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

96 Comments / By Vincent Racaniello / 7 May 2020

The 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.