Continuing SARS-CoV-2 evolution and diversification post-Omicron
Trevor Bedford (@trvrb)
Fred Hutchinson Cancer Center / Howard Hughes Medical Institute
23 May 2022
Science for Resilience - Learnings from the Pandemic
Institute for Advanced Studies
Slides at: bedford.io/talks
1. SARS-CoV-2 evolution over the course of the pandemic
2. Omicron emergence and spread
3. Emerging variants
4. Expectations for endemicity
SARS-CoV-2 evolution over the course of the pandemic
Genetic relationships of SARS-CoV-2
Global SARS-CoV-2 evolution over the course of the pandemic
Rapid accumulation of spike mutations driving displacement
S1 evolved at a rate of 11 amino acid changes per year in 2021
S1 evolution remarkably fast relative to seasonal influenza
Omicron emergence and spread
Omicron viruses possess huge excess of mutations in S1
Omicron spike mutations substantially drop VE against infection
Significant immune escape drove large-scale epidemics
Starting Rt approached that of the initial wave in spring 2020
Omicron attack rate
- We estimate US has seen 9.8% of the population as confirmed cases of Omicron through Mar 3, with the large majority accumulating after Dec 15
- Assuming a case detection rate of 1 in 5 infections, we estimate almost 50% of the US infected with Omicron, most in the span of ~10 weeks
Similar epidemics across US states with downturn driven by immunity
Emerging variants
Initial variants characterized by repeated evolution at spike 484K and 501Y
We're now seeing repeated evolution at spike 452
This pattern is familiar from seasonal influenza
BA.4 and BA.5 emerging from South Africa with spike mutations 452R and 486V
BA.2.12.1 emerging from Northeastern US bearing spike mutation 452Q
Variant-specific epidemics shown by partitioning case counts with variant frequency
BA.4, BA.5, BA.2.12.1 driving cases across countries
Rt for BA.2.12.1 greater than BA.2 and Rt for BA.4/5 greater still
BA.4 and BA.5 driving substantial epidemics in South Africa
Expectations for endemicity
Immunity and reduced intrinsic severity has dropped CFR
Broad expectations of endemicity based on comparison with flu
- R0 of Delta/Omicron is perhaps ~6 compared to R0 of flu of ~2. At same rates of evolution and waning expect more COVID circulation.
- Before Omicron rates of evolution in SARS-CoV-2 S1 had been roughly equal to H3N2 flu. Omicron equivalent to 5 years of H3N2 evolution.
- Infection fatality rate (IFR) of COVID is roughly comparable to flu once you have prior immunity.
1, 2 and 3 suggest a virus that circulates at higher levels than flu, but individual infections aren't much more severe in terms of mortality than H3N2 influenza.
Seasonality suggests winter "COVID season", but Omicron-like events could overcome seasonality.
Key parameters are seasonal attack rate and IFR
- Assume seasonal attack rate of 40%, with Omicron-like emergence driving 80% some years.
- Assume IFR of 0.05% (compared to early pandemic IFR of 0.5%), but new variant could push this higher.
- This would give somewhere around 20 per 100k population yearly deaths at endemicity, but potential for variant emergence to push this over 40 per 100k population.
Acknowledgements
SARS-CoV-2 genomic epi: Data producers from all over the world, GISAID and the Nextstrain team
Bedford Lab:
John Huddleston,
James Hadfield,
Katie Kistler,
Louise Moncla,
Maya Lewinsohn,
Thomas Sibley,
Jover Lee,
Cassia Wagner,
Miguel Paredes,
Nicola Müller,
Marlin Figgins,
Denisse Sequeira,
Victor Lin,
Jennifer Chang
