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Researchers wrestle with fierce flu

It’s a well-known fact that the old and the sick are particularly susceptible to influenza. But why does the flu cause such havoc in apparently fit and healthy people that they – even the young – can die from it?

This question has been puzzling medical science for many years, and eight researchers from Aarhus University, funded by the Danish Council for Independent Research and the Lundbeck Foundation, are now offering an answer.

Their findings were recently published in the scientific journal Medical Microbiology and Immunology. In their article, the Aarhus scientists suggest that, in certain cases, the explanation could be a genetic variant which basically creates a kind of hole in the immune system, making otherwise fit and healthy people extremely vulnerable to certain types of influenza.

The article is based on a DNA study of blood samples taken from 12 former patients who were admitted to Aarhus University Hospital’s intensive care unit suffering from influenza H1N1. All were otherwise healthy – and some of them were young – but all had become life-threateningly ill from H1N1, a super-strength influenza also known as swine flu.

The blood samples were taken in 2016, when H1N1 was past history for these 12 people. Fortunately, they had all survived and were now happy to help medical science. And the samples had a clear purpose.

Trine Mogensen, doctor and professor at the Department of Infectious Diseases at the university hospital and the Department of Biomedicine, explains that the aim was to investigate whether they could identify something in the DNA of these patients which could clarify why H1N1 made them so very ill.

‘We examined the blood samples of the 12 former patients and fully mapped the DNA of each patient. And we found something interesting,’ says Trine Mogensen, who headed the scientific study.

45-year-old male
One of the samples they studied was taken from a 45-year-old man who was admitted to the university hospital’s ICU with an H1N1 infection in 2010. And it was in this man’s DNA that Professor Mogensen and her colleagues spotted a remarkable genetic variant.

There was a defect in the interferon system – a biological system that uses signal molecules to inform the body to put its immune system on high alert, for instance when it is attacked by a severe virus.

‘P’, as this patient is called in the scientific article, was in no way unhealthy when he contracted swine flu in 2010. Nor was his lifestyle debilitating, making him extra vulnerable to viruses. Trine Mogensen explains:

‘Our hypothesis is that P fell so ill because his genetic make-up prevented activation of his immune system. Metaphorically speaking, there was a breach in his defences.’

According to Professor Mogensen, there is scope in the knowledge gained by the Aarhus researchers from the studies of P’s DNA for several very valuable applications:

‘For one thing, it can improve our understanding of how the human immune system works when we have the flu. We may even be able to use it – somewhere down the line – to develop a test that will help doctors identify people who are genetically particularly vulnerable to certain types of flu and therefore need the best possible protection, for instance in the form of a vaccination.’

Ultimately, the Aarhus researchers hope that this new knowledge will inspire design of new therapies for this patient group, for which mortality can be up to 50% if they reach the stage of admission to an ICU.

Trine Mogensen and her colleagues are currently in the process of identifying other genetic variants able to create holes in the immune system when people who are otherwise fit and healthy contract influenza.

So far, they have identified one further variant, which will soon be published.

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