Real-time tracking of virus evolution

Trevor Bedford (@trvrb)
Fred Hutchinson Cancer Center / Howard Hughes Medical Institute
5 Aug 2022
SURP Seminar
Fred Hutch
 
Slides at: bedford.io/talks

We work at the interface of virology, evolution and epidemiology

Segue through data vizualization

Data tells a story

Charles Minard and Napoleon's 1812 campaign

If data are looked at in the right way, answers become immediately clear

Edward Tufte

Above all, show the data

Barchart of average value

Box-and-whisker plot showing variation

Showing the data

To clarify add detail

Evolution of Conus shells

Greenland rising

Small multiples and dimensionality

Mapping infection spread

My research

Methods focus on sequencing to reconstruct pathogen spread

Epidemic process

Sample some individuals

Sequence and determine phylogeny

Sequence and determine phylogeny

Genomic epidemiology during the COVID-19 pandemic

Over 12M SARS-CoV-2 genomes shared to GISAID and evolution tracked in real-time at nextstrain.org

Richard Neher,   Emma Hodcroft,   James Hadfield,   Thomas Sibley,   John Huddleston,   Ivan Aksamentov,   Moira Zuber,   Jover Lee,   Cassia Wagner,   Denisse Sequeira,   Cornelius Roemer,   Victor Lin,   Jennifer Chang

Three key insights that genomic epi provided during pandemic

1. Rapid human-to-human spread in Wuhan beyond initial market outbreak
2. Extensive local transmission while testing was rare
3. Identification of variants of concern and mapping of increased transmission

Jan 11: First five genomes from Wuhan showed a novel SARS-like coronavirus

Jan 19: First 12 genomes from Wuhan and Bangkok showed lack of genetic diversity

Single introduction into the human population between Nov 15 and Dec 15 and subsequent rapid human-to-human spread

Rapid global epidemic spread from China

Epidemic in the USA was introduced from China in late Jan and from Europe during Feb

Direct introduction from China ~Feb 1 responsible for the majority of the epidemic

Mitigation efforts visible in virus genetic diversity

After initial wave, with mitigation
efforts and decreased travel,
regional clades emerge

Repeated emergence of variant of concern viruses

Genetic relationships of globally sampled SARS-CoV-2 to present

Rapid displacement of existing diversity by emerging variants

Rapid accumulation of spike mutations driving displacement

S1 evolution remarkably fast relative to seasonal influenza

BA.4 and BA.5 emerging from South Africa with spike mutations 452R and 486V

BA.5 is now dominant in the US (and most of the world)

Variant-specific epidemics shown by partitioning case counts by variant frequency

Variant-specific Rt decreasing as immunity accumulates

Similar dynamics seen in other countries

BA.2.75 emerging from India that possesses a number of spike mutations on top of BA.2

Frequency growth outpacing BA.5 in India

Inferred initial Rt ~1.9, but rapidly decreasing due to lack of growing case counts in India

Lab directions

• Outbreak investigations (mumps in Washington, Ebola in DRC, monkeypox, etc...)
• Genomic surveillance in King County and Washington State
• Phylodynamics methods development
• Evolutionary forecasting methods development
• Software infrastructure for Nextstrain and genomic epidemiology
• Other applications of evolutionary dynamics (within-host malaria and cancer evolution)

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