WASHINGTON: Scientists have found a key factor that may explain why the new coronavirus predominantly affects adults and older people while it appears to save younger children, a breakthrough that may lead to the development of new treatment strategies for Covid-19.
According to researchers, including those at Vanderbilt University Medical Center (VUMC) in the US, children have lower levels of a receptor protein that the SARS-CoV-2 coronavirus needs to invade the epithelial cells of the airways in the lung.
The findings, published in the Journal of Clinical Investigation, support efforts to block this protein to potentially treat or prevent Covid-19 in older people, the scientists said.
“Our study provides a biological rationale for why, in particular, very young infants and children appear to be less likely to become infected or have severe symptoms of the disease,” said Jennifer Sucre, a co-author of the VUMC study.
After a viral particle is inhaled into the lungs, the protein “spikes” bind to ACE2, a receptor on the surface of certain lung cells, the researchers explained.
They said that another cellular protein called TMPRSS2 cuts the spike, allowing the virus to fuse at the cell membrane and “break into” the cell.
“Our research has always focused on understanding lung development and how infant lungs differ from adult lungs in their vulnerability to injury,” Sucre said.
“In this study, in fact, we took the opposite approach and were able to see how the developing lung by its differences is protected from SARS-CoV-2 infection,” he added.
In the study, using a technique called single-cell RNA sequencing, the researchers detected gene expression in individual mouse cells from tissues such as the lung.
They tracked the expression of genes known to be involved in the body’s response to Covid-19 over time.
While the ACE2 gene was expressed at low levels in the mouse lung, “TMPRSS2 stood out as having a really surprising trajectory of increased expression during development,” said Bryce Schuler, another study co-author.
The scientists obtained and analyzed human lung samples collected from donors of different ages and confirmed a similar trajectory in TMPRSS2 expression as they had found in mice.
“What we found is that the expression of (TMPRSS2) increases significantly with aging, and we see it at the gene level and at the protein level. We see much more TMPRSS2 in older people, both in humans and in mice.” Sucre said .
Then, using fluorescent molecules to analyze autopsy samples from three patients who died of Covid-19, the researchers found the virus in three types of cells that express TMPRSS2.
They said that this receptor protein is well known for its role in the development of prostate cancer.
According to scientists, drugs that block TMPRSS2 and that have been approved for the treatment of advanced prostate cancer are currently being clinically tested as possible treatments for Covid-19.
“We believe that TMPRSS2 could be an attractive target both in treatment and potentially as prophylaxis for people at high risk of exposure to Covid,” Sucre added.
According to researchers, including those at Vanderbilt University Medical Center (VUMC) in the US, children have lower levels of a receptor protein that the SARS-CoV-2 coronavirus needs to invade the epithelial cells of the airways in the lung.
The findings, published in the Journal of Clinical Investigation, support efforts to block this protein to potentially treat or prevent Covid-19 in older people, the scientists said.
“Our study provides a biological rationale for why, in particular, very young infants and children appear to be less likely to become infected or have severe symptoms of the disease,” said Jennifer Sucre, a co-author of the VUMC study.
After a viral particle is inhaled into the lungs, the protein “spikes” bind to ACE2, a receptor on the surface of certain lung cells, the researchers explained.
They said that another cellular protein called TMPRSS2 cuts the spike, allowing the virus to fuse at the cell membrane and “break into” the cell.
“Our research has always focused on understanding lung development and how infant lungs differ from adult lungs in their vulnerability to injury,” Sucre said.
“In this study, in fact, we took the opposite approach and were able to see how the developing lung by its differences is protected from SARS-CoV-2 infection,” he added.
In the study, using a technique called single-cell RNA sequencing, the researchers detected gene expression in individual mouse cells from tissues such as the lung.
They tracked the expression of genes known to be involved in the body’s response to Covid-19 over time.
While the ACE2 gene was expressed at low levels in the mouse lung, “TMPRSS2 stood out as having a really surprising trajectory of increased expression during development,” said Bryce Schuler, another study co-author.
The scientists obtained and analyzed human lung samples collected from donors of different ages and confirmed a similar trajectory in TMPRSS2 expression as they had found in mice.
“What we found is that the expression of (TMPRSS2) increases significantly with aging, and we see it at the gene level and at the protein level. We see much more TMPRSS2 in older people, both in humans and in mice.” Sucre said .
Then, using fluorescent molecules to analyze autopsy samples from three patients who died of Covid-19, the researchers found the virus in three types of cells that express TMPRSS2.
They said that this receptor protein is well known for its role in the development of prostate cancer.
According to scientists, drugs that block TMPRSS2 and that have been approved for the treatment of advanced prostate cancer are currently being clinically tested as possible treatments for Covid-19.
“We believe that TMPRSS2 could be an attractive target both in treatment and potentially as prophylaxis for people at high risk of exposure to Covid,” Sucre added.
.
