Real-time tracking of RNA viruses using Nextstrain


Richard Neher
Biozentrum & SIB, University of Basel


slides at neherlab.org/202106_EPFL.html

by Trevor Bedford
by Trevor Bedford

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

Available data on Jan 26

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

Interactive part on Nextstrain

VoCs have more mutations than expected...

nextstrain

VoCs and VoIs: rapid converging evolution

covariants.org by Emma Hodcroft

VoCs have been replacing other strains quickly

S-gene positivity in the UK
Althaus et al, 2021, PHE Technical Briefing
  • How unusual is this?
  • How do we tell early on whether a variant is more transmissible?
  • How important are travel and seasons?

Recurrent mutations are common

  • RNA viruses are not mutation limited
  • In suitable environments, homoplasies are common
  • Clearly selected variation, but they don't necessarily sweep

Do A/H3N2 mutations have inertia?

Barrat-Charlaix et al, 2020

Fixation probability is quasi-neutral

A/H3N2 influenza
Simulations with increasing interference
Barrat-Charlaix et al, 2020

Diversity in immune responses

Lee et al, 2019

A/H3N2 influenza doesn't quite fit the textbook picture of rapid adaptation

  • Strong signal of positive selection
  • Evolutionary rate at antigenic sites very high
  • Rapid clade displacement, interference
  • Any given escape only allows to escape a fraction of the population
    → expiration of selection long before a mutation is common
  • The more diverse the immune landscape, the more neutral it looks

SARS-CoV-2 variants

CoVariants.org

SARS-CoV-2 variants can become dominant without advantage

Hodcroft et al

High case numbers in Spain and high travel volume spread the variant

Hodcroft et al

Travel driven variant dispersal and displacement

  • High invidence differential and high travel volume can shift variant distribution
  • Travel associated activities and behavior further increases impact
  • Onward spread in traveling demographics can be higher
  • We will see whether this also holds for 21A (delta)
  • Very easy to jump to premature conclusions

Travel driven variant dispersal and displacement

  • rapid rise to dominance
  • BUT: India had very high incidence
  • travel between UK-India was high in March/April (put on red list on April 23rd)
  • Likely hundreds of imports
  • The variant is diverse and dates back to last summer.

Transmission advantage relative to original variants likely.

But unclear how much.

Human corona viruses have pronounced seasonal prevalence (Sweden)

  • Respiratory virus incl seasonal CoVs show seasonality
  • Forcing through human behavior (indoor/outdoor activities).
  • Control of the virus might be harder in temperate winter
  • Absolute effect of seasonality unknown
Neher et al

Potential transition to an endemic seasonal virus (model from Feb 2020)

Influenza acknowledgements

  • Boris Shraiman
  • Trevor Bedford
  • Pierre Barrat
  • All the NICs and WHO CCs that provide influenza sequence data
  • The WHO CCs in London and Atlanta for providing titer data

SARS-CoV-2 acknowledgements

  • Emma Hodcroft (now in Bern)
  • Moira Zuber (Basel)
  • Iñaki Comas and Fernando Gonzalez-Candelas, Valencia
  • Martina Reichmuth and Christian Althaus (Bern)
  • Tanja Stadler, Sarah Nadeau, Tim Vaughan at ETH
  • Alberto Hernando and David Matteo at Kido Dynamics
  • Jesse Bloom, Katherine Crawford at Fred Hutch
  • David Veesler, Alex Walls, Davide Corti, John Bowen at UW

Acknowledgments

Trevor Bedford and his lab -- terrific collaboration since 2014

especially James Hadfield, Emma Hodcroft, Ivan Aksamentov, Moira Zuber, John Huddleston, and Tom Sibley

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

Data are shared and curated by GISAID