Using a model of airway tissue created from human stem cells, University of California researchers have identified how cigarette smoking causes more severe infection with SARS-CoV-2, the virus that causes COVID-19, in the airways of the lungs.
The study, led by scientists at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at the University of California, and published in Stem cell cellsIn this article, it will help researchers better understand the risks of COVID-19 for smokers and can help develop new treatment strategies to help reduce smokers’ chances of developing serious illnesses.
Cigarette smoking is one of the most common causes of lung disease, including lung cancer and chronic obstructive pulmonary disease, and most demographic studies of COVID-19 patients have indicated that current smokers are at increased risk of severe infection and death. But the reasons for this were not entirely clear.
To help understand how smoking affects SARS-CoV-2 infection at the cellular and molecular level, Dr Brigitte Gomberts partnered with co-lead authors Faithilengaraja Aromogaswamy, Associate Professor of Molecular Pharmacology and Medicine, and Kathryn Plath, professor of biochemistry, to recreate what happens when infected Airways of a Current Smoker with SARS-CoV-2.
The team used a platform known as air-fluid interface culture, which has grown from human airway stem cells and closely replicates how the airways behave and function in humans. The air passages, which carry the air inhaled from the nose and mouth to the lungs, are the body’s first line of defense against airborne pathogens such as viruses, bacteria and smoke.
“Our model replicates the upper part of the airways, which is the first place the virus hits,” said Gomperts, professor of pulmonology and a member of the UCLA Jonsson Comprehensive Cancer Center. “This is the part that produces mucus to trap viruses, bacteria and toxins and contains cells with finger-like bumps that overcome this mucus and leave the body.”
The air-liquid interaction cultures used in the study were cultured from airway stem cells taken from the lungs of five donors with young, healthy, non-smokeless tissue. To replicate the effects of smoking, researchers exposed these airway cultures to cigarette smoke for three minutes daily over the course of four days.
Said Gomperts, who also serves as vice chair for research in pediatric hematology and oncology at the Institute for Children’s Discovery and Innovation at the University of California, Los Angeles.
Then, the group infected cultures that were exposed to cigarette smoke – as well as similar cultures that were not exposed – with live SARS-CoV-2 and the two groups were compared. In models exposed to smoke, the researchers saw between two and three times as much affected cells.
For further research, the researchers determined that smoking led to more severe SARS-CoV-2 infection, at least in part, by blocking the activity of immune system proteins called interferons. Interferons play an important role in the body’s early immune response by stimulating infected cells to produce proteins to attack the virus, calling in additional support from the immune system, and alerting uninfected cells to prepare to fight the virus. Cigarette smoke has been known to reduce the response to interferon in the airways.
“If you think of the airways as the tall walls that protect a castle, smoking cigarettes is like poking holes in these walls,” Gumperts said. “Smoking reduces the natural defenses and this allows the virus to emerge.”
Study co-authors are Arunima Purkayastha, Chandani Sen, and Gustavo Garcia Jr. And Justin Langerman, all from the University of California, Los Angeles.
This work was supported by the National Institutes of Health, University of California Los Angeles Medical Scientist Training Program, University of California School of Medicine David Geffen – COVID-19 Broad Stem Cell Research Center Research Award, California Institute for Regenerative Medicine, and UCLA Clinical and Translational Science Institute (With support from the National Institutes of Health’s National Transitional Science Development Center), the Tobacco-Related Disease Research Program, the Ablon Scholars Program at the UCLA Jonsson Comprehensive Cancer Center and the UCLA Broad Stem Cell Research Center.