“Why Do Some People Weather Coronavirus Unscathed?”
by Emily Laber-Warren
Undark, August 24, 2020
From Emily Laber-Warren, director of health/science reporting at Newmark J School at CUNY
July 2, 2020
Symptom-free COVID cases may highlight the body’s ability to tolerate infections
COVID-19 is a bizarre Wheel of Fortune game being played involuntarily by everyone on the planet. When it’s your turn to spin, will the wheel stop at pneumonia? Organ failure? Loss of smell and taste? Or will you be among the lucky ones—the vast majority, according to the latest CDC data—who weather the infection with no symptoms at all?
Janelle Ayres, a physiologist and infectious disease expert at the Salk Institute, isn’t surprised by the wide range of responses to the virus. In her lab, she has seen mice perish from an infection that barely ruffles their genetically identical brethren. Ayres studies the factors that enable animals to stay healthy in the presence of a pathogen, and what she is learning could have profound implications for our understanding of infectious disease.
The conventional explanation for why some people sail through COVID unscathed is that their immune systems fight off the virus so seamlessly that they never get sick. Ayres’s research suggests that this may be just part of the story.
What Ayres and a few like-minded colleagues have discovered is that an infection triggers two distinct responses. There’s the well-known immune response, which churns out antibodies and other molecules to fight off the pathogen. But Ayres has identified a second system that works in parallel. This so-called “cooperative defense system” helps organisms tolerate disease—a phenomenon that is well-known in plants, and has more recently been documented in animals.
If you think of the immune system as a military force, the cooperative defense system is a diplomatic corps. It doesn’t aim to kill or even get rid of the pathogen. But sometimes it works even better than the immune system does. The infection isn’t gone, but that doesn’t matter because the infected person feels just fine.
“I think the lesson is that there are things to consider other than what the pathogen brings to the table,” says Ralph Isberg, a professor of microbiology at Tufts University School of Medicine. “It’s crazy that people hadn’t thought about this before.”
Ayres recently published a manifesto of sorts in the prestigious journal Cell that she hopes will jumpstart research into the cooperative defense system. Meanwhile she sees evidence of these mechanisms at work in the COVID-19 pandemic. For example, some asymptomatic patients have COVID-related lung abnormalities that show up on CT scans. These people are physically impaired and should be struggling for breath, but they’re not—suggesting to Ayres that the cooperative defense system has kicked in and is keeping them healthy even as the virus replicates within their cells.
In an April 29 editorial in Science Advances, Ayres urged that more resources be devoted to developing medications that rev the body’s natural defenses. These drugs would not be disease-specific but would instead bolster the health of entire organ systems. For example, Ayres envisions lung-repair medicines that would ease breathing problems related to respiratory distress, regardless of the responsible pathogen. Such broad-based therapies would not replace vaccines and antivirals, but they would come in handy the next time a pandemic arrives out of nowhere, catching scientists off guard. While researchers race to develop a targeted response, doctors would have more than just oxygen and ventilators to offer.
“We need to just change the question oh-so-slightly,” says Ayres, who in the past two years has received two prestigious awards and a $3.5 million NIH grant. “Rather than how do we fight disease, how do we promote health?”
I’m proposing a 1,600-word feature for Undark on how the emerging understanding of disease tolerance could change medicine, if not in time for this pandemic, then for the next. In addition to Ayres and Isberg, I’ve interviewed immunologists Dan Littman at NYU, Douglas Green at St. Jude Children’s Research Hospital and Jeremy Luban of U Mass Medical School, all of whom are enthusiastic but uninvolved observers of this new field of research, along with David Schneider at Stanford and Andrew Read, who have themselves done research in disease tolerance.
I’m a longtime science and health journalist (see my work here) and head of Newmark J school’s health & science reporting program. Thank you for reading and I hope you agree that this emerging field of medicine is fascinating and relevant.