Estimating the transmission advantage of the D614G mutant strain of SARS-CoV-2, December 2019 to June 2020

Abstract

IntroductionThe SARS-CoV-2 lineages carrying the amino acid change D614G have become the dominant variants in the global COVID-19 pandemic. By June 2021, all the emerging variants of concern carried the D614G mutation. The rapid spread of the G614 mutant suggests that it may have a transmission advantage over the D614 wildtype.AimOur objective was to estimate the transmission advantage of D614G by integrating phylogenetic and epidemiological analysis.MethodsWe assume that the mutation D614G was the only site of interest which characterised the two cocirculating virus strains by June 2020, but their differential transmissibility might be attributable to a combination of D614G and other mutations. We define the fitness of G614 as the ratio of the basic reproduction number of the strain with G614 to the strain with D614 and applied an epidemiological framework for fitness inference to analyse SARS-CoV-2 surveillance and sequence data.ResultsUsing this framework, we estimated that the G614 mutant is 31% (95% credible interval: 28-34) more transmissible than the D614 wildtype. Therefore, interventions that were previously effective in containing or mitigating the D614 wildtype (e.g. in China, Vietnam and Thailand) may be less effective against the G614 mutant.ConclusionOur framework can be readily integrated into current SARS-CoV-2 surveillance to monitor the emergence and fitness of mutant strains such that pandemic surveillance, disease control and development of treatment and vaccines can be adjusted dynamically.

Keywords: COVID-19; D614G; SARS-CoV-2; fitness; mutation; phylogenetics; transmission advantage; variant of concern.

Figure 1

Weekly number of confirmed COVID-19 deaths and of SARS-CoV-2 sequences with D614 and G614, from phylogenetically defined transmission clusters, submitted by 10 included countries, February–June 2020

Figure 2

Global phylogeny of SARS-CoV-2, December 2019–June 2020 (n = 26,244)

Figure 3

Weekly proportion of SARS-CoV-2 sequences with G614 when both D614 and G614 strains cocirculated, 10 included countries, late January–mid-June 2020 (n = 10,915)

Figure 4

Estimates of SARS-CoV-2 G614 fitness under different phylogenetic definitions and minimum sizes of local transmission clusters, United Kingdom, late January–mid-June 2020 (n = 8,206)