Why Does COVID-19 Seem to Spare Children? Research Shows Lower Expression of Key TMPRSS2 Enzyme Used to Aid Viral Fusion to Target Cells

Researchers at Vanderbilt University Medical Center (VUMC) and their colleagues have determined a key factor as to why COVID-19 appears to infect and sicken adults and older people preferentially, while seeming to spare younger children. Children have lower levels than adults of an enzyme/co-receptor (TMPRSS2) (image) that SARS-CoV-2, the RNA virus that causes COVID-19, needs to invade airway epithelial cells in the lung. The findings, published online on November 12, 2020 in the Journal of Clinical Investigation, support efforts to block the enzyme to potentially treat or prevent COVID-19 in older people. The article is titled “Age-Determined Expression of Priming Protease TMPRSS2 and Localization of SARS-CoV-2 in Lung Epithelium.” "Our study provides a biologic rationale for why particularly infants and very young children seem to be less likely to either get infected or to have severe disease symptoms," said Jennifer Sucre, MD, Assistant Professor of Pediatrics (Neonatology), who led the research with Jonathan Kropski, MD, Assistant Professor of Medicine. Dr. Sucre and Dr. Kropski are co-corresponding authors of the JCI aticle. Bryce Schuler, MD, PhD, a resident in Pediatrics and Genetics at VUMC and postdoctoral fellow in the Vanderbilt Stimulating Access to Research in Residency program, is the paper's first author. There is still much to learn about SARS-CoV-2. But this much is known: after a viral particle is inhaled into the lungs, protein "spikes" that stick out from the virus body like nail studs in a soccer ball attach to ACE2, a receptor on the surfaces of certain lung cells.A cellular enzyme called TMPRSS2 (transmembrane protease, serine 2) (https://en.wikipedia.org/wiki/TMPRSS2) slices up the spike protein, enabling the virus to fuse into the cell membrane and "break into" the cell.
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