Thread by @trvrb

I think there's perhaps been some confusion regarding transmissibility vs immune escape in Omicron. The apparent rapid increase in frequency of Omicron in Gauteng does not mean that Omicron is necessarily more intrinsically transmissible than Delta. 1/15

This diagram shows estimated increase in intrinsic transmissibility from work by @marlinfiggins (

https://twitter.com/trvrb/status/1447566579646930944

) along with fold drop in neutralization titer compiled from Uriu et al (biorxiv.org/content/10.110…) and similar papers. 2/15

We see that previous variants have showed only modest potential for escape from immunity engendered by vaccination or infection with circulating SARS-CoV-2 viruses, but have varied considerably in their intrinsic transmissibility with Delta outpacing others. 3/15

These variants have generally had 8-10 mutations in the S1 domain of spike protein, while Omicron has perhaps 25 or 30. Extremely rough, but I'd guess that this could translate into something like a 20 (or perhaps 30)-fold drop in titer. 4/15

https://twitter.com/trvrb/status/1464353245380243457

However, given that Omicron lacks so many of the non-spike mutations that have seemed to contribute to Delta's increased fitness (medrxiv.org/content/10.110…), I wouldn't be surprised if its intrinsic transmissibility is similar to Gamma, etc... as shown here. 5/15

I'd like to emphasize that the above placement of Omicron is guesswork at the moment and should be taken as such. Here, my main purpose is to illustrate how immune escape plays out in terms of transmission rate. 6/15

Person-to-person transmission potential can be quantified with Rt as the number of secondary infections caused by an index case by a particular variant in a particular context and depends on both intrinsic transmissibility and immune escape. 7/15

However, given high levels of population immunity to the original strain, partial immune escape can cause more rapid spread than increased intrinsic transmissibility. 8/15

This plots Rt as a function of intrinsic transmissibility and immune escape. With high levels of population immunity, a hypothetical Omicron virus with modest R0 but partial immune escape will spread faster than a Delta-like virus with high R0 but little immune escape. 9/15

This concept is explained with more mathematical rigor by @C_Althaus, where he infers a potentially sizable level of immune escape based on observed rate of displacement of Delta by Omicron in South Africa. 10/15

https://twitter.com/C_Althaus/status/1464922715865948160

Note that these estimates of current fitness advantage of Omicron are very likely to get lower in the coming days as bias from preferential sequencing eases as more surveillance samples are sequenced. 11/15

https://twitter.com/trvrb/status/1464353251147481089

Critically, even if Omicron has a significant immune escape phenotype, infection by Omicron should elicit Omicron-specific immunity. It's not like antibiotics where the bacteria becomes broadly resistant. 12/15

Instead, the virus can change its shape and escape from existing antibodies, but this new shape can still be targeted by antibodies from infection or vaccination (with an updated formulation). 13/15

Additionally, it's possible for Omicron to show significant immune escape from infection resulting in rapid spread but that immunity to severe outcomes remains more robust (the same dichotomy we saw with waning immunity). 14/15

We'll see as this unfolds, but I expect contributions of intrinsic transmissibility vs immune evasion to be distinguished via:
1. neutralization assays
2. variant-specific vaccine effectiveness
3. modeling approaches along the lines of those above by @C_Althaus
15/15