How to slip in two years

Why does the flu always strike when the 'R' is in the month?

It is an age-old riddle: Why does the flu always strike in winter? Because it's cold, of course. But the cold can't infect you, can it?

TEXT: FRANK BEIJEN – Quest

You wake up with a red-hot head. Has the heating been blaring all night? A second later, chills run down your body. And hey, it seems like you feel muscle pain in your arms. Uhmpf. You definitely have the flu. You quickly crawl back into bed and call your boss. 'You're already the fifth to call in sick today,' she says. 'I think it's prevalent.'

When a flu wave floods our country, it is always in the cold months. Usually, the number of flu cases starts to grow in October. The highest peak is often between December and February, and the flu only rages out around April. By that time, they will become ill in Australia and New Zealand. Because when it's summer here, it's winter in the southern hemisphere. Why does the flu always strike in winter?

Scientists call flu "influenza." That comes from the Italian influenza di freddo, 'the influence of the cold'. That is why concerned parents impress on their children in the winter that they are only allowed to leave the house with a coat and a scarf. But it's not the cold that makes you sick, it's a flu virus. Apparently infected you are more likely when it is cold than in hot weather.

But why is that so?

Flu is in the air

Before you are infected, the virus must first make a trip. Starting point: an infected human. Destination: the unsuspecting passer-by. That sounds very simple, but for a virus, traveling is quite a task. A virus cannot move on its own. It is a tiny, dead package of proteins with genetic material, which will hitch a ride with all kinds of substances that come from your body. For example, rotavirus and norovirus travel through the faeces. The flu virus is packaged in tiny water droplets. When you sneeze, you spread it vigorously, and sometimes with a lot of noise. But you also distribute them lavishly without realizing it: when you exhale. The droplets with the virus in them are so small that you can't see them, and they can float through the air for hours. In 2011, the American University of Virginia Tech investigated the concentration of viruses in the air, in airplanes, crèches and a doctor's waiting room. No less than half of the samples were infected with flu viruses. On average, that was 16,000 pieces per cubic meter of air. If you enter a room where a flu patient was earlier that day, you can inhale the flu viruses he has spread. Whether that happens depends very much on the temperature. Microbiologists at the American Mount Sinai School of Medicine used guinea pigs in 2007 to test how that works. They always took a crate with guinea pigs, which they injected with a flu virus, and put it next to a crate with four healthy congeners. At five degrees Celsius, all healthy guinea pigs became infected. When they repeated the experiment at twenty degrees, only one guinea pig got sick. And at thirty degrees, the healthy guinea pigs remained as fit as a fiddle.

Cold gives wings

Why is that? This has to do with humidity. You might expect viruses to thrive in humid and warm conditions, as germs are less likely to grow in the refrigerator. But viruses can spread much faster when it is cold and dry. Cold air contains less moisture than warm air. When the guinea pigs exhale droplets with the flu virus into dry, cold air, those droplets partly evaporate. This makes the droplet small enough to float and simply blows to the guinea pig in the crate next to it.

[Impression of how an immune cell (left) makes small antibodies that want to clear the flu virus (the three balls on the right).]

You can also contract a virus if it is on an object. Especially on smooth material, such as wood, plastic and metal, a flu virus remains present for a long time. That is why a door handle is such a notorious infected spot. If you grab it and then wipe your hand along your mouth or nose, a virus can also enter your body. But first it has to pass two barriers.

Nose works poorly

It is no fun that more viruses fly through the air in cold and dry weather. But you are doubly unlucky: in cold and dry, the blood vessels in your nose are less perfused and the cilia in your nose work less well. Flu viruses can then enter your body more easily. Once flu viruses have penetrated your body, you still have your immune system. Does that perhaps also work worse in the winter? For a long time, scientists thought so. This would be due to vitamin D, which you need for a well-functioning immune system. And because your body produces vitamin D under the influence of the sun, you have more of it in the summer than during the winter. But in a 2016 study by the Radboudumc in Nijmegen, there was no link between the vitamin D level and the production of six different cytokines: signaling substances that the immune cells produce and communicate between those cells.

Help, a virus!

More interesting are the cytokines themselves. In the Nijmegen study, blood samples were collected from 534 healthy subjects over the course of a year. The blood was exposed to various bacteria, fungi and viruses to measure the immune response. 'As soon as the cytokines see an intruder, they start communicating with other cells,' explains physician researcher Marlies Noz of Radboudumc. 'Occasionally their message is very specific. For example: 'Help, I see a virus, now it's important to produce the right types of white blood cells.' This reaction works not only in the body, but also when the blood is in a test tube. The study found that three major cytokines are produced more strongly in the summer than in the rest of the year. There was a strong seasonal difference, especially in the immune response to flu. According to the Nijmegen researchers, the winter blues in the immune system are one of the possible explanations for the annual flu peak in the cold months.

Why does the immune response work worse when the 'R' is in the month? Because it's so cold and dark outside? Or because you always cool down a bit when you have to go through the cold? Radboud researchers tried to find out last summer during the Lowlands Festival. They had about 200 festival visitors step into a 16-degree bath. They took blood samples before and afterwards. They added flu viruses to the blood, after which they examined the production of cytokines. That cold bath was not for fun. 'If you step into that, you really sacrifice yourself for science,' Noz laughs. 'With the pool, we want to simulate winter cold. We want to know if you are more likely to get the flu if you walk outside in the winter without a coat and scarf, or if you cycle through a shower of rain. That says something about the acute effect of cold on your immune system against the flu. Scientists still know very little about that.'

The Spanish flu swept the whole world in 1918.

We do not yet know the outcome of the Lowlands test. The results will be published in the course of 2018. But it will only take our understanding of our resistance a small step further, because the immune system is dizzyingly complex. Jaap van Dissel, professor of internal medicine and head of infectious disease control at RIVM, is not yet convinced of the seasonal influence on the signalling substances in your immune system: 'If the immune response of cytokines does indeed work less well in winter, you would also expect a peak in diseases such as urinary tract infections and legionella. Those peaks are missing.'

School is a hotbed

But that low humidity and temperature cause winter flu waves is also clear to Van Dissel. He mentions another cause: in winter you sit inside all day with the windows closed and on top of each other. That may sound strange, because in many office buildings windows cannot be opened even in the summer. Yet we lack fresh air, especially in winter. 'Schools are the biggest hotspot for flu transmission,' says Van Dissel: 'Especially if there is little ventilation in winter, the children become infected. And they infect their parents again.'

Then the Italians were right centuries ago with their 'influence of cold'. You get the flu under the influence of cold. Viruses are then more likely to reach you, they penetrate through your nose more easily and they may also have less trouble evading your immune system. Of course, you can try to get ahead of the flu by flying to Australia in the fall and not returning to Europe until six months later. But if you can't afford that, just put on a coat and a scarf. This way you reduce the chance of catching the flu. And then you don't pass on the virus either. 7

Puncture before the wave

An advantage of flu as a seasonal illness is that you can hand out the flu shot at a fixed time. The RIVM advises getting the flu shot between mid-October and mid-November. 'Then you are in time for the biggest peak of the year, because the vaccine needs two to three weeks to evoke antibodies,' says Jaap van Dissel of the RIVM. The flu shot is for anyone with an increased risk of flu: people over sixty and people with, for example, heart or lung disease or who have diabetes. If you already have health problems, the flu can give you unpleasant complications, such as pneumonia. It is very difficult to predict exactly which flu viruses will strike this year. 'We are looking at the viruses that were previously in southern countries such as Australia and New Zealand,' says Van Dissel. 'That says something about the likelihood that a certain flu virus will emerge in our country. In this way, we are trying to discover exactly how the vaccine should be composed.'

'Schools are the big hotspots for the transmission of flu'

Jaap van Dissel, 2018

Flu facts

• According to the RIVM, half a million Dutch people had the flu in the flu season of 2016-2017. Less than half went to the GP with it.
• It is difficult to determine how often the flu leads to serious complications. In any case, about 6500 people ended up in hospital with complications from the flu.
• During the flu epidemic, which lasted from November 2016 to March 2017, 7500 more people died than usual. According to the RIVM, a large part of this can probably be linked to the flu. The flu and its complications are especially fatal if you already have very poor health.
• The deadliest flu pandemic in history was the Spanish flu. About fifty million died from it between 1918 and 1920. The flu claimed more than twice as many lives as the First World War, which ended in 1918. The flu struck mainly among people in their twenties and thirties. They had been exposed to flu viruses from a completely different group in their youth. As a result, their natural resistance did not work well against the Spanish flu.

Do you have the flu or did you just catch a cold?

Flu and colds are very similar. Both are caused by a virus, both are mainly found in the cold months, both can give you a fever and/or a sore throat and/or a stuffy nose. With the flu you can be busy for a week or more. And it can develop into more persistent diseases, such as pneumonia. Another illness that is often confused with the flu is stomach flu. Actually, that's not the flu at all: you are not infected by flu viruses, but by enteroviruses or noroviruses. These spread through faeces or vomit. The best tip against the spread of stomach flu: wash your hands well after going to the toilet. Expensive disease

Flu, or something else?

You might not say it, but the flu is one of the most expensive diseases in the Netherlands. Every year, 13 percent of Dutch employees stay at home for one or more days with the flu. The flu victims are sick for an average of five days. In total, about 4.4 million working days are lost. This costs employers 1.1 billion euros on an annual basis. With that money you can buy the Brazilian Neymar, the most expensive footballer in the world, five times. You can also purchase about thirteen F-35 fighter jets (the Joint Strike Fighter).