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Smoking Increase the Severity of SARS-CoV-2 Infection

Several identified risk factors are known to raise the risk of serious illness from SARS-CoV-2 infection, such as increased age, obesity and heart problems. Smoking is also associated with an increased risk of extreme COVID-19 at present, but it is unclear how exposure to cigarette smoke affects the infection of SARS-CoV-2 airway cells. UCLA researchers have now established that how smoking cigarettes induces more serious SARS-CoV-2 infection in the airways of the lungs, using a model of airway tissue developed from human stem cells.

The group found that direct exposure to cigarette smoke increases the number of infected SARS-CoV-2 cells, that infection with SARS-CoV-2 inhibits the response of airway basal stem cell repair, and that cigarette smoke decreases innate immune responses to infection with SARS-CoV-2. The data would help researchers better understand the risks to smokers from COVID-19 and may inform the development of new therapeutic methods to help minimise the likelihood of smokers developing serious illnesses.

The study was published in Brief Report in Cell Stem Cell under titled, “Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response.”

One of the most common causes of lung diseases, including lung cancer and chronic obstructive pulmonary disease, is cigarette smoking, and most demographic studies of patients with COVID-19 have shown that current smokers have an elevated risk of serious infection and death. But the reasons why were not fully clear.

Brigitte Gomperts, MD, professor of paediatrics, pulmonary medicine at the Large Stem Cell Research Center at UCLA, collaborated with co-senior authors Vaithilingaraja Arumugaswami, PhD, associate professor of molecular and medical pharmacology, and Kathrin Plath, PhD, professor of biological chemistry, bobo, to better understand how smoking impacts SARS-CoV-2 infection at the cellular and molecular level.

Air-liquid interface cultures derived from primary human non-smoker airway basal stem cells (ABSCs) were directly exposed by the researchers to short-term cigarette smoke and then contaminated with SARS-CoV-2.

The air-liquid interface cultures used in the study were grown from five young fit, nonsmoking tissue donors' airway stem cells taken from the lungs. The researchers subjected these airway cultures to cigarette smoke for three minutes a day for four days in order to replicate the effects of smoking.

Gomperts said, "Our model replicates the upper part of the airway, which is the first place the virus hits." "This is the part that generates mucus to trap viruses, bacteria, and toxins and contains finger-like projections of cells that beat the mucus up and out of the body."

For over a decade, this type of model has been used to research lung diseases and has been shown to replicate the changes in the airway that you would see in a person who smokes at the moment," Gomperts said."

Next, along with similar cultures that had not been exposed, the group infected the cultures exposed to cigarette smoke with live SARS-CoV-2 virus and the two groups were compared. The researchers saw between two and three times as many infected cells in the models exposed to smoke.

In the absence of ABSC proliferation, they observed a rise in the number of contaminated airway cells after cigarette smoke exposure.

Digging further the researchers determined that smoking resulted, at least in part, in more serious SARS-CoV-2 infection by blocking the action of messenger proteins called interferons in the immune system. The authors wrote that the cultures' single cell profiling showed that after cigarette smoke exposure to infection, the normal interferon response was decreased.

In the early immune response of the body, interferons play a critical role by activating infected cells to produce proteins to attack the virus, calling for additional immune system help, and alerting uninfected cells to prepare to fight the virus. It is understood that cigarette smoke reduces the interferon response in the airways.

They added that treatment with Interferon β-1 for cigarette smoke-exposed ALI cultures abrogated the viral infection, "suggesting a possible mechanism for more severe viral infection."

"Smoking cigarettes is like creating holes in these walls, if you think of the airways as the high walls that protect a castle," Gomperts said. "Smoking decreases natural defences and makes it possible for the virus to set in."

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