Are NETS the link between COVID-19 and ILD?
In response to the COVID-19 pandemic, researchers are investigating how the virus causes lung damage, in order to help identify treatment strategies. There is some overlap between the mechanisms being studied in COVID-19 and Interstitial Lung Disease (ILD). One of these is the production of structures known as ‘NETs’ in the lungs. A clinical trial currently led by Professor Porter at UCL aims to understand whether targeting these NETs improves outcomes for COVID-19 patients. This continues a line of work investigating the role of NETs in ILD.
NETs is short for Neutrophil Extracellular Traps. They contain DNA, enzymes, and proteins, and are produced by the neutrophil (a white blood cell) to fight infection. The role of NETs in COVID-19 pneumonia is also under investigation. A study published last year showed that some of the markers of NETs used in Professor Porter’s ILD study were found in blood samples from COVID-19 patients (2). The levels of these markers correlated with other blood tests known to signify inflammation. Furthermore, adding blood samples from patients with COVID-19 to healthy neutrophils in the lab caused them to produce NETs. This could mean that NET production is related to lung damage in patients with COVID-19 pneumonia.
Further research is needed to determine whether NETs are a cause or by-product of lung damage in these diseases. However, knowing that NETs are associated with severe COVID-19, and that they are present in the lungs of patients with ILD, means that they could be used as a ‘biomarker’ – a molecular signal of lung damage. Promisingly, it could mean that reducing the activity of NETs in the lungs is a potential treatment strategy in the future.
The crossover between NETs in COVID-19 and ILD demonstrates the importance of ongoing research in this field. The team at UCL Respiratory are incredibly grateful for the support of Breathing Matters in helping to facilitate this research.
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- Khawaja AA, Chong DLW, Sahota J, Mikolasch TA, Pericleous C, Ripoll VM, Booth HL, Khan S, Rodriguez-Justo M, Giles IP, Porter JC. Identification of a Novel HIF-1α-αMβ2 Integrin-NET Axis in Fibrotic Interstitial Lung Disease. Front Immunol. 2020 Oct 15;11:2190. doi: 10.3389/fimmu.2020.02190. PMID: 33178179; PMCID: PMC7594517.
- Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020 Jun 4;5(11):e138999. doi: 10.1172/jci.insight.138999. PMID: 32329756; PMCID: PMC7308057.