How Covid-19 is changing the flu

12th October 2020

Humanity hasn’t always lived with the flu. Could this era of social distancing hasten its demise?

It was the first time the Sapanawa tribe had ever made contact.

The meeting occurred in the remote Serra do Divisor National Park – a vast area of the Amazon basin in the far west of Brazil. From the sky, it looks like a uniform stretch of unbroken forest; concealed beneath are waterfalls, rivers, dormant volcanos and human villages. This is a place where giant armadillos, tapirs and jaguars roam the landscape, and uncontacted peoples live largely as they have done for some 32,000 years.

But for one isolated tribe, everything changed in 2014. Several members of the Sapanawa strayed out of their time warp after fleeing violent attacks from logging gangs across the border in Peru. They raided the village of another remote tribe, who had settled down and made contact with modern civilisation decades ago. Afterwards, they spent three weeks in the company of FUNAI, a government body that protects indigenous people from the outside world.

Indigenous Amazonians are anomalies in almost every way – they speak ancient, little-known languages, some of which lack words for numbers and even colours. Their societies are often egalitarian. And they are also among the only communities on Earth not to suffer from the diseases which plague the rest of humanity. Some uncontacted peoples – though not all – have never experienced the misery of having a cold or the flu, or other more life-threatening illnesses such as measles.

For the Sapanawa, this fragile disease-free state ended remarkably quickly after their first contact. Within days, many became gravely unwell; they had caught a respiratory infection, probably influenza. When tribes are first exposed to the flu, the fatality rate is usually extremely high. But on this occasion, there was a happy ending. The raiders received medical treatment and no one died, so after a brief period of quarantine, they returned home to their people. As far as anyone knows, this was the end of that flu epidemic.

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The presence of flu-free societies raises an important question: could the rest of the world ever be rid of this virus? As it happens, the world is making some tantalising first steps towards this goal.

Back in January 2020, at the end of the Australian summer, the country had 6,962 cases of the flu confirmed via a laboratory test. At this time, Covid-19 was still known only as “the novel coronavirus” and mostly confined to China. Ordinarily, you would have expected to see more and more cases of the flu as the days became shorter and winter descended.

Instead, something unexpected happened. By April there were just 229 cases of the flu – down from 18,705 at the same time the previous year. Covid-19 had already ripped across the world, collectively infecting more than a million people, including the British prime minister, and spreading to every continent except Antarctica. Lockdowns had been imposed, hand-washing had been popularised and mask-wearing had become commonplace – though the latter was still much more widely practiced in Asia than elsewhere.

By August, it was clear that Australia’s flu season had been the mildest on record. In all, there were fewer than a 10th of the infections seen in 2019 – and the vast majority of these occurred before the pandemic hit. This is all against a backdrop of more testing than had ever been conducted before.

The same pattern also occurred elsewhere. The co-head of South Africa’s National Institute of Communicable Diseases (NICD) recently told CBS News that the country “just didn't have a flu season this year”, while in New Zealand, doctors didn’t detect a single flu case during their annual screening drive, though last year 57% of the swabs they took were positive.

Many experts suspect that the trend is down to physical distancing and improvements to hygiene in the wake of the pandemic

Now winter is over in the Southern Hemisphere and beginning in the North. And though it’s still early in the season, already things look radically different to how they ordinarily would.

As of September, the World Health Organization (WHO) reported the missing flu cases were a global phenomenon, with significantly lower levels than would be expected, from tropical Africa to the Caribbean. For the week beginning 7 September, the flu tracker FluMart recorded just 12 lab-confirmed cases of the flu on the entire planet.

“What we’re seeing in Australia, New Zealand, South America, Hong Kong, are really, really attenuated seasons of not just the flu, but also respiratory syncytial virus (RSV),” says Sarah Cobey, an epidemiologist at the University of Chicago.

Of course, there are many possible reasons that cases might be down this year. People could be afraid to seek medical treatment, and in some places, there it’s possible that fewer tests were conducted as resources were diverted elsewhere. But many experts suspect that the trend is down to physical distancing and improvements to hygiene in the wake of the pandemic.

“We don't really understand it, but it may have to and may have to do with a little bit of changes in terms of how we interact with each other,” says Peter Palese, a microbiologist and expert in RNA viruses at Icahn School of Medicine at Mount Sinai, New York. “There is a possibility this might also continue in the future.”

This raises a number of questions. How is this new scarcity of flu affecting the virus? Is it even theoretically possible that it could permanently disappear? And have any other viruses been affected?

Humanity hasn’t always lived with the flu. It’s thought that we caught it from the first domesticated birds around 10,000 years ago, when people started to move away from hunter-gathering and switched to farming. For millennia, it was confined to the Old World, before eventually spreading to the Americas with the first European colonisers, who also brought with them a smorgasbord of additional diseases, including smallpox, measles, bubonic plague, malaria, leprosy, chickenpox, mumps, typhus, cholera, diphtheria and yellow fever.

None of these pathogens were permanently eliminated until 8 May 1980, when the World Health Assembly officially declared the world free of smallpox. The only other human pathogen that’s ever been pushed to extinction is Sars. The first effort relied on vaccination – and the second on contact-tracing. Unfortunately, neither approach is currently applicable to the flu.

Even if we could eliminate the virus entirely from the developed world, since we lack long-term immunity all it would take is a single case for it to come right back

“The big problem with influenza is that it changes,” says Palese. The virus is always evolving, so our immune systems are never able to recognise the virus for long after we’ve cleared an infection – and as everyone knows, this means we can be infected again and again; by one estimate, the flu affects up to 10% of the global population every year.

Which brings us to the bad news. On its own, social distancing is extremely unlikely to push the flu to extinction. “We have to really think here worldwide,” says Palese. “And even if all of the UK, the US and China wear masks, that doesn't mean that the rest of the world does it. And from what we have seen on television, not everyone in the US wears a mask.” Despite the low number of cases recorded this year, he explains that there will still be pockets of society where the virus is spreading as normal.

Even if we could eliminate the virus entirely from the developed world, since we lack long-term immunity all it would take is a single case for it to come right back. “Humans are distributed in such a way that flu viruses can do that – they just keep hopping around different populations without going extinct,” says Cobey.

However, this might not always be the case.

Because of the pace at which the flu evolves, current vaccines typically only protect people for around six months. To achieve these impressive feats of evasion, the virus relies mostly on “antigenic drift”, where a gradual build-up of mutations that affect the head of a viral particle – the part that’s usually recognised by the immune system – eventually change it enough so that it can no longer be identified as a threat.

This change typically occurs while it’s overwintering, so that it can hop back across to the opposite end of the globe once the season is over. (People who live near the equator are also infected at regular intervals, though these can occur year-round, rather than seasonally). At the moment, new vaccines must be developed every year, to match the viruses that are expected to circulate next; the composition of the Northern Hemisphere vaccine is decided in February, while the makeup of the Southern Hemisphere vaccine is chosen in September.

Enter the “universal flu vaccine” – a vaccine that you would only need once, and could protect you against all types of the flu, year after year. With such a tool, it would be possible to enact a mass vaccination programme and consign the flu to history. Right now, scientists across the globe are racing to achieve this goal – and after decades of research, we’re inching closer.

The challenge of a universal vaccine is to nudge the immune system in the right direction

Back in the 1980s, Palese and colleagues discovered that unlike the fickle “head” of the virus, the “stalk” is remarkably consistent – so antibodies that matched the stalk of one strain could also bind to – and therefore identify – others. The body can produce these antibodies naturally, but the head is larger and more striking, so the immune system tends to focus on identifying it and the stalk gets overlooked.

The challenge of a universal vaccine is to nudge the immune system in the right direction.

This is exactly what the not-so-catchily titled “H1ssF_3928” has been designed to do. In animal trials, the vaccine has already shown that it can provide immunity to H5N1 – also known as “bird flu” – though it was made from the stalk of H1N1, or swine flu. Now it’s in the first stage of human trials, in which people will be vaccinated and then monitored to see what kind of antibodies they produce. H1ssF_3928 is just one of many potential universal vaccines currently in development which, if they’re successful, could be rolled out worldwide.

But even here, there’s a catch.

The issue is that there isn’t just one flu virus – today the flu is a many-headed beast, with four main strains which circulate every year; two belong to the group influenza A, which is also found in other animals, while two belong to the group influenza B, which is only found in humans and seals. Occasionally, non-human flu A viruses will take the leap to infecting us, and cause a pandemic – such as the 1918 and 2009 strains, both of which may have come from pigs.

“A universal flu vaccine will only eradicate flu B, not flu A,” says Palese, who explains that even if you were to hunt down all of the flu A currently circulating in humans, new strains could still cross over from the reservoir in wild and domesticated animals. “So in terms of influenza A, we would have to constantly vaccinate the entire population, which is basically impossible. And if we don't do that, then animal strains, as I said, those in reindeer, those in chickens, those in pigs, those in horses, they can jump into humans.”

Palese gives the example of smallpox, which had the ideal features for elimination – the virus evolved slowly, and it had no animal hosts. Even with these advantages, it took nearly 200 years of vaccination to push it to extinction.

But though the flu is unlikely to disappear completely any time soon, the current pandemic might be affecting the virus in other ways. Here there are two possible scenarios – one of which is a lot more desirable than the other.

First up, the virus might be evolving more slowly than usual. This matters, because it means the strains we see next year wouldn’t be too dissimilar to the ones that circulated last year, and infections might be relatively mild. “I was talking about that with a colleague of mine recently,” says Cobey. “What's hard about influenza is that it's always evolving into something new that we've never ever seen before. And so it's actually very hard to say, ‘if things were a little bit different, it would evolve like this’, because it's kind of so unpredictable to begin with. But this could be really good – it’s exciting,” says Cobey.

“It's really simple,” says Palese. “If there’s less virus around, fewer mutations happen.” He explains that if you have 10,000 infected people, statistically speaking you would expect 10 mutations to emerge. So if you had just a thousand, you would expect a 10th of that number.

Theoretically, anything that affects the amount of virus circulating should affect its evolution – even the flu vaccines that are currently available. “If Bill Gates [the billionaire philanthropist and co-founder of Microsoft, who has helped to fund the eradication of polio] would pay for it, and then 95% of people would agree to have it, then I think that kind of immune protection would then result in a different Darwinian selection,” he says. “But on the other hand, only around 5% of the world population gets vaccinated,” says Palese.

If there’s less virus around, fewer mutations happen – Peter Palese

However, there is another possibility.

In reality, we don’t know for sure if social distancing has led to fewer flu infections worldwide – or just the number recorded. If it hasn’t, the rate of its evolution might be largely unchanged. This would mean that next year – when social distancing may have been largely abandoned – parts of the world that currently have fewer flu cases could be hit hard.

“If there's no transmission of other respiratory pathogens, that means people are not getting immunity to them,” says Cobey. “One thing I really am worried about is what will happen to these other pathogens once there’s a [Covid-19] vaccine.”

Cobey suggests that, instead of focusing our efforts entirely on developing a vaccine, it would be helpful to take the opportunity to invest in the types of prevention and treatment that can also work against other respiratory pathogens, such as improvements in hygiene and access to ventilators. “So that maybe when we have that vaccine, we don't have to go back to exactly how things were before,” she says.

Palese, on the other hand, is keen to stress the importance of getting vaccinated against the flu. “Even if it is not completely protective, it is certainly resulting in a more mellow disease – and it’s a very safe vaccine,” he says.

Crucially, scientists don’t yet know what happens when people are infected with Covid-19 and the flu at the same time. “We really don't know. I am very worried that it might increase the severity of the disease," says Palese.

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