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Fitness, growth and transmissibility of SARS-CoV-2 genetic variants

Nature Reviews Genetics volume 24, pages 724–734 (2023)Cite this article

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Abstract

The massive scale of the global SARS-CoV-2 sequencing effort created new opportunities and challenges for understanding SARS-CoV-2 evolution. Rapid detection and assessment of new variants has become one of the principal objectives of genomic surveillance of SARS-CoV-2. Because of the pace and scale of sequencing, new strategies have been developed for characterizing fitness and transmissibility of emerging variants. In this Review, I discuss a wide range of approaches that have been rapidly developed in response to the public health threat posed by emerging variants, ranging from new applications of classic population genetics models to contemporary synthesis of epidemiological models and phylodynamic analysis. Many of these approaches can be adapted to other pathogens and will have increasing relevance as large-scale pathogen sequencing becomes a regular feature of many public health systems.

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Fig. 1: Growth of the Delta variant in the UK in the spring of 2021.
Fig. 2: Phylogenetic evidence for increased transmissibility of Delta in England in the spring of 2021.

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Acknowledgements

The author acknowledges support from the Wellcome Trust (220885/Z/20/Z) and the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb). The author further acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO).

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  1. Department of Infectious Disease Epidemiology, MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, UK

    Erik Volz

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Glossary

Ancestral state estimation

Inference of the attributes of a virus (such as genotype) or host species (such as geographical location) of a lineage that is not directly sampled and observed but that is ancestral to a sample of genomes.

Antigenicity

The capacity for binding of the virus with antibodies and other cell-mediated (B cell and T cell) products of the immune system.

Birth–death-sampling model

A mathematical model that relates the rate of transmission over time (births) and the rate of sampling to the times of common ancestry and sample dates as inferred from a random sample of virus genomes; this framework enables inference of epidemic reproduction numbers.

Coalescent models

Mathematical models for virus genealogies that explain how genetic diversity within a random sample of genomes is influenced by epidemic history; this framework enables inference of epidemic growth rates and size.

Darwinian fitness

In the context of pathogen variants, the concept of the ability of a variant relative to other variants to produce an infection within hosts and to transmit to new hosts, thus generating new infections with the given variant.

Effective reproduction number

(Rt). A dimensionless number that describes the average number of secondary infections resulting from a primary infection at a specified time or place, and encapsulating reduction in transmission due to, for example, accumulation of immunity in a host population, changing behaviour or virus variant characteristics.

Fixation

The point at which genomic diversity is lost owing to complete predominance of a particular variant.

Founder effects

Reductions in genetic diversity that accompany the colonization of a new susceptible population by a small randomly selected subset of viral variants from a larger set of infections in a geographically distinct donor population.

Genetic drift

Random fluctuation of pathogen variant frequencies resulting from stochastic transmission within a finite-size population that results in the gradual loss or fixation of pathogen variants in the population.

Logistic growth

Growth in frequency of a variant such that the log odds of sampling a variant increases linearly per generation or per unit time; such growth is characterized by an exponential phase and deceleration to a steady state.

Non-neutral evolution

Changes in genetic diversity of the virus due differences in fitness such as higher transmissibility or immune escape properties.

Proliferation

The spread and subsequent expansion of a novel virus variant to a new geographical region or risk group in which it was not previously circulating.

Selection coefficient

A summary statistic describing fitness of a variant, often quantified in terms of the rate (per unit time or generation) that a variant will grow or decline in relation to the rest of a population.

Transmissibility

A measure of how efficiently a pathogen is transmitted between hosts that can variously be quantified in terms of secondary attack rates, reproduction numbers or hazard rates; this may be time and context dependent as it depends on behaviour and immunity of the host population.

Variants

Genetically distinct circulating forms of a virus, which for SARS-CoV-2 are typically characterized by multiple co-occurring nucleotide substitutions that can potentially lead to measurable changes in transmissibility, severity of infection, effectiveness of vaccines and therapeutics, and effectiveness of diagnostics.

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Volz, E. Fitness, growth and transmissibility of SARS-CoV-2 genetic variants. Nat Rev Genet 24, 724–734 (2023). https://doi.org/10.1038/s41576-023-00610-z

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