Researchers discover culprit in deadly COVID-19 lung inflammation

Graphical abstract of findings presenting an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture.
Credit: Jessie Huang et al, Cell Stem Cell.

A team of NHLBI-funded researchers has discovered a biological pathway that triggers deadly levels of lung inflammation when activated by SARS-CoV-2, the coronavirus that causes COVID-19. The findings, published in the journal Cell Stem Cell, have launched a search for new treatments that could block the onset of this process.  

Early on, after the infection has set in, SARS-CoV-2 suppresses the lung cells’ ability to call in the help of the immune system to fight off the viral invaders the scientists found. Instead, the virus activates a pathway that pours out inflammatory proteins, which, in the body of an infected person, drive up the levels of inflammation in the lungs.

When the signal to the immune system goes out, several days later, the virus has had ample time to spread and kill cells, triggering a buildup of dead cell debris and further inflammation. Then, an army of immune cells swarms into lung tissue heavily laden with infected, dead, and dying cells and with unchecked levels of inflammation. As these cells try to do their job and destroy every infected cell in their path, they compound the problem and the inflammation inches ever closer to sending the lungs and other organs into total failure.