note:</b> This report is provided at the request of SAGE and includes information on the ongoing state of the <span title="... research being carried out. It should not be considered formal or informal advice. The conclusions of the ongoing scientific studies may be subject to change as further evidence becomes available and as such any firm conclusions would be premature.">...</span> [excerpt] => COG-UK genome sequence data and tools have been used in more than 120 retrospective and live public health outbreak investigations in the UK since March 2020. Analysis of COG-UK and GISAID data highlights the need to establish a systematic approach for monitoring the appearance and spread of all variants of the SARS-CoV-2 virus [byline_text] => Report by the COVID-19 Genomics UK (COG-UK) Consortium [byline_date] => 20201016 [main_image] => 1183 [teaser_image] => [content] => <h2>Executive Summary</h2> <ul> <li>COG-UK genome sequence data and tools have been used in more than 120 retrospective and live public health outbreak investigations in the UK since March 2020.</li> <li>A viral lineage carrying a mutation, N439K, a probable antigenic variant owing to its location in the receptor binding motif of the SARS-CoV-2 spike protein, is now spreading in Europe (including 500+ infections in the UK). While there is no evidence that this variant will affect the efficacy of vaccines currently in development, it does highlight the need to establish a systematic approach for monitoring the appearance and spread of all variants and prioritising mutations of interest for further characterisation, in particular when selective pressure from mass vaccination programmes begins.</li> </ul> <hr /> <h2>COG-UK summary</h2> As described in <a href="https://www.cogconsortium.uk/wp-content/uploads/2020/09/8th-September-2020-Report-COVID-19-Genomics-UK-COG-UK-Consortium.pdf">COG-UK Report #11</a>, in addition to retrospective investigations, the consortium has been providing crucial support for the genomic surveillance of active SARS-CoV-2 outbreaks. An email survey of COG-UK site leads was used to collate information on the number of outbreaks in which investigations by the consortium using genomics have added value (Table 1). In total, COG-UK data and tools have been used in 120-166 live and retrospective SARS-CoV-2 outbreak investigations in public health and hospital settings in the UK to date. [caption id="attachment_1162" align="aligncenter" width="1024"]<a href="https://www.cogconsortium.uk/wp-content/uploads/2020/10/table1.jpg"><img class="wp-image-1162 size-large" src="https://www.cogconsortium.uk/wp-content/uploads/2020/10/table1-1024x143.jpg" alt="" width="1024" height="143" /></a> <strong>Table 1:</strong> A summary of live and retrospective outbreaks in the UK for which COG-UK and PHA researchers have used consortium genomic data and tools. Exceedance describes defined outbreaks, for instance in a workplace. Surveillance programmes describe requests to look at everything in a local authority area, school, care home etc. Ranges are reported as some sites were only able to provide estimates.[/caption] For a description of specific examples of the value added through the use of genomics by consortium members during outbreak investigations see <a href="https://www.cogconsortium.uk/wp-content/uploads/2020/09/8th-September-2020-Report-COVID-19-Genomics-UK-COG-UK-Consortium.pdf" target="_blank" rel="noopener">‘COG-UK genomic surveillance in action’, COG-UK Report #11</a>. As the transition to a new operational phase continues through late 2020 and into 2021, COG-UK will provide large scale genomic surveillance service to support the investigation of a growing proportion of live outbreaks in the UK. As described in the recent NERVTAG paper to SAGE, co-authored by COG-UK (<em>Is there evidence for genetic change in SARS-CoV-2 and if so, do mutations affect virus phenotype?</em>), there is increasing interest in monitoring mutations arising in the SARS-CoV-2 genome and determining whether these mutations have an impact on the biology of the virus, its transmission and the severity of the disease that it causes (See also ‘<em>A preliminary analysis of SARS-CoV-2 spike protein N439K lineages and surveillance of receptor binding mutations.</em>’ below). A COG-UK working group is being established to ensure that new and existing mutations are monitored in a systematic manner and that mutations of particular interest are prioritised for in depth analysis. As the speed and scale of SARS-CoV-2 genome sequencing increases, the ability to use genomic data to investigate a wide range of scientific and public health questions is also growing. Accordingly, COG-UK is strengthening its interactions with other SAGE sub-groups, research consortia and public health bodies in the UK, and globally, so that the opportunities provided by integrating genomics can be realised. Dr Andrew Page of the Quadram Institute, Norwich has recently agreed to represent COG-UK on the SAGE sub-group focussed on social care homes. Dr Ewan Harrison of the Wellcome Sanger Institute represents the consortium on the sub-group focussed on ethnicity, and Professor Judith Breuer of University College London on the nosocomial infection sub-group. All five Health and Social Care Trusts in Northern Ireland are joining the SIREN study (the PHE priority study to determine if prior SARS-CoV-2 infection in health care workers confers future immunity to re- infection), and the Belfast Health and Social Care Trust is expected to join COG-UK’s Hospital-Onset COVID-19 Infections study. Northern Ireland will therefore be represented in both of these important UK-wide studies, with viral genome sequencing/analysis via COG-UK. <hr /> <h2>Analysis updates</h2> <h3>A preliminary analysis of SARS-CoV-2 spike protein N439K lineages and surveillance of receptor binding domain mutations.</h3> <h4>Study leads</h4> David L Robertson<sup>1</sup>, Sebastian Maurer-Stroh<sup>2</sup>, Ana da Silva Filipe<sup>1</sup> and Emma C Thomson<sup>1</sup> 1. MRC-University of Glasgow Centre for Virus Research; 2. Bioinformatics Institute, Agency for Science, Technology and Research, Singapore <h4>Question addressed</h4> SARS-CoV-2 is continually accruing mutations as it replicates and transmits among the human population. While the majority of observed mutations have no effect on the biological properties of the virus and the rate of change is relatively slow, it is important that there is a systematic approach to identify new genetic changes and to assess their biological significance. While much attention has been focussed on the SARS-CoV-2 spike protein D614G mutation (See <a href="https://www.cogconsortium.uk/wp-content/uploads/2020/05/14th-May-2020-Report-COVID-19-Genomics-UK-COG-UK-Consortium.pdf" target="_blank" rel="noopener">COG-UK report #6</a>, <a href="https://www.cogconsortium.uk/wp-content/uploads/2020/07/25th-June-2020-Report-COVID-19-Genomics-UK-COG-UK-Consortium.pdf" target="_blank" rel="noopener">report #9</a> and Ref 1), other mutations in the spike protein may be of epidemiological and clinical relevance. This analysis describes the assessment of transmission and likely biological significance of one such mutation: N439K in the spike receptor binding motif is an example of a stable and circulating mutation in the receptor binding motif that binds to the ACE2 receptor on the surface of host cells to enable viral entry. <h4>Methodology</h4> Preliminary assessment of sampling proportions, phylogenetic distribution and the relationship between N/K at position 439 of the spike protein. <h4>Findings</h4> N439K was initially identified in a single lineage first detected in March 2020 and until recently was almost unique to Scotland where it infected more than 500 individuals (Figure 1). [caption id="attachment_1163" align="aligncenter" width="1024"]<a href="https://www.cogconsortium.uk/wp-content/uploads/2020/10/phylogenetic_tree_5000_scottish_genomes.jpg"><img class="wp-image-1163 size-large" src="https://www.cogconsortium.uk/wp-content/uploads/2020/10/phylogenetic_tree_5000_scottish_genomes-1024x395.jpg" alt="" width="1024" height="395" /></a> <strong>Figure 1:</strong> Phylogenetic tree of 5000 Scottish SARS-CoV-2 genomes from COG-UK dataset (17/07/20) highlighting D614G lineages (left panel) and N439K lineages (right panel). Note that the K-439 lineage and most N-439 lineages are also G-614.[/caption] This lineage also carries the D614G variant that has been associated with an increase in frequency among the population. In line with the cessation in viral transmission in Scotland coincident with the lockdown in spring 2020, this UK lineage is now extinct and has not been observed since the 20th June in South Lanarkshire. However, N439K has now been identified in another fast growing lineage that has been sampled between late June and mid-August in Romania, Norway, Switzerland, Ireland, Belgium, Germany and now in all parts of the UK (Figure 2). The apparent sudden rise in August/September appears to be linked to relaxation of control measures, the degree of sampling in these countries and its recent emergence in the UK with a high sampling rate. N439K has also been detected in four linked infections in the US and sporadically in genome data from elsewhere. [caption id="attachment_1164" align="aligncenter" width="1024"]<a href="https://www.cogconsortium.uk/wp-content/uploads/2020/10/phylogenetic_gisaid.jpg"><img class="wp-image-1164 size-large" src="https://www.cogconsortium.uk/wp-content/uploads/2020/10/phylogenetic_gisaid-1024x551.jpg" alt="" width="1024" height="551" /></a> <strong>Figure 2:</strong> A) Phylogenetic tree of SARS-CoV-2 genomes from the COG-UK data in the context of the GISAID dataset highlighting the original Scottish N439K lineage and the more recent and currently spreading European N439K lineage associated with multiple UK lineages. B) Number of weekly cases and country location of the two N439K lineages from mid-March to 02/10/2020.[/caption] Investigation of clinical outcomes from >1600 Scottish patients infected with either the lineage defined by 439K versus the wild-type lineage (439N) showed no significant difference in disease severity. Phylodynamic analysis demonstrated that the Scottish N439K lineage has a relatively fast growth rate in spreading through the population (analysis by Sam Lycett, Roslin Institute), but this is likely due to the D614G background of this lineage (Ref 1). Competitive virus growth experiments of these different mutants are underway at the MRC-University of Glasgow Centre for Virus Research. Investigation of clinical outcomes from >1600 Scottish patients infected with either the lineage defined by 439K versus the wild-type lineage (439N) showed no significant difference in disease severity. Phylodynamic analysis demonstrated that the Scottish N439K lineage has a relatively fast growth rate in spreading through the population (analysis by Sam Lycett, Roslin Institute), but this is likely due to the D614G background of this lineage (Ref 1). Competitive virus growth experiments of these different mutants are underway at the MRC-University of Glasgow Centre for Virus Research. <h4>Key Conclusions</h4> While SARS-CoV-2 genetic variation is accumulating, it is relatively constrained for an RNA virus. Some spike amino acid replacements do seem to be changing the biology of the virus (e.g. D614G), although there is no current evidence that N439K, or other variants in the receptor binding motif (such as T478I and V483I, shown to have antigenic significance) have increased the potential for transmission or altered disease severity. Importantly, these spike receptor binding domain variants appear to be relatively stable amino acid replacements that are not detrimental to viral fitness and are well tolerated in circulating lineages in the UK. This is a potential concern as vaccination programmes designed using these regions as targets begin to apply selective pressure on these lineages (see below for further discussion). <h4>Discussion</h4> In addition to N439K, other mutations are being observed in the spike receptor binding motif: S477N (>300 UK sequences), T478I (>100), S494P (>20), E484Q (>10), S477I (>10), E484Q (>10) and others at lower frequencies (Figure 3). [caption id="attachment_1165" align="aligncenter" width="1024"]<a href="https://www.cogconsortium.uk/wp-content/uploads/2020/10/fig3.jpg"><img class="wp-image-1165 size-large" src="https://www.cogconsortium.uk/wp-content/uploads/2020/10/fig3-1024x715.jpg" alt="" width="1024" height="715" /></a> <strong>Figure 3.</strong> Receptor binding surveillance for UK complete genomes. Mutations resulting in amino acid replacements in or near SARS-CoV-2’s spike receptor binding motif that have been observed by 2020-10-06 are shown. Replacements occurring at least twice are listed (top).[/caption] Collectively these demonstrate that mutations in the spike receptor binding motif are tolerated. The circulation of the N439K lineages demonstrates these viruses do not necessarily exhibit any apparent fitness cost. This is potentially concerning as this region is soon to be under selective pressure from a range of vaccine programmes. Some of the mutations in the receptor binding domain have been documented to confer resistance to neutralising antibodies and to influence interactions with the ACE2 receptor, which may facilitate the evolution of additional mutations in the surrounding region that can lead to viruses able circumvent the impact of those neutralizing antibodies. Support for this concern has been provide by laboratory experiments showing that it is possible to select for SARS-CoV-2 spike protein mutations in the receptor-binding domain (including N439K) that remain functional and able to bind ACE2 receptors but can confer resistance to monoclonal neutralising antibodies or convalescent plasma (Refs 2 and 3). It is therefore essential that a systematic approach is taken to identify and assess new genetic changes, in particular in regions important for host infection, viral transmission and for antigenicity. Whilst limited genomic diversity has emerged to date, this may change in the next phase of the epidemic as selective pressures exerted by vaccines, treatments and non-pharmaceutical interventions increases. As such, it is particularly important that surveillance of antigenic change is established in the lead up to the roll out of a vaccination program in the UK, since many of the vaccines under development target the spike protein. Accordingly COG-UK has established a working group to establish a mechanism to ensure that new and existing mutations are monitored in a systematic manner and that mutations of particular interest are prioritised for in depth genomic, phylodynamic and virological analyses. <h4>References</h4> 1. Volz, E. M, <em>et al</em>. Evaluating the effects of SARS-CoV-2 Spike mutation D614G on transmissibility and pathogenicity (2020) <em>medRxiv</em>, doi: <a href="https://doi.org/10.1101/2020.07.31.20166082" target="_blank" rel="noopener">https://doi.org/10.1101/2020.07.31.20166082</a>. 2. Weisblum, Y., Schmidt, F., <em>et al</em>. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. (2020) <em>bioRxiv</em>, doi: <a href="https://doi.org/10.1101/2020.07.21.214759" target="_blank" rel="noopener">https://doi.org/10.1101/2020.07.21.214759</a>. 3. Li, Q. <em>et al</em>. The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity. (2020) <em>Cell</em>, doi: <a href="https://doi.org/10.1016/j.cell.2020.07.012" target="_blank" rel="noopener">https://doi.org/10.1016/j.cell.2020.07.012</a> <hr /> <h2>COG-UK recent publications</h2> <h3>Large scale sequencing of SARS-CoV-2 genomes from one region allows detailed epidemiology and enables local outbreak management</h3> <em>MedRxiv</em> - doi: <a href="https://doi.org/10.1101/2020.09.28.20201475" target="_blank" rel="noopener">https://doi.org/10.1101/2020.09.28.20201475</a> <h4>Authors:</h4> Andrew J Page, Alison E Mather, Thanh Le Viet, Emma J Meader, Nabil-Fareed J Alikhan, Gemma L Kay, Leonardo de Oliveira Martins, Alp Aydin, David J Baker, Alexander J. Trotter, Steven Rudder, Ana P Tedim, Anastasia Kolyva, Rachael Stanley, Maria Diaz, Will Potter, Claire Stuart, Lizzie Meadows, Andrew Bell, Ana Victoria Gutierrez, Nicholas M Thomson, Evelien M Adriaenssens, Tracey Swingler, Rachel AJ Gilroy, Luke Griffith, Dheeraj K Sethi, Rose K Davidson, Robert A Kingsley, Luke Bedford, Lindsay J Coupland, Ian G Charles, Ngozi Elumogo, John Wain, Reenesh Prakash, Mark A Webber, SJ Louise Smith, Meera Chand, Samir Dervisevic, Justin O'Grady, The COVID-19 Genomics UK (COG-UK) consortium <h4>Summary:</h4> Between March and August 2020, over 3,200 COVID-19 cases were reported in Norfolk. 1565 positive clinical samples from 1376 cases were collected in four major hospitals, multiple minor hospitals, care facilities and community organisations within Norfolk and the surrounding area were collected and subjected to whole genome sequencing. 1035 cases resulted in genomes of sufficient quality for phylogenetic analysis, which revealed the presence of 26 distinct global lineages and 100 distinct UK lineages, with local evolution at a rate of 2 SNPs per month. Sequence data was combined with clinical metadata to understand the origin, genetic variation, transmission and spread of SARS-CoV-2 within the region. Highlights from this county-level analysis included the identification of a single sub-lineage associated with cases in 6 care facilities; confirming an outbreak at a food-processing facility; the ruling out of a nosocomial origin for another outbreak; and the identification of 16 lineages in health care workers not present in patients, demonstrating the effectiveness of infection control measures. The analysis also found that the D614G spike protein variant dominated in the samples, while longitudinal samples showed no evidence of reinfection. <hr /> <h3>Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK</h3> <em>BioRxiv</em> - doi: <a href="https://doi.org/10.1101/2020.09.23.309948" target="_blank" rel="noopener">https://doi.org/10.1101/2020.09.23.309948</a> <h4>Authors:</h4> Margaret J Hosie, Ilaria Epifano, Vanessa Herder, Richard J Orton, Andrew Stevenson, Natasha Johnson, Emma MacDonald, Dawn Dunbar, Michael McDonald, Fiona Howie, Bryn Tennant, Darcy Herrity, Ana Da Silva Filipe, Daniel G Streicker, Brian J Willett, Pablo R Murcia, Ruth F Jarrett, David L Robertson, William Weir, the COVID-19 Genomics UK (COG-UK) consortium <h4>Summary:</h4> During the COVID-19 pandemic, naturally occurring infections following transmission have been reported in domestic and non-domestic cats, dogs and mink. In this study, two cats from different COVID-19-infected households in the UK were shown to be infected with SARS-CoV-2 from humans. Infection was demonstrated using a range of approaches, including immunofluorescence, in situ hybridization, PCR testing. Post-mortem tissue samples for cat 1 displayed pathological and histological findings consistent with viral pneumonia, while cat 2 presented with rhinitis and conjunctivitis. Whole genome sequencing and analysis of the virus from cat 2 revealed five single nucleotide polymorphisms (SNPs) compared to the nearest sequenced UK human SARS-CoV-2 isolate (from the same UK county), although comparison with genomes from 9 other feline SARS-CoV-2 isolates revealed no shared cat-specific mutations. At present, there is no evidence of cat-to-human transmission or that cats, dogs or other domestic animals play any appreciable role in the epidemiology of human infections with SARS-CoV-2. <hr /> <h3>Download a PDF of this Report</h3> <ul> <li><strong><a href="https://www.cogconsortium.uk/wp-content/uploads/2020/10/15th-October-2020-Report-–-COVID-19-Genomics-UK-COG-UK-Consortium.pdf" target="_blank" rel="noopener">15th October 2020 Report – COVID-19 Genomics UK (COG-UK) Consortium.pdf</a></strong></li> </ul> [options_news_type] => Report [options_exclude_from_feeds] => 0 [ID] => 1161 [post_title] => Report 12: 15th October 2020 – COVID-19 Genomics UK (COG-UK) Consortium [post_type] => news_item [post_excerpt] => [post_content] => [post_url] => https://www.cogconsortium.uk/news_item/report-12-15th-october-2020/ [post_name] => report-12-15th-october-2020 [created_at] => 2020-10-16 09:38:49 [updated_at] => 2020-10-24 22:05:06 [large_image_url] => /wp-content/uploads/2020/10/report12_coguk-1024x391.jpg [main_image_url] => /wp-content/uploads/2020/10/report12_coguk-1024x391.jpg [main_image_caption] => [image_string] => src="/wp-content/uploads/2020/10/report12_coguk-1024x391.jpg" class="news-image" style="object-fit: cover" )
Report 12: 15th October 2020 – COVID-19 Genomics UK (COG-UK) Consortium
COG-UK genome sequence data and tools have been used in more than 120 retrospective and live public health outbreak investigations in the UK since March 2020. Analysis of COG-UK and GISAID data highlights the need to establish a systematic approach for monitoring the appearance and spread of all variants of the SARS-CoV-2 virus