In a new study, researchers found a key factor as to why COVID-19 appears to infect and sicken adults and older people preferentially while seeming to spare younger children.
They found children have lower levels of an enzyme/co-receptor that SARS-CoV-2, the RNA virus that causes COVID-19, needs to invade airway epithelial cells in the lung.
The findings support efforts to block the enzyme to potentially treat or prevent COVID-19 in older people.
The research was conducted by a team at Vanderbilt University.
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 like nail studs in a soccer ball attached to ACE2, a receptor on the surfaces of certain lung cells.
A cellular enzyme called TMPRSS2 chops up the spike protein, enabling the virus to fuse into the cell membrane and “break into” the cell.
Once inside, the virus hijacks the cell’s genetic machinery to make copies of its RNA.
The researchers wondered if TMPRSS2 had something to do with the greater severity of COVID-19 symptoms observed in older people compared to children.
They had built a dataset on lung development in the mouse using a technique called single-cell RNA-sequencing.
The technique can detect the expression of genes in individual cells of tissues such as the lung. In this way, the researchers were able to track the expression of genes known to be involved in the body’s response to COVID-19 over time.
They found that while the gene for ACE2 was expressed at low levels in the mouse lung, TMPRSS2 stood out as having a really striking trajectory of increased expression during development.
The researchers obtained and analyzed human lung specimens collected from donors of different ages, and confirmed a similar trajectory in TMPRSS2 expression to what they’d found in mice.
They found that the expression of (TMPRSS2) goes up significantly with aging.
The researchers also used fluorescent probes to analyze autopsy specimens from three patients who died of COVID-19 and found the virus in three types of cells that express TMPRSS2.
TMPRSS2 is well known for its role in the development of prostate cancer.
Drugs that block the enzyme and which have been approved for the treatment of advanced prostate cancer currently are being tested clinically as potential treatments for COVID-19.
The researchers think TMPRSS2 could be an attractive target both in treatment and potentially as prophylaxis for (preventing infection in) people at high risk of COVID exposure.
One author of the study is Jennifer Sucre, MD, assistant professor of Pediatrics (Neonatology).
The study is published in the Journal of Clinical Investigation.
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