The story so far: The World Health Organization (WHO) has flagged the emergence of a new variant of the SARS-CoV-2 virus — the XE recombinant. The WHO further added that the recombinant virus was detected in the U.K. on January 19 and over 600 sequences have been reported and confirmed since.
How are variants created?
SARS-CoV-2, the virus that causes COVID-19, is an RNA virus which evolves by accumulating genetic errors in its genome. These errors are produced when the virus infects a person and makes copies of itself inside the host’s cells.
These errors (otherwise called mutations) are therefore a by-product of replication of SARS-CoV-2 inside the cell and may be carried forward as the virus continues to infect people. When viruses having a specific set of errors or mutations infect a number of people, this forms a cluster of infections descending from a common parental virus genome and is known as a lineage or a variant of the virus.
How are the variants named?
The PANGO network, an open global consortium of researchers from across the world, provides a system for naming different lineages of SARS-CoV-2. These variants or lineages are widely followed by epidemiologists for tracking the evolution of SARS-CoV-2.
What is a recombinant variant?
Apart from the errors in the virus genome, another process through which a virus increases its genetic diversity is recombination. Recombination occurs when, in extremely rare situations, two different lineages of the virus co-infect the same cell in the host and exchange fragments of their individual genomes which generates a descendent variant having mutations that occurred in both the original lineages of the virus. Recombination of lineages happens in a variety of other viruses, including those that cause influenza, as well as other coronaviruses.
Such recombination events occur typically in situations where two or more lineages of SARS-CoV-2 may be co-circulating in a certain region during the same time period. This co-circulation of lineages provides an opportunity for recombination to occur between these two lineages of SARS-CoV-2.
How many recombinant viruses have been detected?
While recombination events are not frequently observed for the SARS-CoV-2 virus, multiple recombinant lineages have been designated during the pandemic. The recombinant lineages are annotated by PANGO with an ‘X’ followed by an alphabet which indicates the order of discovery. Some previously detected and designated lineages include XA, a recombinant of B.1.1.7 (Alpha) and B.1.177 detected in the U.K., lineage XB detected in the U.S., and lineage XC detected in Japan, which is a recombinant of B.1.1.7 (Alpha) and AY.29 sublineage of Delta.
Three new recombinant lineages of SARS-CoV-2 have been recently designated by the PANGO network and are being monitored — XD, XE, and XF.
Lineages XD and XF are a combination of lineages AY.4 (a sublineage of Delta) and BA.1 (Omicron), while lineage XE is a combination of Omicron lineages BA.1 and BA.2. Lineage XD, which has the Spike gene of Omicron inserted into a Delta genome, was first detected in France and Denmark. Lineage XF was detected in the U.K. early in January 2022 but has since not shown any significant transmission events in the country. Lineage XE, also first detected in the U.K., is a recombinant having fragments of lineage BA.1 with the majority of BA.2 genome.
Although currently present in a very low proportion of genomes in the U.K., early data from the country show evidence of community transmission of XF.
Are recombinant variants more deadly?
Although recombination has been detected in SARS-CoV-2, it has not yet impacted public health in a unique way. There is little evidence to suggest that recombinant lineages have a varied clinical outcome compared to the currently dominant Omicron variant, although preliminary data from the U.K. health security agency suggests a transmission advantage over the Omicron variant. It is certain at this point in time that more data will be needed to ascertain the impact of these lineages on the epidemiology of COVID-19.
What are the methods through which recombinants are identified?
Identifying and tracking recombinant lineages for SARS-CoV-2 is a challenging task. This would require specialised tools and the availability of primary (or raw) data for genome sequences as similar variant combinations could also arise from inadvertent errors in sequencing or analysis as well as contamination of sequencing experiments. A cluster of recombinant genomes can be designated a lineage name by the PANGO network if it can be confirmed that samples in the cluster have a common origin and descend from two individual lineages of SARS-CoV-2. Additionally, there should be at least 5 genomes in the public domain belonging to the cluster, indicating an ongoing transmission of the lineage. Furthermore, screening the sequencing data of these samples should show no signs of contamination and meet the definition of a recombinant.
What lies ahead?
Since recombinations are extremely rare occurrences, it is unclear how and why the viruses recombine. It is, therefore, important to track recombination of SARS-CoV-2 lineages because it may lead to the generation of a viral lineage that is better at infecting people or transmitting from host to host. Regardless of the consequences that recombination events may have on the evolution of the virus, monitoring circulating SARS-CoV-2 genomes for evidence of recombination will not only help gain a better understanding of the ongoing evolution of SARS-CoV-2 but will also be able to give one a heads up, if a more “concerning” variant of the virus were to emerge.
Bani Jolly is a researcher at the CSIR Institute of Genomics and Integrative Biology. All opinions expressed are personal
