EXPERT REACTION: Does Adelaide have a "super-strain" of COVID-19?

What exactly are “strains” and what difference do they make to the virus?

Strains are variants of a virus that differ genetically from other 'strains'. They may also differ in  behaviour, and if they differ enough then the virologists studying them might give them a new strain name. So the new strain can be found by sequence differences or by behaving differently (and then subsequently being found to have sequence differences). It's the working virologist who decides - the number of differences in their genome varies greatly - no rules except the greater the number the more likely they are to behave differently

What makes something a '”new strain” versus the small differences found in genomic testing? 

There are no rules for most viruses - it's 'in the eye of the beholder'.  

SA health authorities claim they are fighting a particularly virulent strain of the virus with a shorter-than-usual incubation period and fewer symptoms. Is there evidence to support this claim and have such 'super-strains' been detected elsewhere in the world? 

The virologists in SA are the people who would know if the differences they see are useful to record by giving the new strain a new name. Usually increased 'virulence' means that the virus is more damaging, but could be used for shorter incubation period and fewer symptoms. 

We know that all RNA viruses mutate to some degree but we need more data before we say this is a new strain, which is more virulent. Mostly like this is the same strain (D614G) circulating in Europe and other countries. Rapid increase in cases is likely due to exposure of too many people in a very short period of time, as we’ve seen during the Melbourne outbreak. We learnt some good lessons from the Melbourne outbreaks so hopefully we will be able to control the South Australian outbreak with a rapid response.

Coronaviruses can mutate, but are much more stable than influenza. There has not been any genetic data published to show mutations in SA at this stage. If the outbreak originated from a returned traveller in hotel quarantine, it is likely from the UK or Europe, and may be the M439K variant which is circulating in Europe. It has been reported this strain may be more infectious.

The observation of a very short incubation period was also seen at the Crossroads Hotel outbreak in Sydney, and there was no unusual mutant in that case. A short incubation may arise simply from a high exposure dose (it’s called dose-response relationship). There may have been a superspreading event with high viral shedding and resulted in high dose exposure. This could also result in a short incubation period. My guess is, the SA cases with short incubation periods have been exposed to high doses of the virus.

At this stage, based on global phylogeography, there is no evidence of a vaccine escape mutant. Most vaccines target the immunogenic spike protein, and so far there has not been evidence of changes to the spike protein that would stop an immune response to that protein. The D614G strain became the dominant global strain many months ago, and involves a switch in one amino acid in the spike protein. It may be more easily transmitted but is not more severe, and vaccines will still work against it.

In terms of asymptomatic cases being highly infectious, that is not surprising. Numerous studies show that the viral load in people with and without symptoms is equally high. Even in people who have symptoms, viral load is highest in the 2 days before symptoms start. The problem is, there has been a reluctance to accept asymptomatic transmission, starting with WHO denying it a few months ago, and many guidelines still stubbornly focused on symptomatic testing only. It’s time to accept that asymptomatic transmission is significant, and if we don’t adapt our testing and control mechanisms to address this, we will fall behind in disease control.  So, all close contacts should be tested, regardless of symptoms. I read a report that people without symptoms were being discouraged from testing initially. There is a huge body of evidence showing substantial asymptomatic transmission of SARS CoV 2. That has nothing to do with mutations - it is a diabolical feature of this virus that we need to accept and deal with.

It is unclear what the South Australian Chief Health Officer is referring to with a new strain in the current outbreak. There is no genomic data for the scientific community to verify such a claim, where a new strain has a specific definition. Moreover, the circulating UK strains aren't different from what is circulating in other areas, suggesting it is unlikely there is a 'UK super strain'. Of course a novel strain might have arisen very recently so we await the evidence.

The new 'strain' is also described as being much more infectious than before but we know the natural course of SARS-COV-2 infection is 1-14 days post-exposure, so this is not any faster than what has previously been observed. It is far more likely this is super spreader event for which we have seen previously. 

The actions taken by the SA government in acting quickly to implement a 6-day lockdown to stop the spread is consistent with an elimination strategy. However the stated strategy in SA is suppression and so these actions are inconsistent with that approach. Other states also have a suppression strategy but have implement control strategies that are more consistent with elimination.

What exactly are “strains”?

"Experts in the area prefer the term 'variants' - each is a virus from a different person, or group of people (forming a 'lineage' when their sequences are compared to other members of the same virus), which have undergone a small amount of discriminable genetic change during their infectious travels."

What makes something a '”new strain” versus the small differences found in genomic testing?

"Strains usually differ by a larger number of protein-affecting genetic mutations."

SA health authorities claim they are fighting a particularly virulent strain of the virus with a shorter-than-usual incubation period and fewer symptoms. Is there evidence to support this claim and have such 'super-strains' been detected elsewhere in the world?

"The authorities seem to be describing an incubation period of 24 hours. That would be short. It may be that it has been difficult to accurately identify when one person was infected by another in a large family setting with many shared surfaces and airspaces providing lots of opportunities for transmission. A superspreading event may also have occurred, with varying incubation periods among the infected, making the determination of the occurrence of infection harder to interpret. We are still early in this cluster and need to gather more evidence. In the meantime, we need to be careful not to be overly speculative."

What do we know about the current strain in the Adelaide COVID-19 cluster?

"Not enough info to draw any firm conclusions yet."

What do we know about COVID strains circulating across the world, including the D614G strain?

"For now, SARS-CoV-2 and its variants can still be considered as a single 'virus'. It's like all of the world's human genetic diversity still sitting under the umbrella of one species. As far as we know, all SARS-CoV-2 variants react to antibodies raised against any of them and their sequences don't dramatically change the proteins they encode. Most of what we read about in terms of 'new strains' is mostly about small genetic and sometimes amino acid (affecting the protein) changes, the impact of which is either unknown or not obvious. In the case of D614G, this change allows the virus to spread a little more effectively according to lab work and the observation that it has been so globally successful. But as SARS-CoV-2 virus spreads in different areas and onward among people, it continues to evolve and so vigilance remains essential. Beyond simply cataloguing their occurrence, it's also really important that we continue to examine the impact of amino acid changes among SARS-CoV-2 variants, through study in the lab."

Strain vs Isolate is best covered here:
https://www.virology.ws/2020/05/07/there-is-one-and-only-one-strain-of-sars-cov-2/
 
SARS-CoV-2 is estimated to mutate at a relatively low rate of 0.80- 2.38 x 10-3 nucleotide substitutions per site per year, and this leads to a collection of viral isolates that may be slightly different. Changes in the spike glycoprotein are the ones of most concern, as they indicate the virus may be entering cells more efficiently or escaping/ becoming more resistant to an antibody response.
 
D614G is hypothesised to have become more fit and able to enter cells more efficiently. Currently this version represents more than 80 percent of infections worldwide.
 
An additional change was seen in the isolate primarily expanding in Victoria in the second wave. This was S477N in addition to D614G. The present hypothesis for S477N is that it binds the ACE2 receptor with greater affinity. This needs confirmation and neither D614G and S477N have been studied in depth in their ability to evade the immune response. That is to say, we do not know if these changes will impact vaccine development. At the moment, S477n + D614G are estimated to be around 5 percent of infections globally and the dominant Oceanic variant.
 
My colleagues and I are not aware of the Adelaide virus sequence. It would be good to know and to let others know if it is beyond what was observed in Victoria (or globally for that matter) and if there is evidence from other places in the world that this virus does represent an increased risk.