Explained | XBB.1.16, the Omicron recombinant behind India’s new COVID spike

Over the past three years and multiple waves of infection, SARS-CoV-2 continues to evolve by accumulating genetic variations. Uncommonly, a co-infection of multiple lineages of the virus could result in recombinations between genomes which can give rise to chimeric genomes, otherwise called recombinants.

While most recombinations may not give rise to viable viruses, there is a rare possibility that recombination could result in the creation of a new lineage of the virus with better functional capabilities than either of the parent lineages. Genome sequencing and surveillance of viruses could efficiently identify such recombinants, as they would have the variant complement of two-parent lineages.

Several recombinant lineages of SARS-CoV-2 have emerged during the course of the COVID-19 pandemic. The PANGO network, an international consortium of researchers for naming SARS-CoV-2 lineages, has an established system for identifying and designating recombinants of SARS-CoV-2. Currently, close to 100 recombinant lineages have been designated by the PANGO network, all of which begin with the letter ‘X’, followed by a letter to denote the order of their detection. 

Two recombinant lineages of SARS-CoV-2 are currently designated as ‘Variants Under Monitoring’ by the World Health Organization: XBB, a recombinant of Omicron sublineages BA.2.10.1 and BA.2.75, and XBF, a recombinant of BA.5.2.3 and BA.2.75.3 Omicron sublineages.

The lineage XBB.1.5, a sublineage of the XBB first identified in New York City in October 2022, is currently designated as a Variant of Interest (VOI) by the WHO. Tracking Omicron recombinants is important for the early detection of lineages that may have functional advantages over currently circulating variants such as increased transmissibility in populations with prior immunity to the virus. 

What is the XBB.1.16 lineage of SARS-CoV-2?

First detected in SARS-CoV-2 sequences from India, the XBB.1.16 is a recombinant lineage of the virus and is a descendent of the XBB lineage. The earliest sequence of this lineage belongs to a viral genome isolated in New York in January 2023 and the lineage has been seen to be circulating predominantly in India.

A significant number of the genomes from outside India, such as in the U.S. and Singapore, have been linked to international travel, mostly from India. The variant has to date been detected in at least 14 countries across the world. 

The lineage XBB.1.16 has a number of mutations in common with the VOI XBB.1.5. Additional key mutations including E180V and T478R in the Spike protein and I5T in ORF9b are present in the XBB.1.16 lineage.

In contrast, the XBB.1.5 has the mutation T478K in the Spike area. T478R is associated with immune escape, or the ability of the virus to evade antibodies raised from previous infections or vaccines. The ORF9b I5T mutation is also found in the lineage XBB.1.9 and has been widely believed to lend a growth advantage to the virus.

Preliminary data also suggest that XBB.1.16 has a higher growth advantage over currently circulating SARS-CoV-2 lineages, including the XBB.1.5 lineage.

Why is XBB.1.16 causing concerns in India?

Amid the ongoing increase in the number of seasonal Influenza H3N2 cases, an uptick in COVID-19 cases is being seen in India in March 2023, despite the low number of tests, as the total number of active COVID-19 cases across the country increased to over 6,000.

The fast-spreading XBB.1.16 lineage is believed to be responsible for the recent spike in COVID-19 cases in India. 

Although data from systematic genomic surveillance in India is limited, XBB.1.16 today accounts for more than 30% of all the sequenced genomes in March 2023, and its proportion has been seen to be increasing in the past few weeks, to become the major lineage in some states.

To date, the lineage has been found in samples from Telangana, Maharashtra, Karnataka, Gujarat, Delhi, Puducherry, Haryana, Himachal Pradesh, and Odisha. The states of Telangana, Karnataka, Gujarat and Maharashtra have reported the highest number of XBB.1.16 cases, but with the caveat that this could be biased as not all states proactively sequence samples.

The earliest genomes of XBB.1.16 available from India and deposited in GISAID, a global database for pathogen sequences, were from early February 2023, from Karnataka and Maharashtra.

Based on preliminary data, there is no evidence to suggest that infections with the XBB.1.16 lineage differ in clinical severity from those caused by other Omicron lineages, although the higher growth advantage also possibly the higher immune escape could lead to a higher risk of reinfection with XBB.1.16 compared to other circulating Omicron lineages.

Protecting the vulnerable through time-tested means could therefore significantly blunt the rise in infections. It will therefore be crucial to monitor the prevalence of XBB.1.16 and the clinical correlates in the coming days if cases continue to increase.

In summary

Genomic surveillance of SARS-CoV-2 has time and again proven to be essential for the early detection and tracking of new viral lineages including recombinants. Although vaccination and hybrid immunity against the disease remain effective in protecting against severe COVID-19 symptoms, further research is necessary to determine the impact of newly evolving lineages on how the pandemic progresses. 

As people continue to get infected and new lineages of the virus continue to emerge, time-tested preventive measures such as wearing masks and getting vaccinated, if you have not received the scheduled doses are more important than ever, since the COVID-19 pandemic is far from over.  

Bani Jolly and Vinod Scaria are researchers at the CSIRs Institute of Genomics and Integrative Biology in Delhi. All opinions expressed are personal.

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