Professor Sharon Peacock is acutely aware that in her line of work there is “a fine balance between calling it right and unduly panicking people”. She is the executive director and chairwoman of the Covid-19 Genomics UK (COG-UK) consortium, which means she is on the frontline of looking at new variants of coronavirus and discussing what the appropriate response to them is. It also means that she goes to a lot of long, politically-charged meetings — where her colleagues do not always agree.
“We had a meeting about the Indian variant that overran by at least an hour because there was so much debate as to whether we would escalate the seriousness of the threat posed by the variant or not,” says Dr Christina Atchison, who leads Public Health England’s rapid investigation unit. “The majority of us felt we should err on the side of caution but there was a lot of discussion. I’d have been inclined to wait two to three weeks before easing lockdown on May 17 until we knew more — it takes two to three weeks to grow the virus in a lab to understand it — but I appreciate there are political and economic considerations.”
There was always going to be a degree of uncertainty when dealing with a new virus but the timing of the Indian variant’s emergence (now called Delta) has been particularly painful as businesses are only beginning to bounce back and people’s hopes are pinned on the easing of restrictions on June 21. As a variant from Nepal is detected in Europe, Sir John Bell, a leading member of the Oxford/AstraZeneca vaccine team has warned that the country cannot “scamper down a rabbit hole” with every new variant. He says that Covid is probably here forever and the Government should focus on managing hospitalisations, serious disease and deaths rather than cases. Professor Peacock says: “You feel a level of concern [with new variants] but we have years of this to come. I am glad I don’t have to make the political decisions.”
At the moment, the uncertainty comes from us still working out how new variants of Covid react to vaccines. Early studies are promising but Professor Peacock, Dr Atchison and their colleagues are working as quickly as they can to find out as much as they can.
“Mutations are to be expected — viruses always do evolve in order to survive,” says Dr Atchison. “But Covid is so new and we don’t know how it reacts to vaccines.”
A mutation is a genetic alteration in the protein that makes up a disease. Each time the virus replicates in someone’s throat it has the opportunity to mutate and there are around two new mutations of coronavirus a month, but it is the position of the mutation, not its frequency, which matters. “You only need one mutation in the right place on the virus to make a difference,” says Professor Peacock.
She set up COG-UK when the pandemic began amid opposition from those who said that coronavirus does not mutate as fast as HIV or flu so there was no need to have a special body to sequence its genomes. But Professor Peacock didn’t want to risk it and wait until the worst case scenario happened, only to find that we were not prepared. “It wasn’t difficult to realise that the virus was going to mutate and this was something we should think about for the future,” she says. “Pathogens evolve, it is survival of the fittest to help them survive.”
When she saw in the news that there were a large number of coronavirus cases in India back in early March, she says her “ears pricked up”. What she and her colleagues needed to work out was whether the virus was spreading because of the way that people were behaving or because of a particularly transmissible new strain. There are actually three related variants in the UK associated with India but they realised within a couple of days that just one of them needed to be watched closely.
“What we want to see is that we can track a case and link it to other cases in what we call a cluster,” says Dr Atchison. “If we are able to do that it provides reassurance that the events are in that group. What we don’t want is too much of a delay between getting a positive test and knowing it is linked to a cluster because then it may have been transmitted already.” Dr Meaghan Kall, lead epidemiologist in PHE’s COVID-19 Epidemiology Cell, monitoring the number of cases and deaths and, more recently, COVID-19 variants. A typical day is a 12-hour shift starting at 8am. “We do a huddle to task work to scientists for the day, prioritising urgent tasks - which feels like most of our work at the moment. I check and sign off outputs like slides and datasets which get sent to local teams and JBC, DHSC, SPI-M and SAGE. For variants, on a daily basis we take genomic sequencing results and enhance them with demographic and clinical data to be able to describe the populations affected and examine outcomes like increased transmissibility and severity.”
Scientists at PHE are working 75-hour weeks and Professor Peacock says she is grateful to the academics who have put their PhDs on hold to commit to sequencing, and to their families for putting up with their long hours. Last Christmas they were all in the lab.
Dr Atchison says with a laugh that she was “hoping for a quieter summer ... but then something puts a spanner in the works”. Her “bread and butter” used to be TB, measles in school and scabies and flu in care homes, but for the foreseeable future it will be Covid. They agree that it is something we have to learn to live with. “We have to get into a beat of looking at it, understanding the impact and learning to live with it,” says Professor Peacock.
The concern is that other countries without such advanced laboratories may not be able to find out so much about their variants until it is too late. “I worry a lot about variants from areas where there is insufficient sequencing capability, meaning we may not know about the variants until they come over here,” says Professor Peacock. “Until all countries get a grip on this it is unlikely we will see the end of this,” says Dr Atchison. “Shutting borders to everyone all the time is not sustainable. While Covid is rampant in other parts of the world we will see things like the Indian and Kent variants happening.”
The UK is leading the world on genomic sequencing of Covid — by December last year, the UK was responsible for half of all the world’s genome sequencing of coronavirus. The samples came from hospitals and the community and they try to work with offices too but get more pushback (it is not obligatory to give them). In 2013, it would take 18 months and half a million pounds to sequence one genome. Now it takes a few days and costs £20 because they have expanded the scale at which they work and the tech has improved. There are 400 people in the COG-UK consortium and they run 15 sequencing labs in academic institutions across the country.
“It is a revolution. We are sequencing on a scale we have never done before,” says Professor Peacock. Jenny Harries, head of the UK Health Security Agency, has said this is an opportunity for science. “Never before have politicians been so keen to throw money at us,” says Dr Atchison. “I can see how this is an opportunity to make a really strong case and build a public health system.” Many of the top scientists are women, which Peacock says is “tremendous” and getting younger people interested in careers in science.
The programme that is used now was set up when the Kent variant broke out, back then “it was a scramble to get new information”, says Dr Kall, “but we learn more with each new variant”. After Kent, Dr Atchison was given the green light to enlarge her team from two people to eight. Professor Peacock was also allowed to increase the capacity of tests, It was harder to work out where that variant had come from than the India variant, says Dr Atchison, who at one point “wondered if everyone in Kent had been to an illegal rave”. It turned out the virus mutated in one patient.
The scientists are aware that naming variants after areas can lead to prejudice and so it is good news that the variants will now be referred to with Greek alphabet letters. “We don’t call Covid the China virus,” says Dr Atchison. “Apart from the pain of having to learn a new naming system, I think this is a positive development,” says Dr Kall. “It’s crucial that the public are able to easily name and identify variants and even experts can struggle with the complicated alphanumeric names. I’m going to have to work on my Greek though!”
What is the best way of reducing mutations? “Controlling disease,” says Professor Peacock. Ventilation makes a big difference. Dr Atchison looked into a block of flats in east London where the Brazilian variant spread through the airflow system and the same happened in a quarantine hotel in New Zealand.
Thankfully there are no new variants of concern at the moment. There is a Californian one that has been on the list for a long time but it hasn’t been reported of a particular concern and there was one from Nigeria which was found in Antigua but it hasn’t been seen since. The next step is to work out how to de-escalate. “How do we take things off the list and give local teams a bit of a break?” asks Dr Atchison. “The problem is when there is so much uncertainty. The winter will be interesting. I am hoping it will be like flu — it will be there but you only clamp down if it is in a vulnerable setting like a care home and the political and scientific hysteria will decrease. And then we can all have a bit of a break.