Thread by @trvrb

Omicron viruses can be divided into two major groups, referred to as PANGO lineages BA.1 and BA.2 or @nextstrain clades 21K and 21L. The vast majority of globally sequenced Omicron have been 21K (~630k) compared a small minority of 21L (~18k), but 21L is gaining ground. 1/15

Omicron clades 21K and 21L differ at ~40 amino acid sites, which is substantial in the context of SARS-CoV-2 evolution. 2/15

For comparison Alpha, Beta and Gamma are each about as divergent from each other in terms of amino acid changes across the genome as Omicron 21K and 21L are from each other. Figure from @nextstrain (nextstrain.org/ncov/gisaid/gl…). 3/15

The heavily mutated receptor binding domain (RBD) of the spike protein that distinguishes Omicron from Delta is largely shared between 21K and 21L, while differences exist in the near terminal domain (NTD). Figure from outbreak.info/compare-lineag…. 4/15

Given pattern of shared variation, I believe clades 21K and 21L may represent two spillover events from the same chronic infection (with rare lineage BA.3 representing a third spillover). 5/15

Whatever their origin, it appears that Omicron 21K got a head start on 21L and it represents the large majority or circulating Omicron viruses. However, 21L has become predominant in Denmark and India, and is spreading elsewhere. 6/15

Here, @marlinfiggins and I take case counts from @OurWorldInData and sequences from @GISAID to analyze clade-specific spread in terms of epidemic growth rate r, comparing Delta to Omicron 21K and 21L using methods discussed previously. 7/15

https://twitter.com/trvrb/status/1471651831923150848

We see that Omicron 21L is increasing in frequency in multiple countries with Denmark currently estimated at ~82%, the UK at ~9% and the US at ~8%. 8/15

This increase in frequency corresponds to exponential growth in terms of cases, where exponential growth is visible as a straight line increase on a log scale. 9/15

In each country and across time, we see that the epidemic growth rate of Omicron 21L is greater than Omicron 21K. Further plots available here: github.com/blab/rt-from-f…. 10/15

Given that Omicron 21K viruses spread easily in populations with prior immunity and given that @UKHSA reports similar VE for 21K and 21L (assets.publishing.service.gov.uk/government/upl…), I'd suspect that 21L's advantage derives from intrinsic transmission rather than greater immune escape. 11/15

The extensive wave of Omicron 21K in the US and elsewhere has created a large degree of immunity to Omicron 21K and very likely to 21L. 12/15

https://twitter.com/trvrb/status/1483996723458445319

Given differences in NTD between Omicron 21K and 21L, it may be possible to see some re-infections of individuals recovered from 21K by 21L. 13/15

But given that we'll still have ~60% of the US that weren't infected in the January Omicron 21K wave, this leaves the potential for a more transmissible Omicron virus to spread further in this fraction of the population. 14/15

This said, I would guess we'll see 21L create a substantially longer tail of circulation of Omicron than would have existed with just 21K, but that it won't drive the scale of epidemics we've experienced with Omicron in January. 15/15