BU researchers say they found what causes fatal lung inflammation in COVID-19 patients

Lung tissue grown from stem cells provides model for studying COVID-19 infection

BOSTON — Among a sea of symptoms in patients with COVID-19 is severe inflammation of the lungs, leading to decreased lung function, the need for a ventilator and possibly even death.

COVID-19, a variation of acute respiratory infections, wreaks havoc on the respiratory system by attacking lung cells and suppressing the body’s immune response, according to new data from Boston University researchers.

Using lung tissue developed by human stem cells, which were originally used to study the effects of smoking on the lungs, doctors at the Boston University Center for Regenerative Medicine (CReM) and National Emerging Infections Diseases Laboratories (NEIDL) have uncovered the process that COVID-19 uses to erode lung function in infected patients.

The virus initially prevents the lung cells from calling for help from the immune system by stopping proteins called interferons, the team said.

“Our data confirms that SARS-CoV-2 blocks cells from activating one of the anti-viral branches of the immune system early on after infection has set in. The signal the cells would typically send out, a tiny protein called interferon that they exude under threat of disease, are instead delayed for several days, giving SARS-CoV-2 plenty of time to spread and kill cells, triggering a buildup of dead cell debris and other inflammation,” explains study author Dr. Darrell Kotton.

By the time the immune system can respond to the virus, the lung tissue is already riddled with infected or dead and dying cells.

The research team, led by co-first authors, Jessie Huang, PhD, Kristy Abo, BA, Rhiannon Werder, PhD and Adam Hume, PhD, adapted an experimental model previously used to study the effects of smoking cigarettes to study the coronavirus in lung tissue. Droplets of live coronavirus were then added on top of the lung cells, infecting them from the air the way the virus infects cells lining the inside of the lungs when air containing the virus is breathed into the body.

—  BU press release

Two of the study’s authors are also pulmonary and critical care physicians taking care of patients with COVID-19 pneumonia at Boston Medical Center

"Members of the CReM have developed sophisticated models of human lung tissue—three-dimensional structures of lung cells, called “lung organoids,” grown from human stem cells—which they’ve used at BU and with collaborators elsewhere to study a range of chronic and acute lung diseases," a Boston University release stated.

The team’s findings appear online in the journal Cell Stem Cell.

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