Tuesday, May 05, 2020

More COVID-19 (SARS-CoV-2) Mutation Reports


Two weeks ago, in COVID-19 & The `M' Wordwe looked at the inevitability of seeing ongoing mutations in SARS-CoV-2 - the virus that causes COVID-19 - and our general lack of understanding of what most of those mutations would mean for the virus and its hosts (meaning us).
All viruses mutate, some very slowly, and others - like HIV or Influenza - very rapidly.  Most mutations convey no biological advantage to the virus, and many are actually detrimental.  Only a few are apt to `improve' the fitness of the virus. 
But, when viruses make trillions of copies of themselves, every once in awhile a more biologically `fit' virus will emerge.  One that can compete with its parental strain, and sometimes even supplant it.
Scarcely a day goes by without seeing a new (usually preprint) article or study, suggesting that SARS-CoV-2 has mutated in one way or another. 
While these `preprint' articles are a wonderful way to get an early look at the latest scientific research, evidence and thought, they have not been rigorously peer-reviewed. 

The latest report to make waves comes out of the Los Alamos National Laboratory, a research center which is known for their superb computer modeling prowess, that describes a new, now dominant `European' strain of COVID-19 which appears to have enhanced transmissibility. 

The full 33-page PDF file is available for downloading. I've only posted the abstract below. 

Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2
B Korber,  WM Fischer,   S Gnanakaran, H Yoon,   J Theiler, W Abfalterer,   B Foley, EE Giorgi,   T Bhattacharya, MD Parker, DG Partridge, CM Evans,  TI de Silva, on behalf of the Sheffield COVID-19 Genomics Group,  CC LaBranche, DC Montefiori
doi: https://doi.org/10.1101/2020.04.29.069054
This article is a preprint and has not been certified by peer review [what does this mean?].
Preview PDF
We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics.
To date we have identified fourteen mutations in Spike that are accumulating.
Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling.
The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.
          (Continue . . . )

For those not willing to wade through the full report, the Los Angeles Times has a lengthy report on this study (see link below). 
A mutant coronavirus has emerged, even more contagious than the original, study says
MAY 5, 2020
The gist of this report is a new strain (G clade) of SARS-CoV-2 emerged in Europe in February carrying the D614G mutation (among others), and has since overtaken the original Asian strain in many regions of the world due to its enhanced transmissibility.
This might explain why China was able to control - albeit with draconian measures - transmission of the original virus while European nations and the United States have been less successful in doing so with later iterations.  
It might also have ramifications for vaccine development, or even re-infection with the virus.  The operative word in both statements being `might'.  There is an awful lot here we still don't understand about how these mutations actually function.

But, this isn't the only study to find the D614G mutation (Clade G) spreading in Europe.  From researchers at the University of Bologna: Bologna, IT.
Geographic and Genomic Distribution of SARS-CoV-2 Mutations
Daniele Mercatelli   and Federico Manuel Giorgi
Version 1 : Received: 29 April 2020 / Approved: 30 April 2020 / Online: 30 April 2020 (11:15:17 CEST)

The novel respiratory disease COVID-19 has reached the status of worldwide pandemic and large efforts are currently being undertaken in molecularly characterizing the virus causing it, SARS-CoV-2. The genomic variability of SARS-CoV-2 specimens scattered across the globe can underly geographically specific etiological effects.
In the present study, we gather the 10,014 SARS-CoV-2 complete genomes currently available thanks to the collection endeavor of the GISAID consortium and thousands of contributing laboratories. We analyze and annotate all SARS-CoV-2 mutations compared with the reference Wuhan genome NC_045512.2. 
Our analysis shows the prevalence of single nucleotide transitions as the major mutational type across the world. There exist at least three clades characterized by geographic and genomic specificity. In particular, the clade G, prevalent in Europe, carries a D614G mutation in the Spike protein, which is responsible for the initial interaction of the virus with the host human cell. Our analysis may drive local modulation of antiviral strategies based on the molecular specificities of this novel virus.
Although they found a relatively low rate of mutation among the SARS-CoV-2 sequences examined, the virus has already evolved into 3 distinct clades, and more genetic diversity is inevitable. The authors write:
Our analysis confirms a low mutation rate of the virus, with an average of 6.7 mutations per sample with respect to the reference SARS-CoV-2 genome sequences. However, the existing mutations allow to group the samples into three distinct clades, G, S and V, characterized by a collection of specific mutations. The clades can be further characterized by most recent mutations and will likely be split even further in the future.
We'll need more research in order to understand the true meaning and impact of these, and future, mutations to the virus. SARS-CoV-2 sparked a pandemic because it successfully jumped species, and  figured out how to adapt to new hosts. 

Given that history, it would be overly optimistic to believe it will stop evolving now.