Like preparing a bomb, cells damaged by chronic lung disease can cause severe COVID

The results of a study by an international scientific team co-led by the Translational Genomics Research Institute (TGen), a subsidiary of City of Hope, suggest that, like pouring water on a wellhead before pumping, cells Respiratory tract cells of patients with chronic lung disease are “prepared” for COVID-19 virus infection, resulting in more severe symptoms, worse outcomes, and a higher likelihood of death.

The study, published today in Communications on Nature—Details the file genetic changes caused by chronic lung disease in the molecular composition of several cells, including epithelial cells which run through the lungs and airways. The study details how these changes may help SARS-CoV-2, the virus that causes COVID-19, enter the body, reproduce, and trigger out-of-control control. immune response which fills the lungs with fluids and often results in patients needing respirators and prolonged hospitalizations.

The team used monocellular RNA sequencing technology to explain the genetic code of 611,398 cells from various databases, representing both those with healthy (control) lungs and those with chronic lung disease. Sequencing and analysis allowed the researchers to identify molecular features that may explain worse COVID-19 outcomes.

“Our results suggest that patients with chronic lung disease are molecularly prepared to be more susceptible to SARS-CoV-2 infection,” said Nicholas Banovich, Ph.D., associate professor in the Integrated Division of Cancer Genomics. of TGen and one of the senior authors of the study. Dr. Banovich is one of the main participants in the Lung Biological Network of the Atlas of Human Cells, dozens of members, representing more than 80 institutions around the world, also contributed to this study.

In addition, old age, male sex, smoking and comorbidities such as high blood pressure, obesity, and diabetes are COVID-19 risk factors that are exacerbated by chronic lung disease, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and especially idiopathic pulmonary fibrosis. FPI), a progressive frightening and hardening of the lung tissue.

“Early in the pandemic, it was recognized that patients with chronic lung disease had a particularly high risk of severe COVID-19, and our goal was to know the cellular and molecular changes responsible for this fact,” Jonathan said. Kropski, MD, Associate Professor of Cellular and Developmental Medicine and Biology at Vanderbilt University Medical Center and co-senior author of the study.

Changes in lung cells and immune cells

The researchers specifically looked for changes in AT2 cells, a major type of lung epithelial cell, focusing on cellular pathways and expression levels of COVID-19-associated genes. They established a “viral entry score,” a compound of all genes associated with SARS-CoV-2, and found higher scores among the cells of patients with chronic lung disease.

They also explored changes in immune cells and discovered deregulated gene expression associated with hyperinflammation and sustained cytokine production, two signature symptoms of severe SARS-CoV-2 infection. So-called cytokine storms in COVID-19 patients trigger a cascade of immune cells that flood the lungs, causing severe organ damage.

“Genetic changes in immune cells, especially in specialized white blood cells known as T cells, can decrease the patient’s immune response to viral infection and lead to an increased risk of serious illness and poor outcomes in patients with chronic lung disease”Said Linh Bui, Ph.D., postdoctoral fellow in Dr. 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 the lungs damaged by chronic disease may favor severe COVID-19,” said Drs. Bui.

Vanderbilt University Medical Center, Yale School of Medicine, Harvard Medical School, Baylor College of Medicine, and the Department of Veterans Affairs Medical Center made significant contributions to this study. In addition, there are several institutes in the UK, including: Imperial College London, the Royal Brompton and Harefield National Health System Foundation Trust, Edinburgh University Medical School and the Royal Infirmary in Edinburgh.