Chronic Lung Disease Causes Severe COVID-19 Infections

A new study from the Translational Genomics Research Institute suggests that the airway cells of those with chronic lung disease are primed for COVID-19 infection, meaning that COVID-19 infection in those patients could result in more severe symptoms, poor outcomes, and even death.

The study outlines the genetic changes caused by chronic lung disease in the molecular makeup of a variety of cells, including the epithelial cells that line the lungs and airways.

According to the study, changes to the cells can enable the COVID-19 virus to enter the body, replicate, and cause a drastic immune response that fills the lungs with fluid. Severe reactions can result in patients requiring respirators and lengthy hospitalizations.

The team of scientists spelled out the genetic code of 611,398 cells from several databases using single-cell RNA sequencing technology. The data represented both individuals with healthy lungs and those with chronic lung disease. The sequencing and analysis allowed researchers to discover molecular characteristics that make for worse COVID-19 outcomes.

“Our results suggest that patients with chronic lung disease are molecularly primed to be more susceptible to infection by SARS-CoV-2,” Nicholas Banovich, PhD, an Associate Professor in TGen’s Integrated Cancer Genomics Division, and one of the study’s senior authors said in a press release.

Additionally, researchers identified older-age, male-gender, smoking, and other comorbidities as COVID-19 risk factors worsened by chronic lung disease.

“It was recognized early in the pandemic that patients with chronic lung diseases were at particularly high risk for severe COVID-19, and our goal was to gain insight into the cellular and molecular changes responsible for this,” said Jonathan Kropski, MD, Associate Professor of Medicine and Cell and Developmental Biology at Vanderbilt University Medical Center, and a co-senior author of the study.

Researchers focused their study on changes in AT2 cells, looking specifically at cellular pathways and expression levels of genes tied to COVID-19. The team established a “viral entry score” and discovered a higher score among cells from individuals with chronic lung disease.

They also looked at changes in immune cells and found dysregulated gene expression associated with hyper-inflammation and sustained cytokine production, two symptoms of severe COVID-19 infections.

“The genetic changes in immune cells, especially in specialized white blood cells known as T cells, may diminish the patient’s immune response to viral infection and lead to a higher risk of severe disease and poor outcomes in patients with chronic lung disease,” said Linh Bui, PhD, a post-doctoral fellow in Banovich’s lab, and one of the study’s lead authors.

“Our data suggest that the immune microenvironment at both the molecular and cellular levels in lungs damaged by chronic diseases may promote severe COVID-19,” Bui said.