It’s only midday, but virologist Lynne Whittaker has already been hard at work for five hours without a break, fully masked and gloved up while she runs tests in a laboratory that, for safety’s sake, is biosecure and firmly closed to visitors.
The reason for the caution is that she is analysing virus samples fresh off the plane from China. These are not, as you might expect, coronavirus samples, but nasal swabs from 15 people who’ve recently become ill with flu.
The tests that this senior research laboratory scientist is running will determine if this is a familiar virus or — more troubling — a new form that’s capable of causing a pandemic.
No visitor is allowed into the lab until the tests have been completed and the samples secured back into storage fridges, as these contain live viruses and could potentially cause infection.
We refer to ‘the flu’, but in fact there are three forms of the virus that infect humans — A, B and C, which are all different in structure. ‘The A viruses are the pandemic flu viruses — they, or parts of them, come from other species, such as birds or pigs,’ says virologist Dr John McCauley
This all sounds a bit alarming and even James Bond-esque: as I watch through glass windows, I feel as if I’m on the film set for a pandemic disaster movie. And all this for ordinary old flu.
Except that while to the scientists based here, at the Worldwide Influenza Centre at the Francis Crick Institute in London, it’s all in a day’s work, this is deadly serious stuff. These tests will help determine what goes into your flu jab.
As this winter’s vaccine rollout is set to be the biggest yet — with plans to vaccinate 35 million people compared to 19 million last year — this work is arguably more important than ever before.
As health secretary Sajid Javid recently warned, for the over-50s ‘getting your flu jab is going to be as important as having your Covid jab’. That’s because of fears we’re about to be hit by a high number of flu cases — Covid restrictions meant there were fewer flu infections than normal last winter, thus the population at large has ‘less immunity’.
In a typical year, around 10,000 in the UK die from flu, says Professor Andrew Easton, a virologist at the University of Warwick: ‘People who have flu are then susceptible to other infections — such as pneumonia — and the number of deaths can rise much higher.’
The strains derived from pigs
We refer to ‘the flu’, but in fact there are three forms of the virus that infect humans — A, B and C, which are all different in structure.
‘The A viruses are the pandemic flu viruses — they, or parts of them, come from other species, such as birds or pigs,’ says virologist Dr John McCauley.
‘These viruses from animals get into humans, adapt to humans, spread in humans, and then others from another species again might come in, and swap genes and often kick the previous flu A viruses out,’ he explains.
‘The B viruses are in no other animal species. They just evolve in humans.’
The A viruses account for about 75 per cent of infections. They are classed according to the subtypes of two proteins found on the surface of the virus: hemagglutinin (H) and neuraminidase (N): for instance, H1N1 (swine flu) and H5N1 (bird flu).
The main flu vaccine given each year contains protection against two A strains of the flu virus, and two B strains. A spokesperson for AstraZeneca told Good Health that including any more than four strains would lead to a less equal response, meaning the vaccine might protect against one type of flu better than the other.
Meanwhile, type C flu viruses are relatively rare and cause only a mild illness, so they are not taken into account when creating the vaccine.
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The surveillance centre at the Francis Crick Institute plays a key role in determining how effective the vaccine will be.
Established in the 1950s (in another London location), it’s one of seven around the world (the others are in Atlanta and Memphis in the U.S., Melbourne in Australia, Beijing in China, Tokyo in Japan and Siberia).
These surveillance centres are constantly analysing samples sent to them from around the world, to monitor the types of flu in circulation, how the common viruses are changing — and to keep their eyes open for the emergence of new, more troubling varieties such as the swine flu that appeared in 2009.
Each year the team at the Francis Crick Institute is sent 7,000 to 8,000 samples, collected using PCR tests conducted at some of the 150 associated national influenza centres dotted around the world.
‘Which country sends its samples where, is, to some degree, historical — we get samples from Europe, West and South Africa, central Asia and Hong Kong,’ says Dr John McCauley, a virologist and director of the Worldwide Influenza Centre in London.
He says there are millions of flu viruses in circulation each year, but as Lynne Whittaker explains: ‘If we see something new emerging from just one country, we don’t worry too much.
However, if you are spotting that a new mutation is all around the place, that’s when you worry.’
Based on their analysis, the centres must predict which strains of the flu virus may dominate in the months ahead.
Twice a year, 30 representatives from the seven global surveillance centres get together to share their information — and views — about which types of flu are most likely to pose a threat.
The meetings are held in February to decide what goes into the northern hemisphere jabs (administered from now) and in September to decide what goes into the southern hemisphere jabs (administered six months later).
It’s done this far in advance because it takes manufacturers up to six months to make the vaccine, says Dr McCauley.
These meetings aren’t a formality: the committee must agree on which flu viruses go into vaccines and there can be disagreement.
‘You have different views with regards to the recommendations,’ says Dr McCauley, choosing his words carefully. ‘But then if you don’t get a consensus we have a vote and the majority vote would then decide what’s done — you don’t always need it, but sometimes you do,’ he concedes.
In a typical year, around 10,000 in the UK die from flu, says Professor Andrew Easton, a virologist at the University of Warwick: ‘People who have flu are then susceptible to other infections — such as pneumonia — and the number of deaths can rise much higher
Between 2015 and 2020, the flu jab prevented 15 to 52 per cent of flu infections — some years it was less effective than others.
And with little flu in the community last year — there were no flu hospital admissions at all in some parts of the UK last winter — some have questioned how accurate the prediction will be this year.
If the scientists predict it right, it could save thousands of lives in the UK alone. If not, cases — and deaths — can rocket, as happened in the winter of 2014/15.
Earlier in that year, scientists from around the world had predicted that strains of flu that had been circulating in Texas and Massachusetts would be dominant. In fact, a Swiss strain became more dominant, and as a result, the vaccine was only 34 per cent effective in this country.
By January 2015, the viruses in the jab were so out-of-kilter with what was circulating that the effectiveness briefly dropped to 3 per cent, according to official data.
Almost 30,000 people in England and Wales alone died of flu and pneumonia in 2015, compared with 25,000 the year before.
In 2018, the vaccine was just 15 per cent effective — and this prompted a change in the make-up of UK vaccines, with the addition of an adjuvant, an ingredient that boosts the immune response, in the jab for the over-65s.
Is your bad cold really the flu?
These days, a nasty cough and flu-like symptoms seem to point to just one thing: Covid-19.
But the really bad cold and cough circulating at present is neither Covid — nor flu — but is caused by the respiratory syncytial virus (RSV), says Professor Ron Eccles, former director of the Common Cold Centre at Cardiff University.
‘I call it the ‘really stinking virus’ because the symptoms can be severe,’ he says.
This virus circulates every year, causing colds in most people but can cause serious chest infections, particularly in babies and the elderly.
‘Because we have had relatively few colds in transmission due to lockdown and social distancing measures for a year or so, our immunity to these viruses is not so widespread and we are all catching severe colds,’ says Professor Eccles.
‘RSV symptoms normally last for a week but the cough can persist for several weeks.’
He admits the symptoms are confusing because both colds and Covid are now circulating.
‘Most people who have been vaccinated are likely to have mild symptoms like a cold when they have Covid so it is not possible to separate Covid from colds just on symptoms,’ he says.
‘If you are staying home with a head cold for a few days until it clears then you probably do not need a Covid test, and only consider one if you start to develop severe symptoms such as difficulty in breathing.’RACHEL ELLIS
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Adding an adjuvant may cause more swelling at the vaccination site, as it creates a stronger response. However, suggestions that adjuvants such as aluminium salts may cause other health problems have been discredited.
Meanwhile, the main vaccine given to 18 to 65-year-olds was changed to protect against four types of flu, not three as before.
This seemed to pay off: the 2019/20 vaccines fared better, with as much as 64 per cent effectiveness for those aged 18 to 64, figures from Public Health England show.But the problem remains that once that decision is made about what’s going into this year’s vaccines, it’s impossible to hit the brakes.
Cultivating the viruses needed for the vaccine and sourcing the components takes time, which means they can’t start again, even when the types not earmarked for the vaccine suddenly start to circulate more widely.
‘This came up in 2014 when some new viruses were identified probably at the end of March or beginning of April,’ says Dr McCauley. ‘But even then — a month after the northern hemisphere meeting had taken place — the process had gone too far to be able to stop.
‘The only alternative is that the Government could have produced a single element vaccine to prevent that new strain, but that didn’t happen,’ says Dr McCauley.
Making the prediction about which flu strain will dominate is, in many ways, an unenviable task.
As Professor Easton points out: ‘The difficulty is that the surveillance system is very elegant but trying to predict the strain that will cause problems in six months’ time is a very big ask.’
And predicting what lies ahead this year has been complicated by lockdown restrictions. During the last flu season (from October until April in this country) there was only one hospital admission for flu in Wales and Northern Ireland and one in Scotland; in England there were 131, compared to 1,691 the previous year.
Last month, Dr Beverly Taylor from Seqirus, a major manufacturer of the flu jab, said there was a ‘big reduction’ globally in labs supplying flu surveillance data and predicted ‘we could see a mismatch for at least one of the subtypes’ in the vaccine for this winter as a result.
But Dr McCauley prickles at the suggestion that the surveillance may be less complete than normal. ‘The amount of flu in circulation went down — but the amount of surveillance didn’t,’ he says.
Flu pandemics are not just a thing of the past
While the Spanish flu pandemic of 1918 was the most deadly, there have been other outbreaks of flu, as this timeline reveals.
1918: This form of H1N1 flu (known as Spanish flu, simply because this is where it was first identified) infected a third of the world’s population.
Around 50 million people died worldwide, and the 20 to 40 age group was especially badly hit because, it’s thought, they had not had prior exposure to similar strains of flu.
It killed 228,000 in this country — making it the first year deaths outnumbered births.
1957-8: Dubbed Asian flu, this H2N2 strain was first reported in Singapore in September 1957. Around 1.1 million died around the world, including 20,000 in the UK.
1968: Caused by H3N2, also known as Hong Kong flu, this was a form of avian flu that killed one million around the world and 30,000 in the UK. 2009: The H1N1 (swine flu) virus was first detected in Mexico and the U.S. It killed around half a million people worldwide, 80 per cent of them thought to be under 65, and killed 457 people in the UK. It’s now in common circulation and is regarded as a standard seasonal flu.
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‘Yes, OK, we are looking at a smaller pool [of flu virus] but you are still looking at the pool and asking if you can see anything new.
‘And yes we did, which is why the vaccine recommendation for the northern hemisphere included a new H3N2 [flu] virus.’
When a sample comes into the Francis Crick Institute, they first grow more of it — in small trays with a culture medium to encourage reproduction — so that there are plenty of samples to experiment with. On a scale of 1 to 4 (with 1 being low-risk infection such as E. coli and 4 being pathogens that can cause serious disease for which there is no treatment — and so must be worked on in a full biohazard suit), flu virus is a category 2, meaning the viruses must be worked on in a special biosafety cabinet.
The cabinet where Lynne Whittaker is working opens with a window that slides upwards.
She flicks a switch and there is a beeping sound — this means the protective air filter system is working. A wall of air then blows up and into a filter to try to stop stray virus blowing out into the room.
The morning Good Health visits, she’s working with red blood cells from ferrets that have been infected with known flu viruses and so contain antibodies — whether these antibodies lock on to the new virus or not will determine how much of a threat it might be.
Thankfully the newly shipped-in samples from China present no surprises — the antibodies in the ferret’s blood attach to them. Once they have the initial results, assessing if it’s a familiar subtype or not, the researchers conduct more in-depth tests looking at the genes of that virus to note any changes, for instance.
‘Influenza is mutating all the time,’ explains Lynne Whittaker, ‘and you have to keep on it because it can be fast moving.
‘When the flu season gets going in around December, right up until the vaccine meeting in February, we have to process as many viruses as we can — we may be analysing dozens of samples a day.’
New strains could pop up anywhere — although they tend to emerge in places with high populations such as Bangladesh, says Dr McCauley. If a new type of flu does turn up, the most important thing is to send samples of its genes to other surveillance centres so that they know what to watch for.
Some have questioned how open China was with sharing data about Covid-19, but Dr McCauley says he has no such concerns about flu.
‘I get sent Chinese flu numbers every week,’ he says. ‘We have just received viruses from them to look at — there’s no secrecy here.’
Dr McCauley is on the fence about how bad this year’s flu season will be, saying cases could rise due to low immunity. But ‘it’s also possible that as there has been little flu around last year we are starting from a low level so cases just won’t rise much’, he says.
He stresses, however, that even if a vaccine is moderately effective it can make a big difference.
‘If the vaccines are only 50 per cent efficient, that’s 50 per cent less flu in the community and so that is a considerable benefit for healthcare — even 30 per cent is good and 20 per cent isn’t to be sneezed at,’ says Dr McCauley.
‘You are trying to ensure the hospitals can still function — and vaccination is cheap. A vaccine costs £20 — the alternative of having people in intensive care is phenomenally expensive.’
Professor Easton believes it won’t be such a catastrophic year.
‘Historically, it takes about four years for the flu virus to mutate away the antibody protection offered by the infection or the vaccine,’ he says.
‘So while you should get a new vaccine every year, the historical immunity [from previous years] you have will provide some degree of protection,’ he says.
But we should not lose sight of the threat that flu poses.
‘Flu is a dangerous virus — and I think we have become a bit relaxed about it,’ adds Professor Easton. ‘There is every chance that a flu pandemic will come along that will be as devastating as the one that hit in 1918.’ (see box above)
Dr McCauley adds: ‘The big concern is what happens when such a strain does spread — with a death rate that will make Covid look trivial.’
Is he worried about being able to protect us? ‘We don’t very often get this stuff wrong,’ he says, reassuringly. Let’s hope for all our sakes that he is right.
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