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Immune system culprit in severe COVID cases found

Yale researchers have identified a particular immune response pathway that leads to severe illness and death in people infected by the SARS-CoV-2 virus.

Researchers have known that once the COVID-19 virus infects the lungs it can trigger what has been called a “cytokine storm,” or an overactive immune response that leads to deadly inflammation in the lungs. For the new study, a Yale team led by postdoctoral fellow Esen Sefik, who is part of the lab of senior author Richard Flavell, studied the effects of SARS-CoV-2 infection in mice engineered to have a human immune system.

To their surprise, they found that immune cells themselves, not just epithelial cells lining the lung, can harbor the virus. When the body detects the virus in these cells, inflammasomes, part of the immune system’s early warning system, produce and release cytokines which prompt these immune cells to 'commit suicide' in an attempt to abort infection. However, the cytokines also recruit even more inflammatory cells to the lungs from the blood, which drives a vicious cycle that leads to pneumonia.

“It’s like a broadcast system, but in this case the message is lethal,” said Flavell, Sterling Professor of Immunobiology and investigator for the Howard Hughes Medical Institute.

In the mouse model of COVID-19, researchers were able to rescue infected mice from pneumonia by blocking the NLPR3 inflammasome pathway. With the inflammasome pathway blocked, immune system cells were still infected. But they were no longer inflammatory and therefore could not contribute to damaging levels of inflammation, researchers found.

One byproduct of this rescue, however, is that the cells no longer die and, as a consequence, release more virus. Nonetheless, blockade of the inflammasome pathway along with antiviral treatment could provide a way to treat COVID-19 pneumonia and prevent severe cases of COVID -19, researchers say. Although there are no approved drugs that block the NLPR3 pathway, several pharmaceutical and biotech companies are developing them, Flavell said.

The research was funded by the Howard Hughes Medical Institute and published April 28 in the journal Nature.

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Upcoming Events

AfPP Annual Conference 2022

University of York
8-11 September 2022

Infection 360: What's trending in infection prevention & control

Edgbaston Stadium, Birmingham
27-28 September 2022

IP2022 IS COMING TO BOURNEMOUTH IN OCTOBER 2022

Bournemouth
17-19 October 2022

UKHCA Conference: Listen Up

Pendulum Hotel and Manchester Conference Centre, Manchester
3rd November 2022

MEDICA 2022

Dusseldorf Germany
14th November - 17th November

Future Surgery 2022

ExCel, London
15th - 16th November 2022

Access the latest issue of Clinical Services Journal on your mobile device together with an archive of back issues.

Download the FREE Clinical Services Journal app from your device's App store

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