The results of a large international study showed that patients with pre-existing lung diseases are most susceptible to severe complications in COVID-19. The article is published in the journal Nature Communications.

Researchers from ten countries, using single-cell RNA sequencing technology, analyzed the genetic code of 611,398 cells from various databases representing lung cells, both healthy people and those suffering from chronic diseases. It turned out that the respiratory tract cells of patients with chronic lung diseases are better “prepared” for infection with coronavirus, which leads to more severe symptoms of COVID-19 and a greater probability of death.

The study describes in detail the genetic changes in the molecular composition of various cells, including epithelial cells lining the lungs and respiratory tract, caused by chronic lung diseases. According to the authors, these changes help the SARS-CoV-2 virus to enter cells more easily, multiply and cause an uncontrolled immune response, as a result of which the lungs are filled with fluid, and patients need to be connected to ventilators and long-term hospitalization.

“Our results show that patients with chronic lung diseases are molecularly predisposed to greater susceptibility to SARS-CoV-2 infection,” the head of the study, Dr. Nicholas Banovich, associate professor of the Department of Complex Cancer genomics from the American Research Institute for Translational Genomics (TGen), is quoted in a press release.

These diseases include: chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ISL), idiopathic pulmonary fibrosis (ILF), progressive scarring and compaction of lung tissue, and additional risk factors include old age, male sex, smoking, high blood pressure, obesity and diabetes.

“At an early stage of the pandemic, it was recognized that patients with chronic lung diseases are at particularly high risk of severe COVID-19,” says another study participant, Dr. Jonathan Kropski, professor of medicine, cell biology and developmental biology at Vanderbilt University Medical Center in the United States. — Our goal was to get an idea of the cellular and molecular changes responsible for this.”

First of all, the scientists looked for changes in AT2 cells, the main type of lung epithelial cells, paying special attention to the cellular pathways and expression levels of genes associated with COVID — 19. They also evaluated changes in immune cells and found unregulated gene expression in patients with chronic lung diseases associated with hyperinflammation and sustained cytokine production — two characteristic symptoms of severe coronavirus infection. The so-called cytokine storm triggers cascading reactions of cell formation in patients with COVID-19, which flood the lungs, causing serious organ damage.

“Genetic changes in immune cells, especially in specialized white blood cells such as T cells, can reduce the patient’s immune response to a viral infection and lead to a higher risk of severe disease and poor outcomes in patients with chronic lung disease,” explains the first author of the article, Dr. Linh T. Bui, a researcher in Dr. Banovich’s laboratory.

The authors found that the immune environment in the lungs damaged by chronic diseases contributes to the severe form of COVID-19.