March 4, 2020

expert reaction to study looking at whether there are two strains of the novel coronavirus

Research, published in National Science Review, reports on whether there are two strains of the novel coronavirus.

Dr Michael Skinner, Reader in Virology, Imperial College London, said:

“The study looks at evolution of SARS-COV-2 from Bat Nov TG13 (its closest ancestor) by looking at distribution primarily of mutations that don’t affect the protein going sequence (they’re “synonymous”) so don’t really affect how it behaves.  They show that SARS-COV-2 and TG13 are surprisingly distant, suggesting that they’re separated not only by the acquisition of ACE-2 receptor binding sequences in S1 (as previously noted by others) but by subsequent mutation and selection (i.e. evolution) over several decades.

“Sequencing of 100 SARS-COV-2 genomes from China and beyond, they identified two subtypes, differentiated by nucleotide substitutions at 8,782 (orf1ab: T8517C, synonymous) and 28,144 (ORF8: C251T, non-synonymous – S84L).  They label these S & L representing the amino acid encoded at ORF8 amino acid 84.

“They show that S is ancestral, being the form found in the closely related viruses like TG13. They also show that L became the most prevalent, especially in Wuhan, less so in the rest of China.

“The authors reasonably construct some tentative hypotheses which can now usefully be tested as we gather more sequences elsewhere.

“They speculate that the L form might be more “aggressive” but that is not an adjective we normally apply to viruses, where we talk about transmissibility, fitness, virulence.

“Viruses have to be able to replicate in each sequential host and transmit serially between them.  It is quite possible for one form of the virus to be better at replication, another at transmission.

“There can be selection of a particular form due solely to a “founder effect” – caused by infection with a single particle representing just one type of several possible.

“Molecular epidemiologists will be keen to see whether there has been preferential seeding of either form in the various affected countries outside of China, and whether either form predominates in the subsequent ongoing spread from the early foci of infection.

“It is, however, too early to speculate on any practical consequences of the interesting observation – though at the moment there’s no sign that it will affect vaccination strategies, as (unless I’m mistaken) the mutations don’t seem to have affected the sequence of the S1 spike protein which is the antigen most people are targeting for vaccine production.”

Dr Stephen Griffin, Associate Professor Section of Infection & Immunity, University of Leeds, said:

“What they seem to be saying is that after SARS-CoV2 first crossed into humans, the ancestral strain (S) subsequently evolved into another lineage (L).  Both of these are now apparently circulating.  The newer lineage was initially more prevalent, but is now reducing – the authors speculate that this lineage was more affected by human intervention as a result of it being better at spreading/more pathogenic.  The older (S) lineage appear less affected by preventative measures, due, say the authors to it being less virulent and so producing a lower level of more stable infections.

“It’s difficult to confirm studies like this without a direct side by side comparison of pathogenicity/spread in, ideally, an animal model, or at least a greatly extended epidemiological study.  The authors themselves admit that their sequencing data regarding the rise/fall of the second lineage is relatively scarce and recommend further investigations.

“It is usually the case that when RNA viruses first cross species barriers into humans they aren’t particularly well adapted to their new host (us!).  Thus, they usually undergo some changes allowing them to adapt and become better able to replicate within, and spread from human to human.  However, as this study hasn’t tested the relative “fitness” of these viruses when they replicate in human cells or an animal model, it isn’t really possible to say whether this is what’s happened to SARS-CoV2.  It is also difficult to say how/why human interference may have impacted upon one strain relative to the other for similar reasons.

“As such, I’m not sure that you can reasonably say yet whether this variability is linked to viral decline, or could be used to tell whether someone is likely to succumb to the virus – this second question is almost certainly due to a balance between the virulence of the virus, host genetics, age, underlying conditions, immune status and environmental factors.”

‘On the origin and continuing evolution of SARS-CoV-2’ by Xiaolu Tang et al. was published in National Science Review: https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa036/5775463

All our previous output on this subject can be seen at this weblink:

http://www.sciencemediacentre.org/tag/covid-19

The SMC also produced a Factsheet on COVID-19 which is available here:

https://www.sciencemediacentre.org/smc-novel-coronavirus-factsheet/

Declared interests

None received.