02 September 2021
The World Health Organisation has recently assigned a new variant of Interest - Mu (B.1.621 and B.1.621.1) and has been widely discussed across the board. Public Health England had earlier assigned this as a variant under investigation, designated VUI-21JUL-01
The World Health Organisation designation of a Variant of Interest suggests that the designated variant has genetic changes which are predicted or known to affect characteristics including immune escape, transmissibility , disease severity and also has been suggested to cause significant community transmission or clusters in multiple counties, increasing relative prevalence along with cases and apparent epidemiological links to suggest an emerging risk. With further escalation, variants are designated as a Variant of Concern (VoC). Currently there are four Variants of Concern designated by the World Health Organisation - Alpha, Beta, Gamma, Delta and five variants designated as of Interest - Eta, Iota, kappa, Lambda and now Mu.
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The lineage is characterized by nine spike mutations, many of which have overlaps with other variants of concern. This includes spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H and D950N, These includes mutations previously well characterized to be independently associated with immune (antibody) escape including E484K, (also seen in Beta) as well as P681H (also seen in alpha) as well as R346K. ESC, a comprehensive database maintained at the CSIR Institute of Genomics and Integrative Biology systematically collects evidence of immune escape mutations in SARS-CoV-2 from published literature and resources lists these mutations and evidence on their immune escape properties. Some of the sequences of Mu variant in the United Kingdom also has the K417N mutations which are also shared by the AY.1 and AY.2 sub lineages of delta (also popularly known as delta+) . The constellation of mutations prompted the World Health Organisation to keep the variant in the watchlist since these mutations have been independently associated with immune escape and also shared by other variants of concern.
The World Health Organisation has recently assigned a new variant of Interest - Mu (B.1.621 and B.1.621.1) and has been widely discussed across the board. Public Health England had earlier assigned this as a variant under investigation, designated VUI-21JUL-01
The World Health Organisation designation of a Variant of Interest suggests that the designated variant has genetic changes which are predicted or known to affect characteristics including immune escape, transmissibility , disease severity and also has been suggested to cause significant community transmission or clusters in multiple counties, increasing relative prevalence along with cases and apparent epidemiological links to suggest an emerging risk. With further escalation, variants are designated as a Variant of Concern (VoC). Currently there are four Variants of Concern designated by the World Health Organisation - Alpha, Beta, Gamma, Delta and five variants designated as of Interest - Eta, Iota, kappa, Lambda and now Mu.
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| The mutation spectrum of Spike protein across the major variants of interest. (Source outbreak.info) |
The lineage is characterized by nine spike mutations, many of which have overlaps with other variants of concern. This includes spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H and D950N, These includes mutations previously well characterized to be independently associated with immune (antibody) escape including E484K, (also seen in Beta) as well as P681H (also seen in alpha) as well as R346K. ESC, a comprehensive database maintained at the CSIR Institute of Genomics and Integrative Biology systematically collects evidence of immune escape mutations in SARS-CoV-2 from published literature and resources lists these mutations and evidence on their immune escape properties. Some of the sequences of Mu variant in the United Kingdom also has the K417N mutations which are also shared by the AY.1 and AY.2 sub lineages of delta (also popularly known as delta+) . The constellation of mutations prompted the World Health Organisation to keep the variant in the watchlist since these mutations have been independently associated with immune escape and also shared by other variants of concern.
The initial genome of this variant was identified in January this year from South America and presently this variant was found in at least 32 countries across the world. The largest proportions of the lineage are found in Colombia, Dominican Republic and Ecuador. The lineage forms the majority lineage in Colombia. Efficient transmission was observed in comparison with Alpha early this year, though there is no evidence to suggest that the variant outcompetes delta in the recent weeks in Colombia.
The early interest in July this year came from reports from the Public Health England which suggested reduction in neutralisation by vaccinee sera in pesudovirus assays and suggests the immune escape properties of the variant is similar to Beta. A sub-lineage B.1.621.1 has also been designated, the first sequence of this sublineage from April this year.
While the prevalence has been high in South American countries like Colombia and Ecuador, the global prevalence of the variant has been less than 1% in July-August and has seen a consistent decline in numbers. The total number of cases in these countries have also been showing a decline in the recent weeks. Beyond South America, the variant has also been observed in the United States of America, European countries including Spain, Italy, Netherlands and Portugal.
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| Estimated prevalence of the Mu variant of interest (Source outbreak.info Accessed 02/09/2021) |
While there is emerging evidence to support the immune escape properties of the variant, no evidence suggests that the variant is more transmissible or has been outcompeting Delta in any geographies. With delta gaining ground in many regions, and with no evidence suggesting that the variant can outcompete delta, it is unlikely that the variant would be of concern anytime soon.
The Indian SARS-CoV-2 Genome surveillance dashboard maintained at the CSIR Institute of Genomics and Integrative Biology which currently reports over 60,000 SARS-COV-2 genomes sequenced as part of INSACOG as well as other state surveillance programmes does not suggest any occurrence of B.1.621 in India yet.
While no country is likely to be spared of emerging variants, in the era of globalisation, one should always keep in mind that variants come up as a function of the ongoing SARS-CoV-2 infections across the globe. With a significant disparity in availability of vaccines and the proportions of people vaccinated against SARS-CoV-2 across the globe, this calls for urgent efforts to ensure there is a rapid and equitable deployment of vaccines and to understand and counter growing vaccine hesitancy in some parts of the world.
References
Indian COVID-19 Genome Surveillance Dashboard at the CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) https://clingen.igib.res.in/covid19genomes/ Accessed 02/09/2021
Tracking SARS-CoV-2 Variants https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ Accessed 02/09/2021
Outbreak.Info http://outbreak.info Accessed 02/09/2021
Comprehensive Resource of Immune Escape Variants in SARS-CoV-2 maintained at the CSIR Institute of Genomics & Integrative Biology (CSIR-IGIB) http://clingen.igib.res.in/esc/
About the Author
Vinod Scaria is a scientist at the CSIR Institute of Genomics and Integrative Biology and can be reached at @vinodscaria on Twitter
All opinions expressed are personal and do not reflect the opinion of their employers or organizations associated.
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