rvallee
Senior Member (Voting Rights)
Scientists Uncover Biological Signatures of the Worst Covid-19 Cases
https://www.nytimes.com/2020/08/04/health/coronavirus-immune-system.html
https://www.nytimes.com/2020/08/04/health/coronavirus-immune-system.html
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?
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.
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.
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.
Although the delineations aren’t always clear-cut, the immune system’s responses to pathogens can be roughly grouped into three categories: type 1, which is directed against viruses and certain bacteria that infiltrate our cells; type 2, which fights parasites like worms that don’t invade cells; and type 3, which goes after fungi and bacteria that can survive outside of cells. Each branch uses different cytokines to rouse different subsets of molecular fighters.
People with moderate cases of Covid-19 take what seems like the most sensible approach, concentrating on type 1 responses, Dr. Iwasaki’s team found. Patients struggling to recover, on the other hand, seem to be pouring an unusual number of resources into type 2 and type 3 responses, which is kind of “wacky,” Dr. Iwasaki said. “As far as we know, there is no parasite involved.”
This disorientation also seems to extend into the realm of B cells and T cells — two types of immune fighters that usually need to stay in conversation to coordinate their attacks. Certain types of T cells, for instance, are crucial for coaxing B cells into manufacturing disease-fighting antibodies.
Last month, Dr. Wherry and his colleagues published a paper in Science finding that, in many patients with severe Covid-19, the virus had somehow driven a wedge between these two close-knit cellular communities. It’s too soon to tell for sure, but perhaps something about the coronavirus is preventing B and T cells from “talking to each other,” he said.
Timing is also crucial. Dose a patient too early with a drug that tempers immune signaling, and they may not respond strongly enough; give it too late, and the worst of the damage may have already been done. The same goes for treatments intended to shore up the initial immune response against the coronavirus, like interferon-based therapies, Dr. Blish said. These could stamp out the pathogen if given shortly after infection — or run roughshod over the body if administered after too long of a delay.