Tuesday, December 08, 2020

CCDC Weekly: Models Suggest D614G Spike Protein Mutation Accelerates Transmission of COVID-19


 







#15,609

The SARS-CoV-2 virus which emerged in China in the last quarter of 2019, and subsequently embarked on a world tour in early 2020, has accrued a number of genetic changes as it traveled.  

While most of these mutations appear to offer no genetic advantage to the virus, one - D614G, which emerged in Europe - is believed to have improved COVID's transmissibility and replication rate, but doesn't appear to have impacted virulence.

By late spring this D614G strain was dominant in Europe, and gaining traction in North America, but China (and much of Asia) continued to deal with the original D614 strain (see map above).  

China, Japan, Taiwan, Hong Kong, Vietnam, and other Asian nations have managed to control their outbreaks far more successfully than Western nations, and while their quick COVID response and their public's compliance undoubtedly accounts for much of this, a less transmissible strain may have helped as well. 

China, which according to their official accounts continues report minimal COVID activity, attacks any community outbreak - no matter how small - with immediate shutdowns and mass testing.  

Additionally, Chinese officials have expressed grave concerns over any introduction of the supposedly more transmissible `European' strain of COVID into their country, as they fear it could prove much harder to control. 

One year ago this week, in CCDC Weekly: Vol 1 Number 1 - Plague In Inner Mongolia, we looked at the inaugural issue of China's equivalent of our CDC's MMWR.  It's format is quite similar, including a `Notes From The Field'  style report.

Over the past year we've looked at several of their reports on COVID, and today we have another which finds the R0 (pronounced R-naught) or Basic Reproductive Number of the European D614G strain to be substantially higher than the original Asian D614 strain.

The study's main conclusion (below) would seem to validate China's aggressive policy to prevent the D614G strain from gaining a foothold on the Mainland. 

Our findings demonstrated that the G614 mutation accelerated the transmission of the COVID-19 virus and also had higher spatial transmissibility, indicating that strains with G614, which were the dominant strains around the world, could spread on a larger scale and be more difficult to control. 

The full report (and PDF) can be read at the link below.

Epidemiological Model Suggests D614G Spike Protein Mutation Accelerates Transmission of COVID-19 — Worldwide, 2020
Liang Wang1; Yuhai Bi1,2, , ; George F. Gao1,2, , View author affiliations

Author Affiliations
1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China
2. University of Chinese Academy of Sciences, Beijing, China
Corresponding authors: Yuhai Bi, beeyh@im.ac.cn; George F. Gao, gaof@im.ac.cn
Online Date: November 26 2020
doi: 10.46234/ccdcw2020.247

 
The coronavirus disease 2019 (COVID-19) pandemic was caused by a novel type of coronavirus also known as SARS-CoV-2, 2019-nCoV, and HCoV-19 (1) and quickly spread around the world becoming a major threat to public health (2-3). Although COVID-19 virus is characterized as possessing a large genome and having limited genetic diversity (4) like other coronaviruses due to the high fidelity of its replication mechanism, many single nucleotide polymorphisms (SNPs) have been detected so far. Among the reported SNPs, the strain with the G614 mutation in the S protein has replaced the strain containing D614 as the world’s primary pandemic strain (5). However, it was still unclear if COVID-19 virus strains with G614 were more transmissible than those with D614 (6).

We reconstructed several transmission chains of COVID-19 during the early epidemic phase for 3 countries (Australia, the UK, and USA) based on genomic data from GISAID (7) and Bayesian inference under an epidemiological model for strains with D614 and G614 due to the similar amount of genomes within each country (Figure 1A). Then we inferred the R0 in those transmission chains to compare the difference of transmissibility among humans between D614 and G614 (see the Supplementary Material for details). 

The R0 caused by G614 was significantly higher than that caused by D614 in Australia and USA, as there was no intersection of 95% confidence intervals (CI) of the 2 distributions of R0 (Figure 1B). For the UK, the mean value of R0 for G614 was slightly higher than D614. For G614, its mean value of R0 was outside the 95% CI of the estimated R0 of D614. The mean value of R0 of D614 also was outside the 95% CI of the estimated R0 of G614. In addition, the R0 for D614 was similar among three countries (from 1.56 for USA to 1.73 for Australia). However, significantly different R0 was detected among countries (from 1.82 for the UK to 3.87 for USA), indicating that the spatial transmission of G614 had higher variation than D614.




Figure 1. The statistics and transmissibility of the COVID-19 virus with D614 and G614 during the early phases of the pandemic within each country.

(A) The number of publicly available genomes with D614 and G614 during the first two months after the first confirmed case in each country. The size of the pie chart is associated with the number of genomes. (B) The distribution of R0 for D614 and G614 during the first two months after the first confirmed case in each country. The mean of R0 is represented by a green point. The black line within the distribution represents the 95% confidence interval (CI).

Since the data used in this study were all collected during the early phases of each countries’ outbreak and no stringent prevention and control strategies were implemented in these three countries in those phases, the estimation of R0 would not be affected by non-pharmacological intervention. Thus, the result would better reflect the true nature of transmissibility within humans for strains with different mutations.
Our findings demonstrated that the G614 mutation accelerated the transmission of the COVID-19 virus and also had higher spatial transmissibility, indicating that strains with G614, which were the dominant strains around the world, could spread on a larger scale and be more difficult to control.
These results also echo those experimental results in vitro, in which both clinical samples and pseudoviruses with G614 have higher levels of viral RNA and titers compared to those with D614 (5).

As the COVID-19 pandemic spreads and continues, real-time monitoring and evaluation of the impacts of COVID-19 virus strain mutations need to be consistently maintained to provide earlier warnings for the public and provide evidence that supports government-led countermeasures and strategies.

Acknowledgments: We gratefully acknowledge the authors from the originating laboratories and the submitting laboratories where genetic sequence data were generated and shared via GISAID, enabling this research; Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB29010202, XDB29010102 and XDA19090118); National Science and Technology Major Project (Grant No. 2018ZX10733403, and 2018ZX10713001-010); National Natural Science Foundation of China (NSFC) (Grant No. 32041010 and 31900155); NSFC Outstanding Young Scholars (Grant No. 31822055); and Youth Innovation Promotion Association of CAS (Grant No. 2017122).
 
D614G isn't the only SARS-CoV-2 mutation on our radar.  

Five weeks ago, PrePrint: Emergence and Spread of a SARS-CoV-2 Variant Through Europe in the Summer of 2020, we looked at a recently emerged strain dubbed 20A.EU1, and since early November we've been tracking at least 7 mink variant COVID viruses which have emerged in Denmark (see WHO 2nd Update: SARS-CoV-2 mink-associated variant strain – Denmark).

It is pretty much inevitable that additional mutations will emerge, and while most will not substantially alter the impact or course of the pandemic, this study suggests that a tiny evolutionary tweak to the virus's S protein last winter may have made COVID far harder to control after it left Asia.