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November 16, 2020 // -- Researchers at Vanderbilt University Medical Center (VUMC) and colleagues have identified a key factor that reveals why COVID-19 appears to be a priority for adults and the elderly, and that young children are more likely to survive.
study found that children's lungs and respiratory endottor cells expressed relatively low levels of specifically recognizable sars-CoV-2.
findings, published today in journal The Journal of Clinical Investigation, support the treatment or prevention of COVID.com-19 in older adults by blocking the subject.
Jennifer Sucre, assistant professor of pediatrics who led the study, said: "Our study provides a biological basis for why babies and young children in particular seem less likely to be infected or have no serious symptoms of the disease.
Sucre and Kropski are the authors of the paper.
Bryce Schuler is the first author of the paper and a pediatric and genetic resident at VUMC.
about SARS-CoV-2, we still have a lot of unknowns.
but well-known fact is that when viral particles are inhaled into the lungs, their prickly proteins attach to the molecular surface of ACE2 (a subject on the surface of lung cells).
a cytoenzyme called TMPRSS2 shreds the hedgehog protein, allowing the virus to fuse the cell membrane and "break into" the cell.
enters the virus, the virus hijacks the genetic mechanisms of the cells to replicate their RNA.
Sucre and Kropski, who have been working together since 2016 on lung disease in premature children and adults, wanted to know whether TMPRSS2 was associated with higher levels of COVID-19 symptoms observed in older adults than in older children.
Sucre said: "Our research has been focused on understanding the development of the lungs and the differences in injuries between infant and adult lungs.
study, we actually took the opposite approach and were able to see how the developing lungs protected them from SARS-CoV-2 infection.
, a member of the International Human Cell Atlas (HCA) Lung Bios network, and their colleagues used single-cell RNA sequencing techniques to build data sets on lung development in mice.
technology can detect the expression of genes in individual cells of tissues such as the lungs.
this way, researchers were able to track the expression of genes known to be involved in the body's response to COVID-19 over time.
found that although the ACE2 gene was expressed at low levels in the lungs of mice, "the remarkable characteristic of TMPRSS2 was that it had a significant increase in expression trajectory during development".
with the help of VUMC pathologists, the researchers obtained and analyzed samples of people's lungs collected from different age-related feeders and confirmed that the trajectory of TMPRSS2 expression was similar to that of mice.
Sucre said: "We found a significant increase in (TMPRSS2) expression with age, and we have observed this at both gene and protein levels.
also used fluorescent probes to analyze autopsy specimens from three patients who died of COVID-19 and found the virus in three cells that express TMPRSS2.
TMPRSS2 is known for its role in the development of prostate cancer.
blocking enzyme has been approved for the treatment of advanced prostate cancer and is currently being clinically tested as a potential treatment for COVID-19.
Sucre said: "We believe that TMPRSS2 may be an attractive target for treatment and may be a target for preventing high-risk groups of people at high risk of COVID exposure (prevention of infection).
" () Source: Why does COVID-19 seem to spare children? New study offers an answer original source: Bryce A. Schuler et al, Age-decided expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium, Journal of Clinical Investigation (2020). DOI: 10.1172/JCI140766