Thu, May 20, 2021 page9

• The long-term effects of isolation to immunity

  Healthy immune systems work best when exposed to microbes, and long COVID-19 lockdowns might affect people’s resistance to germs

  • By Amelia Tait / The Guardian
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  Every time you kiss a person intimately for 10 seconds, more than 80 million bacteria are transferred from mouth to mouth.

  If you are at a party and double dip your tortilla chip into the salsa three times, about 10,000 bacteria would be transferred from your lips to the dip.

  Say “hi” to your coworkers as you sit down at your office desk and you will be greeted by more than 10 million bacteria on its surface.

  

  Illustration: Mountain People

  Disturbing as these figures might seem, many scientists believe that exposure to these microbes helps fine-tune our immune systems — the network of cells and molecules that protect us from diseases.

  In 1989, David Strachan, an epidemiologist at St George’s Hospital Medical School first proposed the “hygiene hypothesis” — the idea that being too clean causes defects in the immune system, leading to a rise in inflammatory diseases such as asthma and allergies.

  While Strachan’s theory is debated and hygiene saves countless lives, decades of data support the idea that exposure to microbes helps the immune system develop.

  Hang on a minute. For most of the past year, many of us have not been kissing strangers, double dipping at parties or sitting down to work in a crowded office.

  Instead we have been locked up at home by ourselves, sanitizing our hands every time we go to the shop, and holding on to distant memories of restaurants and gyms.

  What has happened to our immune systems during COVID-19 lockdowns? What is to happen now that many countries are opening up again?

  Graham Rook , a microbiologist at University College London, in 2003 proposed an alternative to the hygiene hypothesis.

  Rook’s “old friends hypothesis” posits that as humans evolved, our immune systems learned to cope with the microbes around us in the natural world.

  Rook argues that we need to be exposed to these “old-friend” microbes for our immune systems to develop properly. Strachan’s hygiene hypothesis focused on infections, while Rook’s focuses on more harmless microorganisms.

  “Our immune system is a learning system, just like the brain,” Rook said.

  We are born with an “innate” immune system encoded in our genes, but this is “tuned” by our “adaptive” immune system, which collects data from the microbes around us to determine which are safe and which are dangerous, he said.

  Without the right data, the immune system starts attacking things it should not attack, causing allergies, asthma and autoimmune diseases.

  So first, the good news.

  By the time you are an adult, you have already encountered a whole host of microbes. Your microbiota — the trillions of microbes living on and in you — is “fairly stable and established,” Rook said.

  A year of isolation is thus unlikely to severely damage your immune system’s regulatory mechanisms.

  However, when it comes to children, Rook and other scientists have concerns about the effects of lockdown measures.

  “A child on the 24th floor of a tower block is simply not meeting the appropriate microbiota,” Rook said, adding that staying indoors, away from the natural world and other people, limits the microbes encountered, as does having an unvaried diet, which he fears might be a problem for children going without school meals.

  “It is worrying,” he said.

  Early during global lockdowns, Byram Bridle, an immunologist at the University of Guelph in Canada, was not too concerned for children’s immune development because, after all, children often get stuck at home for a few weeks when they are ill or over the summer holidays.

  “The issue is now, we are over a year and counting,” Bridle said. “We’re talking about a big chunk of development of the immune system. So it’s hard to imagine that this cannot have a negative impact on our children.”

  Like Rook, Bridle worries about a rise in immunological disorders caused by lockdowns limiting children’s exposure to the natural world — even before the COVID-19 pandemic, scientists documented that “those who grow up in large urban centers tend to have a much higher incidence of allergies, asthma and autoimmune diseases.”

  Bridle said that while the immune system does not fully mature until adolescence, birth to age six is the critical period for its development.

  Various studies have posited that problems can arise when infants have limited microbial exposure. It has been shown that children born by caesarean section are exposed to less of their mother’s microbiota than others — they are also statistically more likely to have allergies and inflammatory diseases.

  A 2014 study from the University of Pennsylvania and Bloomberg School of Public Health found that children who are given repeated courses of antibiotics early in life face a greater risk of obesity. The researchers theorized that the medicine killed the good bacteria in the children’s guts.

  Rook said that as well as allergies and autoimmune diseases, poor immunoregulation can cause chronic inflammation, which can lead to diabetes, obesity and cardiovascular diseases.

  “It’s a pretty impressive list,” he said.

  Let us take a moment to press the big “do not panic” button in our brains. While children’s microbial exposure might have been limited by lockdowns, it remains to be seen just how much.

  As countries around the world have been in and out of lockdowns, many of us have not been isolated for an entire year.

  Many children might also have been outside more than usual — one global analysis in the Journal of Forestry Research found that lockdown restrictions correlated with more visits to parks.

  There has also been a boom in dog purchases over the past year, and studies have shown that children who grow up with dogs have a lower risk of developing autoimmune diseases.

  Then there is the fact that microbial exposure is not everything: Our immune response is also determined by our genes.

  Sheena Cruickshank, an immunologist at the University of Manchester, is more optimistic than Rook and Bridle.

  “With the best will in the world, how super-duper clean are kids?” she said.

  Cruickshank said that research about our immune systems is continually ongoing.

  Referring to Strachan and Rook, she said that “both of them could be partially right, both of them could be partially wrong. It’s something that we’re very much investigating.”

  Bridle stresses that while his concerns are based on “sound scientific principles,” they remain speculation.

  “We won’t know for sure until we actually see how all this plays out,” he said.

  It might yet be a few years before we know whether the children of lockdowns have higher rates of immunological disorders.

  “It takes about five years for asthma to really kick in,” said Brett Finlay, a coauthor of Let Them Eat Dirt: How Microbes Can Make Your Child Healthier.

  “The data is not there yet — it’s too early — but we’re imploring people to look,” he said. “We’ve really changed the world we live in, and every time we change the world, we change the microbes.”

  Immunological disorders are one thing, but what about viral infections?

  Many of us — adults and children — have not so much as sniffled for an entire year.

  Does this mean that our immune systems are to be ill-equipped to deal with viruses as the world opens up?

  When it comes to the common cold, Cruickshank said that we do not have too much to worry about.

  “We don’t really build up a long-term resistance,” she said. “We’ve got an advantage coming out of lockdown now, because we’re going into the warmer seasons and that typically means people are outside more — colds do better in small, enclosed spaces.”

  In October and November last year, schools in Hong Kong reopened after a three-month closure, and a large number of common cold outbreaks were reported.

  Ron Eccles, founder of the Common Cold Centre at Cardiff University, said that such outbreaks are to be expected when children crowd together after being apart, but added that “there’s very little to indicate that just because you’ve not had a cold for a while, the next one you get is going to be more severe.”

  Yet when it comes to the flu, Bridle has concerns.

  In January, data from the Royal College of General Practitioners in London revealed that flu rates had plummeted to a 130-year low.

  Researchers argued that travel bans, social distancing and hand washing helped stop the spread.

  While this might sound like good news, Bridle said that it puts us on the back foot when it comes to the next flu season.

  “We deal with the flu virus on an annual basis because it mutates rapidly,” he said. “From year to year, we’re actually dealing with fundamentally different variants.”

  This means that flu vaccinations are also constantly changing — every year, scientists base the vaccine on the predominance of variants spreading the year before.

  “We will potentially be dealing with vaccines that are based on variants that were circulating two years ago instead of one,” Bridle said, adding that our immune responses would also be a year out of date.

  “Our immune systems and the vaccines that we’re using are going to be targeting a virus that has now been able to accumulate two times the mutations than what we would normally be facing,” he said.

  Although there is a counterargument that with so little flu virus in circulation, it would have had less chance to mutate, and therefore using last year’s formulations is an acceptable strategy.

  Nevertheless, Bridle said that this is most concerning for “the two ends of the spectrum” — the elderly and the very young.

  Rook also has concerns that limited microbial exposure could affect the elderly.

  Although there is little evidence that having a less-diverse microbiota means that you are more susceptible to viruses, the kind of isolation induced by lockdowns that affects microbial exposure could have knock-on effects in terms of bacterial infections that might otherwise have been less of a problem.

  A 2012 article in Nature found that the gut microbiota of people in long-term care was less diverse than those out in the community, saying that “loss of community-associated microbiota correlated with increased frailty.”

  Younger and middle-aged adults are not totally off the hook — while they are not at the highest risk for flu complications, there is evidence that loneliness and stress can weaken the immune system.

  So, what on earth should we do?

  Rook said that children should continue to be exposed to the natural environment and “run around in the park as often as possible.”

  Finlay advised to “think from a microbial exposure point of view” — go outside, hug a dog, and also eat fruit, nuts, legumes and “all the stuff your mum tells you to eat,” as nutrition is crucial for a healthy immune system.

  Cruickshank said that the immune system can also be mobilized by moderate exercise.

  Crucially, do not be misled into throwing away your disinfectant — lack of hygiene does not lead to better immunological development, and it is important to continue to keep clean to ward off harmful pathogens, she said.

  Finally, Rook also stresses that it is imperative to keep up to date with your child’s vaccination schedule.

  “Not only do vaccines stop you from getting the infection that they are targeting, they also help with the training of the immune system in a nonspecific way,” he said.

  However, many questions remain.

  “Our innate and adaptive immune system will develop regardless of whether we are exposed to the microbial world or not,” Bridle said. “The question is: Will they develop appropriately?”

  Personally, he is concerned.

  “In some of our children as a result of this excessive isolation, we are likely causing irreparable harm. It’s frustrating as a scientist when you consider this in the context of children being at an extremely low risk from the Sars-CoV-2,” he said.

  The data is not yet here — it is too early to see the lasting effects of lockdowns.

  Finlay hopes that scientists would use this opportunity to learn more about microbial exposure.

  “Here’s, I think, one of the biggest experiments we’ve ever been able to do with humanity — we’ve got the whole globe involved,” he said. “Let’s make use of this opportunity and characterize the microbes over time and follow these things. Let’s see what happens to us because it’s really an experiment that’s happening right now.”
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