Asymptomatic cases are not unique to Covid-19. They occur with the regular flu, and probably also featured in the 1918 pandemic, according to epidemiologist Neil Ferguson of Imperial College London. But scientists aren’t sure why certain people weather Covid-19 unscathed. “ That is a tremendous mystery at this point ,” says Donald Thea, an infectious disease expert at Boston University’s School of Public Health.
These experts are learning that the human body may not always wage an all-out war on viruses and other pathogens. It may also be capable of accommodating an infection, sometimes so seamlessly that no symptoms emerge. This phenomenon, known as disease tolerance , is well-known in plants but has only been documented in animals within the last 15 years.
At least 90 percent of those infected with the tuberculosis bacterium don’t get sick.
“With things like Covid, I think it’s going to be very parallel to TB, where you have this Goldilocks situation,” says Andrew Olive, an immunologist at Michigan State University, “where you need that perfect amount of inflammation to control the virus and not damage the lungs.”
Some of the key disease tolerance mechanisms scientists have identified aim to keep inflammation within that narrow window. For example, immune cells called alveolar macrophages in the lung suppress inflammation once the threat posed by the pathogen diminishes.
Studies show that their lungs often display damage on CT scans , yet they are not struggling for breath (though it remains to be seen whether they will fully escape long-term impacts). Moreover, a small recent study suggests that asymptomatics mount a weaker immune response than the people who get sick — suggesting that mechanisms are at work that have nothing to do with fighting infection.
“Why, if they have these abnormalities, are they healthy?” asks Ayres. “Potentially because they have disease tolerance mechanisms engaged. These are the people we need to study.”
A 2018 experiment in Ayres’ lab offered proof of concept for that goal. The team gave a diarrhea-causing infection to mice in a lethal dose 50 trial, then compared tissue from the mice that died with those that survived, looking for differences. They discovered that the asymptomatic mice had utilized their iron stores to route extra glucose to the hungry bacteria, and that the pacified germs no longer posed a threat. The team subsequently turned this observation into a treatment. In further experiments, they administered iron supplements to the mice and all the animals survived, even when the pathogen dose was upped a thousandfold.