Tracking and predicting SARS-CoV-2 variants with Nextstrain


Richard Neher
Biozentrum & SIB, University of Basel


slides at neherlab.org/202107_CSHL.html

Available data on Jan 26 2020

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

Emergence and dominance of VoCs

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

Relative growth advantage depends on setting

Africa

Asia

Europe
North America

South America
  • Intrinsic transmission advantage
  • Immune evasion → more (mild) reinfections
  • Likely depends on seropositivity in the population
  • Dozens of other variants with comparably mutational signatures

How do we tell early on whether a variant is concerning?

How unusual are the patterns of convergent evolution?

SARS-CoV-2 variants can become dominant without transmission advantage

  • Large differences in incidence (Spain vs most of Europe in Summer 2020)
  • High travel volume during summer 2020
  • Demographics with more social contacts
Hodcroft et al

Convergent evolution is common in RNA viruses

Recent Influenza A/H3N2 example:

4-fold convergence at positions 142 and 193 of HA1

  • RNA viruses are not mutation limited
  • In suitable environments, homoplasies are common
  • Variation at homoplasic positions is often selected
    → but success depends on background

Mutational signatures

Number of amino acid changes in the S1 domain
Prominent deletions the spike NTD
Common convergent deletion in NSP6

Growth measures and experimental scores

Recent growth rate
RBD escape based on deep mutational scanning.
Allie Greaney (Jesse Bloom's lab)

Conclusion

  • Since late 2020, dominance of variants with abundant changes in Spike
  • Success due to a complex mix of epidemiological, immunological and viral factors → hard to predict
  • Regional variation in success -- alas VoC Delta is successful across the globe
  • We don't know how flexible SARS-CoV-2 is...
 Zhou et al, 2021

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