With some recent tightening of restrictions caused by cases of the highly infectious UK variant, how do we know what strains of COVID-19 are out there and how can we be sure testing is effectively picking up new strains? The answer is genome sequencing.
What is genome sequencing?
Every living thing is made up of genetic material, DNA or RNA, which contains the code for how that thing is made and functions. The genome is the entirety of this code, which is unique to each individual and expressed in the letters CGAT.
If we think of this code like a large book filled with letters; sequencing the genome is decoding the entire book, compared to other types of genetic testing which might examine just a few specific pages or chapters.
The process to sequence a genome is similar whether it is for a human, a plant or a virus. The major difference is that the human genome is much, much bigger and more complex than the genome of a virus, which is why it takes a lot longer to sequence the human genome and analyse the data.
Why do we need genome sequencing for COVID-19?
The virus needs to be sequenced so that a diagnostic test can be made for it, and to track how it is changing over time.
SARS-CoV-2, the virus that causes COVID-19, first appeared in China. When existing pathology tests ruled out known pathogens, such as influenza, scientists needed to sequence the viral genome so they could determine that it was a new type of coronavirus, and then develop tests to detect it in humans.
The gold standard test used in Australian pathology laboratories for COVID-19 diagnosis is a polymerase chain reaction (PCR) test. The test takes a sample from the nose and throat of the patient which will contain the virus (if it is present), and applies a technique that will cause viral RNA in the sample to be amplified (copied many times). This can then be detected by the PCR instrument.
The PCR test looks for specific targets in the genetic code of the virus and these targets can only be identified, and this specific test created, once the viral genome is known.
I tested positive for COVID-19. How do I know which variant I have?
For most patients who test positive – you won’t know what specific variant of COVID-19 you have. This is because, so far, little clinical difference has been reported between variants. That means that what you should do as a patient to look after yourself and others, and how doctors treat you, won’t change depending on which variant you have.
Although a PCR test can spot certain anomalies in a sample that would indicate the likelihood of a specific strain, the only way to accurately determine which variant the patient is infected with is genome sequencing.
For example, the UK variant known as B.1.1.7 has a particular genetic change identified as H69/V70 deletion. This shows up on the PCR test commonly being used in the UK because it affects a particular part of the spike protein’s genetic code that the PCR test is looking at.1
When pathologists and medical scientists analyse the test result; they can still detect the presence of SARS-CoV-2 because the test is looking at more than one section of code. Upon seeing the deletion, they might also refer those samples for genome sequencing.
What strains of COVID-19 are circulating in Australia?
The World Health Organisation (WHO) reports that a new variant of SARS-CoV-2 emerged in late January or early February 2020, the D614G strain.
In the following months, this replaced the initial SARS-CoV-2 strain identified in China, and by June 2020 it was the dominant form of the virus circulating globally2. The first COVID-19 cases in Australia began appearing in late January 20203 and by May 2020 around half of the virus samples sequenced in Australia carried the D614G mutation.4
Because mutations in the virus are so common and usually do not impact public health advice, the WHO collects and disseminates information on any variants that are reported to have a bearing on how the virus spreads, or clinical implications such as the severity of symptoms, mortality rate and response to treatments and vaccines.
WHO has published information on two ‘variants of concern’ the B.1.1.7 variant which is now widespread in the UK, as well as a variant identified in South Africa known as 501Y.V2. This is similar to the UK variant, but genome sequencing has shown it is distinct from that strain.2
So far, cases of the B.1.1.7 variant first identified in South East England have been reported in Australia and are all linked to hotel quarantine. The South African variant has also spread to other countries, and a small number of cases within the same family unit have been identified in hotel quarantine in New South Wales.
Pathology teams are committed to tracking the virus and suitable samples taken from people coming from overseas are used for genome sequencing. So far, about 8,000 viral genomic sequences have been performed in Australia since the beginning of the pandemic.
The sequences are uploaded to a database known as AUSTRAKKA. These data are used to track outbreaks as well as identify what variants travellers may be bringing into the country.
How do we know that pathology tests can find all the different COVID-19 strains that are circulating?
The pieces of genetic information that the diagnostic PCR tests look at have been carefully selected because they are fundamental parts of the virus and common across variants.
Although mutations occur all the time, these are most often minor changes that do not alter how the virus behaves or presents. The multigene PCR tests used in Australia can still detect the virus even with these mutations.
It would be almost impossible for a significant mutation to occur that affects all the parts of the genetic code targeted by the current PCR tests. To avoid being picked up by a 3 or 4 gene PCR test, those mutations would have to occur in all those targets that the PCR looks for, all at the same time. Such a mutation would be so significant it would likely be considered a new virus altogether.
The surveillance through genome sequencing picks up emerging changes in the viral genetic code, so mutations that affect test targets can be addressed accordingly.
IMAGE CREDIT: The Conversation