Scientists Uncover Biological Signatures of the Worst Covid-19 Cases

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. 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.

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. 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.

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