2 Sep 2021

Explainer: Generation and transmission of inter-lineage recombinants in the SARS-CoV-2 pandemic

For the first time, COG-UK researchers have reported the clear detection and characterisation of recombinant SARS-CoV-2 viruses — both their generation and subsequent transmission within the community.

The study, recently published in Cell and led by researchers at the University of Edinburgh, found evidence for multiple independent recombination events of viruses sampled from late 2020 to early 2021 in the UK.

These recombinant viruses carry many of the single nucleotide polymorphisms (substitution of a single nucleotide at a specific position in the genome) and deletions (mutation involving the loss of genetic material) that are characteristic of the B.1.1.7 variant of concern, now known as Alpha. However, part of these viruses’ genomes also share genetic variation identical to SARS-CoV-2 variants other than Alpha that were simultaneously circulating in the same geographic area.

Researchers identified 16 recombinant genome sequences within the COG-UK dataset, and found evidence for four instances of onward transmission of a recombinant virus, including one lineage which circulated for at least nine weeks and resulted in a cluster of 45 associated COVID-19 infections (termed lineage ‘XA’ by the Pango nomenclature).

Why are we interested in monitoring recombinant SARS-CoV-2?

Recombination is the transfer of genetic material between different regions of a genome, or between the genomes of different organisms. While recombination is a fundamental evolutionary process because it drives genetic variation, in the context of virus evolution, it has the potential to instigate a worrying scenario.

The process of recombination can offer the opportunity to unite genetic variation from different viruses onto a single genome. So in theory, this could result in the combination of advantageous mutations — for instance, those that enable immune-escape (helping the virus to slip past the body’s immune defences), with those that enhance transmissibility of SARS-CoV-2. A recombinant virus with both of these properties would pose a serious risk, thus demonstrating why monitoring recombination in SARS-CoV-2 is vital.

When is recombination likely?

Recombination between genetically-distinct viruses can only occur when a person is simultaneously co-infected with both ‘parental’ viral variants, and is therefore most likely to arise when COVID-19 case numbers are high within a population. From mid-October 2020 to January 2021 in the UK, while virus prevalence was already high, Alpha rapidly emerged and spread across the nation, leading to co-circulation of Alpha and other SARS-CoV-2 variants. This created an environment conducive to recombination between genetically-distinct SARS-CoV-2 viruses.

Should we be concerned about the recombinant ‘XA’ cluster?

Researchers found that the cluster acquired Alpha’s set of spike mutations (which likely contribute to Alpha’s enhanced transmissibility), but had no clear biological advantage besides this. However, the findings support the need for continued surveillance of new variants and recombinant lineages, particularly as the co-circulation of Variants of Concern and genetic diversity of SARS-CoV-2 continues to increase globally over the course of the pandemic. But ultimately, reducing the prevalence of SARS-CoV-2 will minimise the chance that recombinant viruses with advantageous mutations will form.

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.