What Sets Off Deadly Levels of Lung Inflammation in Some COVID-19 Patients? (Video)

Original article from The Brink by Kat J. McAlpine & Carlos Soler

A team of infectious disease and regenerative medicine researchers at Boston University, studying human stem cell–derived lung tissue infected with SARS-CoV-2, are discovering new insights into how the novel coronavirus kicks off a cascade of tissue inflammation in the lungs.

That reaction can be especially lethal for older people, who make up 8 out of every 10 deaths from COVID-19, the disease caused by the coronavirus. As people get older, their risk of having an underlying health condition increases, and at the same time, their immune system is aging. Both of those factors are thought to contribute to chronic inflammation—making older people far more susceptible to the added inflammation that a COVID-19 infection sets off in the body.

The researchers’ experimental data appears to confirm a theory developing among clinicians and researchers that SARS-CoV-2 initially suppresses lung cells’ ability to call in the help of the immune system to fight off the viral invaders. The delay in recruiting defensive reinforcements then backfires, the signal going off several days after infection has set in. That delay attracts an army of immune cells into lung tissue laden with infected and already dead and dying cells, dousing those inflammatory conditions with even more fuel.

Like most other scientists racing to find promising new strategies to halt the spread of COVID-19, the BU team has publicly released their data in a “preprint” paper (a draft that has not been formally reviewed and published in a peer-reviewed journal) to share their research with the scientific and medical community as soon as possible while their findings are being peer-reviewed for publication in a scientific journal.

“The data is teaching us that [the cells lining the lungs] act something like a white blood cell,” a patrolling watchdog cell that’s part of the immune system, after infection with SARS-CoV-2, says study coleader Darrell Kotton, a lung biologist and director of the Center for Regenerative Medicine (CReM) on BU’s Medical Campus. The infected lung cells “pour out inflammatory proteins.” In the body of an infected person, those proteins drive up levels of inflammation in the lungs.

The data is based on experiments the research team performed at BU’s National Emerging Infectious Diseases Laboratories (NEIDL). Kotton and other members of 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.

Adapting their expertise to engineer alveolar cells, which line the inside of lungs and are difficult to extract from patients for research purposes, the CReM lung model is being infected with SARS-CoV-2 by virologists at the NEIDL. The stem cell–derived lung model provides a better model of cells found in real human lungs than, as is commonly done, using cultures of animal-derived cells to investigate disease.

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