Overexpression of Neutrophils Causes 'Severe COVID-19'

Korea Advanced Institute of Science and Technology Discovers Biomarker Distinguishing Critically Ill Patients
Neutrophil Overexpression Identified as New Cause of Severe COVID-19
Severity Improved Using Glucocorticoid Inhibitors

[Asia Economy Reporter Junho Hwang] A biomarker that can easily distinguish between severe and mild cases of COVID-19 has been discovered by domestic researchers. This finding raises expectations not only for rapid response to severe patients but also for the development of treatments.

The research team led by Professor Heungkyu Lee of the Graduate School of Medical Science and Engineering at the Korea Advanced Institute of Science and Technology (KAIST) announced on the 7th that they identified factors determining the severity of COVID-19, and their related research paper was published in the international immunology journal 'Frontiers in Immunology.'

'Overexpression of Neutrophils' in Severe COVID-19

Mild patients exhibit a normal T cell-mediated immune response upon COVID-19 infection. The high expression of glucocorticoid receptors suppresses the expression of CXCL8, thereby regulating neutrophil infiltration. In contrast, severe patients with low glucocorticoid receptor expression show increased CXCL8 expression, leading to enhanced neutrophil infiltration. Excessive inflammatory responses by neutrophils cause damage to lung tissue epithelial cells, resulting in severe respiratory symptoms.

The research team revealed that severe COVID-19 occurs due to the overactivation of neutrophils. Neutrophils are innate immune cells that make up 50-70% of the total white blood cells in the blood. They are known to respond to bacterial or fungal infections. The team obtained these results while investigating the role of neutrophils in COVID-19.

The team analyzed single-cell genetic information from bronchoalveolar lavage fluid of mild and severe COVID-19 patients, which was publicly available in the Gene Expression Omnibus (GEO). They discovered significant damage to the lung epithelial cells of severe patients. Furthermore, they found that this damage was associated with the infiltration of neutrophils. It was confirmed that excessive expression of genes inducing inflammation from neutrophils infiltrating lung tissue causes lung tissue damage. On the other hand, gene expression related to the antiviral immunity of neutrophils was low.

Professor Heungkyu Lee stated, "This research revealed the mechanism by which severe COVID-19 occurs," adding, "It confirmed that neutrophils rushing to the lungs to kill the virus actually damage lung tissue."

Increased Neutrophil Infiltration into Lung Tissue by Chemokines such as CXCL8

Higher CXCL8 chemokine expression and neutrophil infiltration were observed in the lung lavage fluid of critically ill patients.

In particular, the research team also clarified the reason for the increased neutrophils in lung tissue. Bone marrow-derived immune cells present in the lung tissue of severe patients showed lower expression of glucocorticoid receptor (NR3C1) compared to mild patients. The team explained that this leads to the expression of chemokines such as CXCL8 within bone marrow-derived immune cells like macrophages, which in turn increases neutrophil infiltration.

NR3C1 is a hormone produced in the adrenal cortex near the kidney and is involved in regulating various bodily functions. It is also known as a hormone that suppresses immune responses.

Professor Heungkyu Lee expressed, "With these research results, we expect to provide a starting point for developing treatments that improve the severity of COVID-19 by utilizing glucocorticoid inhibitors such as dexamethasone."

This content was produced with the assistance of AI translation services.