BA.2.75 is rapidly picking up multiple beneficial spike mutations

BA.2.75, Coronavirus, Evolution, Health, Infection, Omicron, Research, Transmission
BA.2.75* could become dominant globally by the end of October.

A report out from today from two Github contributors gives new insights into the complex growth pattern of BA.2.75. It’s a very important report, so we are going to republish the entire thing below.

 

BA.2.75 is rapidly picking up multiple beneficial spike mutations

It increasingly looks like BA.2.75* may dominate even the fittest BA.5* lineages because it is picking up beneficial spike mutations at a faster rate. While the BA.2.75* founder virus itself could be less fit than the fittest BA.5* sublineages like BF.7* (BA.5.2.1 with S:R346T), BA.2.75 has rapidly picked up multiple beneficial spike mutations.

In particular subsets of the following S1 mutations have been picked up by various lineages that have arisen from the BA.2.75 polytomy:

  • S:R346T (defining mutation of BL.1=BA.2.75.1.1, one of 3 defining mutations of BA.2.75.2, very homoplasic, growth advantage: 4-8%/day)
  • S:R356T (defining mutation of BA.2.75.5, growth advantage: 5-10%/day)
  • S:F486S (one of 3 defining mutations of BA.2.75.2, appears homoplasically in BA.2.75.3, growth advantage: 5-10%/day)
  • S:D574V (defining mutation of BA.2.75.1, growth advantage: ~3-4%/day)

While the growth advantages of the above mutations on their own are roughly in line with growth advantages conferred in BA.4/5 sublineages, what makes BA.2.75* different from BA.4/5* is that BA.2.75* is picking up multiple beneficial spike together.

The evolution of BA.2.75* is convergent to BA.4/5 as BA.4/5 itself has S:F486V and has repeatedly picked up S:R346T. By analogy, there is thus some hope that the repertoire of beneficial mutations is more or less exhausted by the above mutations.

 

Sublineages of BA.2.75 to watch

The following sublineages of BA.2.75 deserve attention as they are the most obvious candidates to become dominant in the next few months (BA.2.75 has comparative fitness to BA.5*):

  • BA.2.75.2 (S:346T, S:F486S, S:D1199N): growth advantage over BA.2.75 (~10-15%/day)
  • BL.1 (S:D574V, S:R346T): growth advantage over BA.2.75 (~5-10%/day)
  • BA.2.75.3 (S:R356T): growth advantage over BA.2.75 (~5-10%/day)

A growth advantage of 10%/day means it takes ~6 weeks from 1% share to 50%, (5%/day -> ~3 months, 3% -> ~5 months), if the growth advantage of the above lineages hold up, BA.2.75* could become dominant globally (including Europe) by the end of October.

The figure below shows how BA.2.75* with at least two out of the 4 mutations mentioned in the first section is growing fast in comparison to all BA.2.75*, within 1 month from first observation, these lineages have grown to >10% of BA.2.75*:

 

Recommended tool to monitor the latest designated lineages

The volunteer Federico Gueli maintains a very helpful covSpectrum collection of recently designated lineages, including the candidates for dominance at: https://cov-spectrum.org/collections/24

It is suggested to sort the list descending by CI (low) to counter the bias of new lineages having inflated growth advantage estimates.

By default, the growth advantage is relative to all sequences – but the baseline can be changed to e.g. BA.5*, or BA.5* & S:346T.

The region can be chosen as desired, for example Europe, to focus on what happens locally.

Here is the table with worldwide data and baseline BA.5*

 

Spike mutations that seem to confer growth advantages to BA.5

Given that the variant surveillance community tries to designate all lineages with significant growth advantages, the defining mutations of recently designated lineages can be taken as a proxy for mutations that seem to confer growth advantages to BA.5. The following mutations show up repeatedly:

  • S:R346T (most prominently in BA.2.75.2, BL.1, BA.4.6, BF.7, BF.11, BE.1.2, BA.5.2.6)
  • S:R346S (most prominently in BA.4.7, BF.13)
  • S:444M (BA.5.2.7)
  • S:444T (BE.1.1.1, BA.5.6.2)
  • S:444R (BF.16)
  • S:450D (BA.5.5.1, BF.14)
  • S:1020S (BF.3.1, BF.5)

Currently, there does not seem to be much space for BA.4/5* to move beyond picking up S:346T or similar single mutations. This makes it more likely that BA.2.75 or another yet unknown sublineage of BA.2 will become dominant in the next few months.

Github: Variant report 2022-08-31

 

Many thanks to Cornelius Roemer and Richard Neher at Github for all their hard work in putting this report together!

 

 

Omicron BA.2.75 – a potential successor to BA.5

 

 

 

 

Image by Siggy Nowak from Pixabay