There is one, and only one strain of SARS-CoV-2

coronavirusThe moment a preprint emerges describing a new patient isolate of SARS-CoV-2, with a change in the genome sequence, the world seems to explode with concern about a new viral ‘strain’. I want to explain why such angst is misguided and in the process explain exactly what is a virus strain and a virus isolate.

In science, word usage matters. And sadly, even virologists often do not use their terms properly. I’ve written about it before.

When SARS-CoV-2 is isolated from a COVID-19 patient, that virus is called an isolate. The origin of the term is clear: the virus has been isolated from a patient.

These virus isolates are all the same strain of SARS-CoV-2. They are not different strains, even if they have changes in their genome sequences. A virus strain is an isolate with a different biological property, such as binding to a different receptor, or having a distinctly different stability at higher temperatures, to give just two of many possible examples.

There is only one strain of SARS-CoV-2. The first virus isolate, taken from a Wuhan patient in December 2019, is the same strain as the most recent isolate taken anywhere else in the world in May 2020. So far no one has shown that any of these virus isolates differ in any fundamental property.

I can hear some of you shouting, but isn’t a nucleotide change enough to make a strain? The answer is a resounding NO. Every virus expelled by an infected individual differs from the next by many base changes. It would be foolish and of little utility to call each patient isolate a strain. That term is reserved only for special changes that confer a new property to the virus.

No doubt you have heard reports of different SARS-CoV-2 strains, but I assure you they are likely wrong. Some time ago it was claimed in China that there were ‘L’ and ’S’ strains with distinct pathogenicity in humans. Wrong. You will also hear that there are eight circulating strains of the virus. Wrong. These are all isolates. None have been shown to have a distinct biological property, no matter what the preprints claim.

Most of these claims are in preprints and, if the scientific review process does its job, most of them will simply be reports of new genome sequences with no associated biological changes.

The most recent offender is a preprint claiming that SARS-CoV-2 with an amino acid change in the spike glycoprotein (D614G) increases the transmissibility of the virus. The claim that this amino acid change increases viral transmission is unsubstantiated and likely incorrect. There is no doubt that viruses with the D614G change are emerging in different geographical regions of the world. Until proven otherwise, their emergence is likely due to the founder effect. Let’s say a virus with D614G emerges during replication in a person’s respiratory tract. If viruses with that change infect the next person, and the next, and so on, then the D614G change will predominate. The change is simply a single nucleotide polymorphism of little consequence. It is the noise produced by error-prone RNA synthesis by the virus. Viruses with D614S are simply virus isolates. They are not strains of SARS-CoV-2.

Because of the founder effect, showing that a particular mutation increases viral transmission in humans is very difficult. Many such claims have been made for other viruses in the past, but none have been proven. One that comes to mind is a single amino acid that emerged in the Ebolavirus glycoprotein early in the 2015 West Africa outbreak and was subsequently found in all isolates. No proof emerged that it was not simply a founder effect.

I would also caution that making claims that SARS-CoV-2 is becoming more transmissible ignores the fact that the virus is already exceedingly transmissible among humans. For an amino acid change such as D614S to be positively selected, as opposed to being maintained as a consequence of the founder effect, requires selective pressure. For such an already highly transmissible virus, the nature of such selection pressure is difficult to discern.

Comments on this entry are closed.

  • Michael Novakhov 11 May 2020, 3:11 pm

    Dear Vincent, a question for you:
    Coronavirus D614G subtype Founder Effect – is it an indication that Sars-Cov-2 came from Germany, and not from China?
    M.N.

  • Valerie 11 May 2020, 10:27 pm

    When is Covid19-19 be over?

  • Turhan 13 May 2020, 12:26 pm

    “Because of the founder effect, showing that a particular mutation increases viral transmission in humans is very difficult.”
    Can someone explain this statement?

  • David Cotton 14 May 2020, 2:38 am

    So far we have only identified one strain of sars cov 2.

    We haven’t had time to do sufficient studies on the genomic variants to sufficiently determine if they differ in any fundamental biological property, yet.

    So we don’t know if there is more than one strain or not.

    There are preprints that claim some isolates do indeed have different properties and would therefore could be different strains, if confirmed via the scientific review process.

    So technically you’re correct. We’ll only get the actual answer in the future.

  • ethel deitz 14 May 2020, 6:57 am

    appreciate your knowledge but your accusatory tone and lack of citation makes you less credible in my opinion.

  • Tony 21 May 2020, 2:49 pm

    In virus taxonomy, which of the two, strain or isolate, is in the category of “individuum”?

  • Chris Zilch 24 May 2020, 7:53 am

    Dear Vincent, fully agree with your view on the “strain”-definition. However, all evidence so far points towards a possible functional role of the non-synonymous D614G mutation within spike. I have been following it since its first appearance mid – end January starting in Wuhan – Shanghai – Germany – rest of Europe – ww.
    At first it was just one of many “random mutations” within the CoV-2 sequence, but it slowly became the dominant variant in many parts of the world – even in phylogenetically unrelated viral clades (check NextStrain.org for A23403G in almost 69% of all isolates around the world). This observation cannot be explained by a “founder effect”, especially since there is growing evidence for a possible function within spike.
    Three possibilities have been suggested so far: 1) loss of an immunogenic epitope, 2) advantageous change in the glycosylation pattern, 3) gain of proteolytic cleavage site (neutrophil serine protease elastase), which would provide CoV-2 with a selection advantage in addition to the existing Furin-cleavage-site at S1/S2 border.
    My suspicion is, which is of course purely speculative, that CoV-2 variant D614G utilises Elastase for spike processing following neutrophil infiltration that express proteins at a very high levels to flight off infections. The more abundant host proteases (applies for Plasmin and Elastase apart from Furin, TMPRSS2, Cathepsin L und Trypsin) the more likely it is that spike is processed as a prerequisite of the virus to expand its tropism. Clearly this needs to be confirmed using viral replication assays, but there is already some indicative literature from CoV-1 research.
    You mention that a positive selection requires some selective pressure. Not always: The predominance of D614G may just be a result of its faster transmission kinetics due to accelerated viral replication resulting in higher viral loads and contagiousness of its infected host. The last word has not been spoken in this matter.

  • James Gallagher 26 May 2020, 5:50 am

    Claims of non-existence are generally harder to evidence than existence. I can’t see any evidence presented here for the non-existence of distinct strains.

  • Adam Brufsky 1 June 2020, 12:05 pm

    It is ok to be wrong. We won’t hold it against you. It’s the way of science, after all.

    https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25902

    https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25980

    https://www.medrxiv.org/content/10.1101/2020.04.14.20060160v2

    Cheers, and I hope you and your family are safe and well.

  • Robert Goldman 4 June 2020, 6:35 pm

    A change in genotype may cause a change in its phenotype. Or it may not.

    There are already thousands of different SARS-CoV-2 genotypes profiled in the GISAID database. How would we know for sure if one (or more) is expressing a distinctly different phenotype or not? By doing studies to compare the phenotypic expressions of different genotypes.

    If studies show different genotypes have distinct phenotypic expressions – then we prove the existence of different strains.

    If studies show that ALL genotypes have the SAME phenotypic expression – then we prove that “there is only one strain of SARS-CoV-2”.

    If there are no studies to prove either, then the correct statement is:

    “We don’t know whether there are different strains or not. There could be. Or they may all be the same.”

    I find your assertion that “There is one, and only one strain of SARS-CoV-2” to be maliciously misleading. They have to prove their case. But you don’t have to? Your word is truth without having to show evidence? What kind of scientist are you?