Estimating the transmission advantage of the D614G mutant strain of SARS-CoV-2, December 2019 to June 2020
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Abstract
The 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.
Aim
Our objective was to estimate the transmission advantage of D614G by integrating phylogenetic and epidemiological analysis.
Methods
We 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.
Results
Using 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.
Conclusion
Our 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.
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SciScore for 10.1101/2020.09.22.20199810: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources A phylogenetic tree was built from these global sequences with high sequencing coverages of the genomes, using maximum likelihood heuristic search and GTR+CAT nucleotide substitution model in FastTree v2.1.11 30. FastTreesuggested: (FastTree, RRID:SCR_015501)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, we only considered the …
SciScore for 10.1101/2020.09.22.20199810: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources A phylogenetic tree was built from these global sequences with high sequencing coverages of the genomes, using maximum likelihood heuristic search and GTR+CAT nucleotide substitution model in FastTree v2.1.11 30. FastTreesuggested: (FastTree, RRID:SCR_015501)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, we only considered the D614G mutation and simply categorized the sequences on GISAID by aligning the spike protein region that contains the locus. We did not consider mutations in other loci that might provide necessary genetic background for D614G and act synergistically to affect the fitness of G614. The mutant D614G was detected sporadically among local cases in mainland Chinese provinces Guangdong and Zhejiang after February, but no sustained circulation of G614 clusters had been detected in mainland China until the recent Xinfadi outbreak in Beijing in June. The biological mechanism of increased spread of G614 is still unclear. Second, we estimated the date of infection approximately by deconvoluting the time series of the dates of sampling for sequence data or the dates of reporting of confirmed cases or deaths. Given the relatively high fitness advantage of G614, the date of exposure or symptom onset should be used instead of the date of sampling to generate more accurate fitness estimates, if clinical data of patients could be linked with sequences available on GISAID. Third, our fitness estimation is only applicable when D614 and G614 strain cocirculates, and therefore cannot be used to monitor the fitness of a newly emerged mutant strain that has not yet spread in the community or has already dominated the community transmission. Fourth, our method compares the relative fitness of two strains. We did not consider the scenari...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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