In Deadly COVID-19 Lung Inflammation, BU Researchers Discover a Culprit in NFkB Pathway

As the coronavirus pandemic ripped through through the United States in March, scientists at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the Center for Regenerative Medicine (CReM) dropped all other research to focus exclusively on the SARS-CoV-2 virus. They joined forces to develop the most relevant research model possible for understanding how the virus impacts the lungs, engineering living, “breathing” human lung cells from stem cells for the task.

Those efforts from early on in the pandemic have borne a leap forward in our understanding of how COVID-19 infections trigger deadly levels of lung inflammation. Their discovery of a pathway that sets the lungs ablaze with inflammation has launched a search for new therapeutics that could block this process before it can take off and turn fatal.

According to their findings, published online last week in Cell Stem Cell, the trouble starts soon after the air sacs in the lungs are infected with SARS-CoV-2, when the virus activates one of the body’s biological pathways known as NFkB (the k is pronounced “kappa”). As that’s happening, the virus also suppresses the lungs’ ability to call in the help of the immune system to fight off the viral invaders.

When the signal for help finally goes out—several days after infection has taken hold—an army of immune cells swarms into lung tissue heavily laden with infected, dead, and dying cells and with unchecked levels of inflammation triggered by the early activation of NFkB. The incoming immune cells, by attempting to destroy every infected cell in their path, add more fuel to the fire. Every infected cell killed by the virus or by immune cells trying to thwart viral spread tips the scales of inflammation closer to sending the lungs and other organs into total failure.