Evolution and spread of SARS-CoV-2


Richard Neher
Biozentrum, University of Basel


slides at neherlab.org/202006_KITP.html

Acknowledgements

Trevor Bedford and his lab -- terrific collaboration since 2014

James Hadfield, Emma Hodcroft and Tom Sibley have led the recent development

Data we analyze are contributed by scientists from all over the world

Data are shared and curated by GISAID

Data summarized by Ian MacKay
Data summarized by Ian MacKay
Data summarized by Ian MacKay
Data summarized by Ian MacKay
Data summarized by Ian MacKay

SARS-CoV-2 and its relatives

  • SARS-CoV-2 is in the same family as SARS-CoV-1, MERS and two seasonal coronavirus
  • The latter cause mild disease, the former severe
  • SARS-CoV-2 spreads more easily than SARS-CoV-1 or MERS
  • Relatives are found in many different animals
  • Closest known relative is a virus isolated from bats
    (RaTG13, approx 96% identical)

Tracking diversity and spread of SARS-CoV-2 in nextstrain

Virus genomes change rapidly through time

A/Brisbane/100/2014
GGATAATTCTATTAACCATGAAGACTATCATTGCTTT...

A/Brisbane/1000/2015
GGATAATTCTATTAACCATGAAGACTATTATTGCTTT...

A/Brisbane/1/2017
GGATAATTCTATTAACCATGAAGACTATCATTGCTTT...

... tens of thousands of sequences...

Genome sequences record the spread of pathogens

in SARS-CoV-2 a new mutation accumulates about every 2 weeks
images by Trevor Bedford

Available data on Jan 26

Early genomes differed by only a few mutations, suggesting very recent emergence
nextstrain.org/ncov/2020-01-26

Early lessons from SARS-CoV-2 genomes (mid Jan)

  • The outbreak originated from one source
    → not repeated zoonoses from a diverse reservoir.
  • The common ancestor of all samples was Nov - early Dec 2019.
  • Family clusters showed up as identical genomes (expected)
  • A second clade emerged that will continue to spread
→ the closest to "real-time" we have experienced so far...
Figure by James Hadfield/Emma Hodcroft

Available data on June 4

The virus has reached most places where humans live
nextstrain.org/ncov

Available data on June 4

Different clades (virus variants) dominate in different parts of the US
nextstrain.org/ncov

Available data on June 4

Data from New York suggests viral diversity
nextstrain.org/ncov

Available data on June 4

The outbreak in New York was likely seeded by introductions from Europe
nextstrain.org/ncov

Genomes reveal how the virus moves around the globe

Tracing the origins of samples from Iceland

SARS-CoV-2 is remarkably mixed geographically -- genomes connect outbreaks in different places
Gudbjartsson et al, nextstrain.org/ncov

Current take-home from SARS-CoV-2 genomes

  • SARS-CoV-2 was disseminated widely before travel restrictions
    → Border closures had little effect (maybe if earlier)
  • The virus typically spread locally before it was noticed
    (while testing focussed on people with travel history to hotspots)
  • Temporal resolution by mutation is about 4 weeks
    → too low to resolve direct transmissions or directionality
    → sufficient to connect outbreaks and identify clusters
  • Currently no solid evidence for mutations with functional significance
    see Sergei Pond's analysis of signals of positive selection

The history of nextstrain -- KITP in summer 2014

Nextstrain started at the KITP/superbugs14 program


Trevor Bedford, FHCRC Seattle

Fighting misinformation

Conspiracy theories and sensationalist research

WRONG:

LIKELY WRONG:

  • Prevalence is high, the mortality is low
    False positive rates are not accounted for correctly, unrepresentative study populations
  • Some strains are more severe than others
    confounders not accounted for
  • Some strains are adapted to different parts of the world
    confounders not accounted for
  • many more....

Colorful trees are easily misinterpreted...

Low genetic diversity combined with very biased sampling → no directionality can be inferred
nextstrain.org/ncov

Acknowledgements

Trevor Bedford and his lab -- terrific collaborations since 2014

James Hadfield, Emma Hodcroft, and Tom Sibley have led the recent development

People at the frontlines: health care staff and everybody else who keeps things going...

Data we analyze are contributed by scientists all over the world

Data are shared and curated by GISAID

Seasonal variation in infectivity

Original title mid February...

Published two weeks later...

Seasonal incidence of influenza viruses

Data by the US CDC

Seasonal incidence of enteroviruses

Pons-Salort et al

Potential seasonal drivers

  • humidity (e.g. dry air increases time before droplets fall down)
  • temperature
  • UV light
  • behavior (e.g. time spent indoors, ventilation, heating)

Exact nature of forcing not relevant for this talk...

2009 pandemic influenza -- UK

By Dave Farrance - wikipedia

1918 influenza --- UK

Taubenberger et al
by Trevor Bedford

Human corona viruses have pronounced seasonal prevalence (Sweden)

Neher et al

SIR model with seasonal forcing

$$\beta(t) = \beta_0\left(1+\epsilon\cos(2\pi (t-\theta))\right)$$
People import new infections at rate $\nu$
Neher et al

Strong seasonality can be generated through strong forcing or resonance

Yellow: good fit -- Blue: poor fit

Neher et al

Seasonal forcing and the SARS-CoV-2 pandemic

Counter-factual scenario without strong social distancing!

Seasonal forcing and the SARS-CoV-2 pandemic

Potential transition to an endemic seasonal virus