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Why obesity makes Covid-19 more dangerous - and what you can do to survive



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Obesity researcher Stephen O’Rahilly is living proof of the subject of his upcoming talk.

At the Cambridge Festival, he will discuss why people living with obesity are facing far worse off when they catch Covid-19 than their leaner friends and family - but how even losing small amounts of weight could make a huge difference to their survival chances.

A growing body of evidence indicates that obesity is strongly and independently associated with adverse outcomes from catching the coronavirus. There have been attempts to explain this based on the physical effects of obesity.

But Professor O’Rahilly, from the Wellcome-MRC Institute of Metabolic Science, suggests that we look closely into the metabolic effects to move the science forward and pinpoint effective medical interventions.

Prof Sir Stephen O’Rahilly - obesity expert Head of the University Department of Clinical Biochemistry on his talk for cambridge Festival . Picture: Keith Heppell. (45172780)
Prof Sir Stephen O’Rahilly - obesity expert Head of the University Department of Clinical Biochemistry on his talk for cambridge Festival . Picture: Keith Heppell. (45172780)

He believes a diet in the early months of 2020, in which he shed around 10kg, may have meant the difference between life and death for him when he was hospitalised with the virus.

Prof O'Rahilly says: “I've been a long-standing obesity researcher and obviously when Covid came along there was a lot of publicity about the fact that people with obesity tended to get more problems with symptoms.

“My talk will look at why that is. The first question I will address if this is a real problem - and the answer is that it is.

“People with obesity don't get infected with the virus any more often than people without obesity, as becomes clear when we look at infection rates.

“But when people get Covid-19 there is a clear relationship between how obese people are and whether they end up on ITU or even they end up dying. And it’s a strong and pretty linear relationship.

“The work that I have been involved with that's hopefully going to be published soon, working with people in Oxford, has shown that the relationship stretches right across from overweight categories into obese and goes up and up. So it's very clear that the body mass index has a real effect and obese adults have worse outcomes from Covid-19 than lean people.”

In fact, obese patients suffer far more with Covid-19 than they do with other respiratory illnesses.

Prof O'Rahilly says: “The second question I will ask is whether obese people have worse outcomes with any bad lung infection, and the answer is no; it's not true.

“People might think that if someone has a big heavy chest or is fat in the tummy that makes it harder to breathe and that’s why obese people might suffer worse with Covid-19. They think very mechanically about obesity.

“But it is not true of regular influenza or when people have bad lung damage from septicemia or post-operative lung damage or car crashes - people don't do worse in those circumstances if they are obese. In fact, under some of those circumstances carrying a bit of extra fat helps you. So, there is something very special about the relationship of obesity with Covid.”

Inflammation and clotting

Two factors appear to be making Covid-19 outcomes worse for obese patients - inflammation and blood clotting.

“Obesity it isn't just a mechanical condition. It is associated with a huge range of chemical changes in the body,” says Prof Rahilly.

“And those chemical changes can have profound impacts on the processes that lead to to lung damage in Covid-19, such as for example the tiny thromboses that are very typical of Covid damage, caused by having multiple small clots. That's very different from people dying from flu, for example. It's a different pathology. Clotting is a really big part of the Covid lung damage; we know so much about how the over-nourished state can promote clotting and stop us from breaking down clots.

“And then when you have lots of fat tissue you tend to have lots of inflammatory cytokines too, which make us inflamed. The lungs of people with Covid are very inflamed.”

Two drugs which have been shown to increase survival chances for patients hospitalised with Covid-19 both work on inflammation. One is dexamethasone, which is a corticosteroid used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects; the other is arthritis drug Tocilizumab, also known as atlizumab, an immunosuppressive drug.

Prof Sir Stephen O’Rahilly - obesity expert Head of the University Department of Clinical Biochemistry on his talk for cambridge Festival . Picture: Keith Heppell. (45172775)
Prof Sir Stephen O’Rahilly - obesity expert Head of the University Department of Clinical Biochemistry on his talk for cambridge Festival . Picture: Keith Heppell. (45172775)

Prof O'Rahilly says: “These drugs work, not by getting rid of the virus, but by bring down the inflammation. So inflammation is clearly playing a role in a patient’s own body's attempt to get rid of a virus and that's probably what kills us. Obesity is likely to be worsening that aspect of the viral path.

“Even though we haven't proved all of this yet, it's a useful public health message. If you imagine that obesity is like an iceberg you have the tip of the iceberg where you have all the problems of diabetes and liver fat, and under the water are lots of chemical changes that nobody sees but they are there - and that’s making the Covid worse.”

Small weight losses improve body chemistry quickly

The good news for anyone who struggles to lose weight is that, according to Prof Rahilly, you don’t have to lose all of your excess pounds to bring down your Covid risk.

He explains: “A nice thing is that those chemical changes can improve really quite quickly. You don't have to lose stones and stones to start putting those chemical changes right. In fact, as soon as you start losing weight many of those chemical changes start getting better before you even change your belt size.”

So a small weight loss could improve an obese person’s chances of surviving Covid-19 almost immediately?

“It happens essentially because when you go into negative energy balance, in other words, when you start expending more energy than you bring in - which is what happens when you're losing weight - one of the first places that the fat disappears from is not your fat cells," says Stephen.

"It disappears from your inner organs like your liver and your muscle. You get a significant reduction in those first and that's probably where the fat is causing the problem.

“One place where the fat isn't causing a problem is your love handles. Fat causes a problem when it is in places where it shouldn't be, such as in muscle and liver so by starting to lose weight you lose fat from those places and have a disproportionate impact on your inner health before you see much in the way of weight loss.

Even losing a small amount of weight can help improve Covid-19 outcomes
Even losing a small amount of weight can help improve Covid-19 outcomes

“From everything we know about, for example, fat in the liver and the levels of insulin in the blood - if you restrict calories for 48 hours you improve those features quite quickly. We know how rapidly metabolic features improve when you lose weight and there's definitely benefit to be had from losing small amounts.

“Some people may have been trying to lose a significant amount of weight for years and just find it impossible. But if you lose a pound or walk a mile, both things are likely to improve the chemistry. You don’t need to set unrealistic goals of going from 20 stone to 10 stone in six months. Don't despair - by all means losing loads of weight is better, but even losing a bit helps.”

Prof O’Rahilly believes that losing a moderate amount of weight just before he caught Covid-19 may have saved his life.

“ I have always been heavy,” he says.

“But I lost about nine or 10 kilos before Covid came. When I caught the virus, I did end up in hospital but I didn't end up in ITU. I think possibly that made the difference. I'm a scientist and I can't prove that, but I wouldn't be surprised if that more than a stone I lost in the few months coming up to Covid-19 saved my life.

"I wouldn't want to be that sick again. It was one of the sickest I've ever been, but fortunately I didn't have to go into intensive care.”

Obesity is not a failure of willpower

One of Professor O'Rahilly’s bugbears is that people still stubbornly believe that willpower is the answer to being slim. He is adamant that willpower is nothing to do with it.

“People who are overweight or obese simply feel hungrier than leaner people. It's by far the biggest reason that people become obese. All the genetics points to this area of the brain called the hypothalamus, which controls appetite. Every time you find a broken gene in severely obese children every time you find a common genetic variant that predisposes to obesity in the population, you find that these people generally are hungrier and they eat more and are less satiated by food. It's terrible.

“People don't like to think that's the case. They say it must be their willpower that is lacking but it's nothing to do with that. I tell my lean colleagues I can see you skipping lunch some days. I would no more skip lunch than cut my foot off! I couldn't work if I didn't have my lunch. I would be too hungry. I have worked with and lived with naturally lean people and they find it extremely easy to miss meals it and it's not a problem for them. I'm different. It doesn't mean I'm worse.

“People would prefer to think that they burn off calories slower and that's why they put on weight and maybe there's a tiny bit of that, but it's mostly biological differences in appetite, which are nothing to do with how clever you are, how nice you are, how fun you are. It's just to do with random variations in your hypothalamus.

“There is no evidence that obese people lack willpower in other aspects of their lives. The parts of the brain that control appetite are very primitive and the bits that do all the decisions about whether you're going to work hard, be a good employee, be a good parent, are all in different parts of your brain and bear little or no relationship to obesity, so I think it's nonsense.”

Diets are therefore extremely difficult for those genetically predisposed to eat more.

Prof O'Rahilly says: “If you want to lose weight by dieting, the few people who are successful long-term dieters really have to be utterly obsessional. They can never let it go because their basic brain is telling them something different than their thinking brain.”

New weight loss drugs that work - and are safe

However, it’s not all doom and gloom for those trying to restart yet another diet. There are some effective obesity drugs on the horizon that work to reduce appetite to more normal levels, and they are safe.

The drug Semaglutide, which has been used in low doses to treat type 2 diabetes has been found to reduce appetite and can cause patients to lose up to 15 per cent of their body weight. This class of drugs is commonly called glucagon-like peptide 1 (GLP-1) agonists.

Already available on private prescription in the UK, the injection may soon be approved by the NHS to treat obesity.

Prof O’Rahilly says: “They have been used for over 10 years on millions of people with type 2 diabetes around the world and the evidence is that people who are using it die less frequently not more frequently

“It's like partial bariatric surgery in a pill and it will be safe. I don't know whether it will be approved by the NHS, as obesity has such a bad press in this country. Everyone assumes this is all down to individual will, not down to biology, and that it is people's own fault, all of which is untrue. It will be hard to break that cycle of thinking.”

The drugs work by by binding to GLP-1 receptors and stimulate insulin release from the pancreas to help reduce blood sugar levels. They also help to reduce the amount of sugar released by their liver and slow down food leaving the stomach, to help prevent blood sugar spikes.

Prof Sir Stephen O’Rahilly - obesity expert Head of the University Department of Clinical Biochemistry on his talk for cambridge Festival . Picture: Keith Heppell. (45172780)
Prof Sir Stephen O’Rahilly - obesity expert Head of the University Department of Clinical Biochemistry on his talk for cambridge Festival . Picture: Keith Heppell. (45172780)

“It's very effective if you can tolerate the nausea, which can be an issue, although not that many people have to come off because of the side effects,” he says.

“It reduces your appetite, nothing else. It just makes you want to eat small of meals and feel less hungry and even when you lose weight it just keeps working. When you go on a diet and lose weight your body has a natural tendency to find its way back to your original weight. But this drug stops that while you continue to take it.”

He hopes that the way we treat obesity will changes.

“My hope is that we gradually mature as a society and start thinking about obesity like we thought about high blood pressure 50 years ago. With high blood pressure, you need to reduce the salt in the public diet and you need to screen people for high blood pressure and you need to use sensible pharmacology drugs

“We have no problem now with people being on two or three drugs to control their blood pressure and not have strokes and we have done that dramatically well. When I was a young doctor, the world was full of people with terrible complications from high blood pressure and now you never see it. We fixed that by having a sensible attitude towards people who happen to have high blood pressure we need to just start shifting the thoughts about obesity.”

You can listen to Prof O'Rahilly's talk at the Cambridge Festival by signing up here: https://www.festival.cam.ac.uk/events/why-does-obesity-make-covid-19-more-dangerous.

There are more than 350 events at the Cambridge Festival, organised by the University of Cambridge and supported by the Cambridge Independent. The festival runs from March 26-April 4. Visit festival.cam.ac.uk to browse events and book your places.



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