Scientists are beginning to untangle one of the most complex biological mysteries of the coronavirus pandemic: Why do some people get severely sick, whereas others quickly recover?
In certain patients, according to a flurry of recent studies, the virus appears to make the immune system go haywire.
Unable to marshal the right cells and molecules to fight off the invader, the bodies of the infected instead launch an entire arsenal of weapons — a misguided barrage that can wreak havoc on healthy tissues, experts said.
“We are seeing some crazy things coming up at various stages of infection,” said Akiko Iwasaki, an immunologist at Yale University who led one of the new studies.
Researchers studying these unusual responses are finding patterns that
distinguish patients on the path to recovery from those who fare far worse.
Insights gleaned from the data might help
tailor treatments to individuals, easing symptoms or perhaps even
vanquishing the virus before it has a chance to push
the immune system too far.
“A lot of these data are telling us that we need to be acting pretty early in this process,” said John Wherry, an immunologist at the University of Pennsylvania who recently published a study of these telltale immune signatures. As more findings come out, researchers may be able to begin testing the idea that “we can change the trajectory of disease,” he said.
When a more familiar respiratory infection, like a flu virus, tries to gain a foothold in the body, the immune response launches a defense in two orchestrated acts.
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First, a cavalry of fast-acting fighters flocks to the site of infection and tries to corral the invader, buying the rest of the immune system time to mount a more tailored attack.
Much of the early response depends on signaling molecules called cytokines that are produced in response to a virus.
Like microscopic alarms, cytokines can mobilize reinforcements from elsewhere in the body, triggering a round of inflammation. -
Eventually, these cells and molecules leading the initial charge will stand down, making way for antibodies and T cells — specialized assassins built to home in on the virus and the cells it has infected.
But this coordinated handoff seems to break down in people with severe Covid-19.
Rather than bowing out gracefully, the cytokines that drive the first surge never stop sounding the alarm, even after antibodies and T cells arrive on the scene. That means the wildfire response of inflammation may never get snuffed out, even when it’s no longer needed.
“It’s normal to develop inflammation during a viral infection,” said
Catherine Blish, a viral immunologist at Stanford University.
“The problem comes when you can’t resolve it.”
This sustained signaling may result in part from the body’s inability to keep the virus in check, Dr. Iwasaki said. Many who struggle to recover from their illness seem to harbor the pathogen long after other patients have purged it, perhaps goading the immune system into prolonging its frantic inflammatory siege.
Plenty of other viruses, including those that cause AIDS and herpes, have evolved tricks to elude the immune system. Recent evidence hints that the new coronavirus might have a way of delaying or muffling interferon, one of the earliest cytokine defenses the body mounts.
The failure of this first line of defense may dupe the immune system into sounding its alarm bells even louder, dragging out the response into something destructive. “It’s an enigma,” said Avery August, an immunologist at Cornell University. “You have this raging immune response, but the virus continues to replicate.”
And the quality of these cytokines may
matter as much as the quantity.
In a paper
published last week in Nature, Dr. Iwasaki and her colleagues showed
that patients with severe Covid-19 appear to be churning out signals that
are better suited to subduing pathogens that aren’t
viruses.