Thread by @C_Althaus

The mutational profile of Omicron suggests a potentially significant transmission advantage. But can we already say something about increased transmissibility or immune evasion? I'll give it a try. Warning: Preliminary and based on VERY limited data. 1/15

The observed rapid replacement of Delta by Omicron in the province of Gauteng in South Africa is suggestive of a transmission advantage. 2/15

Fitting a multinomial logistic regression model to the proportion of different variants in South Africa results in an estimated growth advantage of Omicron of 0.43 (95% CI: 0.15-0.72) per day compared to Delta. 3/15

.@TWenseleers obtained a similar estimate of 0.38 per day. There are lots of caveats: Targeted sequencing, stochastic effects in low incidence settings, and successive superspreading events could significantly bias these estimates. But let’s continue from here. 4/15

Assuming the same generation time, the transmission advantage could act at two levels: 1) increase in transmissibility, 2) immune evasion. We recently developed a mathematical framework to relate differences in growth rates to these properties. 5/15 doi.org/10.1101/2021.0…

A potential increase in transmissibility can be expressed as ρD/R_w, where X is the estimated growth advantage (0.43 per day), D the generation time (5.2 days), and R_w the effective reproduction of the previous variant (~ 0.8 in RSA during October). 6/15 ibz-shiny.ethz.ch/covid-19-re-in…

This would result in an increased transmissibility of 280% (95% CI: 98-468%). With Delta having an R_0 = 5-6 in the Northern Hemisphere during winter, the R_0 of Omicron would be around 10-30. Not impossible, but such a jump seems rather unlikely. 7/15

If the transmission advantage acted via immune evasion only, the level of immune evasion would be ρD(1-Ω)/(ΩR_w), with Ω being the proportion of the population that has fully protective immunity against infection with earlier variants. 8/15

South Africa records an excess mortality of 230k during the pandemic, which corresponds to 0.39% of the overall population (github.com/dkobak/excess-…). We earlier estimated the infection fatality ratio for the population of South Africa to be 0.35% (doi.org/10.1007/s10654…). 9/15

Hence, it is likely that almost everyone in South Africa has been infected with #SARSCoV2 and developed partial immunity against reinfection. In addition, 24% of the population have been fully vaccinated. 10/15

Thus, the proportion of the population that is fully protected (‘immune’) against infection and further transmission must be quite high. If we assume Ω = 75%, we get an immune evasion of 93% (95% CI: 32-100%), i.e., Omicron evades protective immunity in 93% of individuals. 11/15

For Ω = 90%, we obtain an immune evasion of 31% (95% CI: 11-52%) ‘only’. This clearly illustrates the current level of uncertainty about Omicron, and I want to emphasize again the preliminary character of these calculations. 12/15

Still, I do expect partial immune evasion to be the main driver of the observed dynamics, but increased transmissibility cannot be ruled out so far. 13/15

The developments in South Africa and observations from other countries during the coming days and weeks will allow us to shed more light on the properties of Omicron. 14/15

Finally, thanks for the amazing work from @Tuliodna, @houzhou, @rjlessells, and their colleagues in South Africa, @firefoxx66 from @ISPMBern at @unibern for covariants.org, @richardneher and @trvrb for @nextstrain, and the many others working around the clock. 15/15