By Michael O’Farrell
Investigations Editor
ACCELERATING Covid-19 mutations may be on the way to making the virus immune to treatments and vaccinations, a leading member of NPHET has warned.
‘While they may not be resistant at this point in time I think the concern is that they may be on the way to being resistant,’ Dr Cillian De Gascun told the Irish Mail on Sunday. He warned that the virus has mutated faster and in more diverse ways than expected.
‘They have far more mutations than we would expect at this point in time,’ he said.
‘We don’t yet know why these variants have acquired more mutations – and more significant mutations certainly in the spike protein in the last number of months.
‘From a virology perspective and an academic perspective – and in the context of the pandemic – it’s important to try and figure out where they came from.’
Dr De Gascun said the reasons for the speed of new mutations remain unknown though it could be thanks to the virus seizing an opportunity to mutate in an immunocompromised patient.
‘There’s been speculation that this may have happened in the context of a persistent infection, perhaps in an individual who’s immunocompromised so therefore the virus had plenty of opportunity to replicate in the setting of a sub-optimal immune response,’ he said.
‘Another possible explanation – because we would have seen this in the Danish mink – is that those viruses may have spent some time in an animal host and may have been exposed to a different evolutionary pressure.
MUTATIONS UNCHECKED. Despite unprecedented scientific endeavour and collaboration, humanity remains blind to many of the Coronavirus mutations occurring globally. That’s because many countries – particularly those in Africa and south America – are not carrying out any monitoring for new strains. of the killer disease at all. The UsA – despite its wealth and scientific prowess – also remains a troubling blindspot with 26 million Covid-19 cases and no robust system to track or identify Mutations . In all of Africa, where more than 3.5 million Covid infections have been reported, just 5,000 samples have been genome sequenced in only 24 of the 47 countries in the region . That means that like the UsA, half of African countries are blindspots from which a variant’ of concern could already be circulating unknown. Added to this lack of monitoring, the recent surge in infections has significantly increased the opportunity the virus has to mutate.
‘There’s no evidence of a link between the variant and an animal host but we don’t yet know why these variants have acquired more mutations – and more significant mutations certainly in the spike protein in the last number of months.’
Dr De Gascun, the head of the National Virus Reference Laboratory, also confirmed that health authorities here are treating two recent travellers from Brazil as possible carriers of the main Brazilian variant of concern.
Known as P1 the variant was first found in travellers arriving into Tokyo from Brazil three weeks ago.It has since been traced to the city of Manaus in Brazil’s Amazonas state amid concerns that it may have the ability to reinfect those who have already recovered from Covid.
The two possible Irish cases were among the more than 2,000 travellers who have arrived here from Brazil since Christmas week.
Of these just 604 have come forward for testing, from which 52 tested positive.
All positives were then sent to the National Virus Reference Laboratory for RNA sequencing to check if they carried the same mutations as any of the main variant’s of concern that have been linked to the UK, South Africa and Brazil.
As a first step the Laboratory runs a test to see if one key mutation common to all three variant’s of concern – known as 501Y – is present .
If the 501Y mutation is detected a full RNA sequence is then run to check which variant’ is present .
But for technical reasons the Laboratory was unable to run a full sequence for the two travellers from Brazil to confirm which variant was present .
‘For those two we weren’t able to generate a sequence,’ Dr De Gascun told the MoS.
‘They had a travel history. They had the 501Y but the viral load was too low to actually generate a sequence,’ he said.
‘From a public health perspective they’ve been managed as possible cases – but we certainly haven’t confirmed them as being the new lineage.’
Ireland has, though, confirmed four cases of a second less-potent Brazilian variant of concern. known as P2 – one in Mullingar in Co. Westmeath and three in Dublin.
This variant’ does not contain the dreaded 501Y mutation and is therefore considered less potent though it does share another mutation – known as 484K – with the main Brazilian variant .
The National Virus Reference Laboratory (NVRL) shared the details of these cases with the international scientific community via the GISAID platform on January 17.
GISAID is an international scientific initiative through which global scientists rapidly share the RNA sequences of every influenza and CORONAVIRUS they find.
Traditionally, it is through this forum that the annual flu vaccines are derived, depending on the various new strains identified globally.
But now GISAID has also become the central clearing house in the battle to track the Covid virus as it evolves and mutates. And the sequencing of Covid RNA from positive cases is seen as the main weapon nations can deploy in this war.
Ireland, though, is not among the best-performing nations when it comes to sequencing. In this country there are two sequencing pipelines feeding into the GISAID system – the NVRL and the Irish Coronavirus Sequencing Consortium.
Funded by Science Foundation Ireland, the Irish Coronavirus Sequencing Consortium began sequencing coronavirus cases in August and has so far completed about 1,000 cases.
The NVRL is in UCD – which is also a member of the consortium – and has separately completed another 1,200 sequences.
In all, Ireland has sequenced just 2,271 of its 194,000 Covid cases – about 1.1%.
In contrast, Australia, the world leader, has managed to sequence 58% of its Covid cases.
New Zealand, Taiwan, Denmark and Iceland are also at the top of the list having also ploughed significant resources into tracking mutations .
The UK has invested £20m into its Sequencing Consortium. and has so far tracked more than 146,000 cases – amounting to a little over 7% of all Covid cases there.
Ireland, meanwhile, has put just €378,716 towards sequencing by way of a Science Foundation Ireland grant.
With such a paucity of funding, the scientists involved – from universities and research institutions across the country – are actually working for free with the grant being used for consumables that are required for the sequencing procedure.
Private sector firms – such as Genomics Medicine Ireland – are also providing free sequencing to the consortium on their equipment.
Speaking to the MoS, consortium leader Dr Paul Cotter confirmed scientists were working for free.
‘Yes. The funding we received from SFI was used exclusively for consumables,’ he said.
‘We’ve been able to make this go a long way thanks to reduced-cost consumables provided by some of the suppliers.’
Now though it’s hoped Ireland will expand sequencing efforts – something Dr De Gascun said has been approved by the HSE.
‘The general guidance from ECDC [European Centre for Disease Control] and from WHO is that ideally you’d like to be in theregion of between 5-10%,’ he said.
‘That’s really been part of our plan over the last number of months. – 1% is decent but there is broad agreement that we want to increase that capacity.’
Dr De Gascun said it was vital to ‘figure out why and in what settings’ new variant’s are emerging and why some of the same mutations were occurring independently in different parts of the world.
‘It’s obviously identified this amino acid change at position 501Y and it likes it,’ he said.
‘We’re still a new host for this virus. It’s obviously been a long year for us and we’ve found it very difficult but from a virus perspective it’s still adapting to us as a new host and it looks like it might be approaching something that might be its optimal configuration.’
Now, the other key challenge for scientists is to monitor how the virus reacts to vaccines.
‘The other concern is what’s going to happen as we roll out vaccines. That puts another pressure onto the virus,’ said Dr De Gascun.
‘We’re waiting to see what will happen when we introduce that factor and what will the virus do in that setting. That’s what we’ll be monitoring closely in the coming months and we’ll be looking at infections in people who have received the vaccine and that’s where the sequencing comes into play again.’
The Idiot’s Guide To Genome Sequencing
FOR something that’s caused such havoc around the world the coronavirus is a simple creation – something that allows it to be tracked relatively easily.
The human genome contains more than six billion letters of genetic code.
The coronavirus, however, has just 30,000.
On average up to two of these will mutate randomly each month – a far slower pace of mutation than the influenza or HIV viruses.
But since the coronavirus replicates itself millions of times inside each infected human there are untold opportunities for mutation to occur.
Already since the start of the pandemic tens of thousands of mutations – most of them inconsequential – have been spotted.
In fact, the virus has mutated so much that the original Wuhan strain has long ago been completely overtaken by new strains leapfrogging each other for survival.
To visualise how these mutations can be tracked via genetic sequencing an expert uses the analogy of a book with 30,000 words.
‘You could regard those RNA [ribonucleic acid] mutations as typos in various different sentences,’ explained Dr Paul Cotter, the head of the Irish Coronavirus Sequencing Consortium.
So a sentence therefore about a cat being in the room takes on a very different meaning if a single letter typo results in ‘cat’ reading ‘rat’. Imagine then that this typo gets repeatedly photocopied and widely distributed.
‘The fact that the sentence differs allows us to track the way the virus is moving around the world,’ Dr Cotter said.
Using a hand-held machine called a sequencer, hooked up to a laptop, scientists can take virus RNA left over from any Covid-19 test and easily read which letters have changed.
This can be done into the past – by reading test samples collected since the start of the pandemic – to trace back to how and where a strain first developed.
It can also be done on a live daily basis to monitor evolving mutations as they spread, Dr Cotter explained.
