Novel Technique Provides Detailed Map Of Lung Pathology In C
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A team has used advanced technology and analytics to map, at single-cell resolution, the cellular landscape of diseased lung tissue in severe COVID-19 and other infectious lung diseases. The researchers imaged autopsied lung tissue in a way that simultaneously highlighted dozens of molecular markers on cells. Analysing these data using novel analytical tools revealed new insights into the causes of damage in these lung illnesses.

The main technology the investigators employed in the study, called imaging mass cytometry, largely overcomes those limitations. It uses a collection of metal-tagged antibodies that can simultaneously label up to several dozen molecular markers on cells. Altogether over 650,000 cells were analysed.

The researchers applied the method to 19 lung tissue samples autopsied from patients who had died of severe COVID-19, acute bacterial pneumonia or bacterial or influenza-related acute respiratory distress syndrome, plus four lung tissue samples autopsied from people who had had no lung disease.

According to the researchers, the findings in samples from COVID-19 cases were broadly consistent with what is known about the disease, but clarified this knowledge in much finer detail. They showed that alveolar epithelial cells, which mediate the lungs’ gas-exchange function, are the main targets of infection by SARS-CoV-2.

The analysis suggested that these infected cells are not solely singled out for attack by lung-infiltrating immune cells, which may help explain why inflammation often keeps worsening in severe COVID-19 and ends up causing such extensive and relatively indiscriminate damage. One surprise for the team was that age and sex, two major factors in mortality risk for COVID-19, made no apparent difference at the histologic level, once COVID-19 had progressed to the severe stage.

The results also showed that macrophages are much more abundant in the lungs of severe COVID-19 patients compared to other lung diseases, whereas neutrophils are most prevalent in bacterial pneumonia – a distinction that may be relevant to the development of future treatments for these infectious diseases.