Filenews 29 July 2021
The body's first exposure to SARS-CoV-2, the virus that causes COVID-19, occurs through the nasopharyngeal cavity. A new study published in Cell, therefore, suggests that the first response to this "invasion" determines who will develop a serious disease and who will pass the infection gently or without any symptoms at all.
Based on work published last year in which vulnerable coronavirus cells were identified, a team of scientists from Boston Children's Hospital, MIT and the University of Mississippi Medical Center detailed sars-coV-2 infection in the nasopharyngeal cavity. Specifically, they collected smears from the nasal cavity of 35 adults with COVID-19, some of whom had mild symptoms while others were seriously ill. They also took samples from 17 control individuals and six patients who had been intubated but did not suffer from COVID-19.
"Why some people get worse than others is one of the most intractable aspects of this virus. Many studies looking at risk factors have looked for signs in the blood, but perhaps ultimately blood is not the right place to look," says José Ordovás-Montañés, from Children's Hospital and one of the study's lead researchers.
The first "battle" with COVID-19: the nasopharyngeal cavity
To get a detailed picture of what is happening in the nasopharyngeal cavity, the researchers sequenced the RNA in each cell so that they could identify which cells were there, which contained virus RNA - an indication of infection - and which genes activated or deactivated the cells in response.
It soon became clear that the epithelial cells in the nose and pharynx undergo significant changes due to the coronavirus, as they all differed in their type. The team also found SARS-CoV-2 RNA in a huge variety of cell types, with infected cells having more activated genes involved in the productive response to infection.
Failed early immune response
The most important finding came when the team compared nasopharyngeal samples from people with different severity of COVID-19 disease:
- In sufferers of mild to moderate COVID-19, epithelial cells showed increased activation of genes with anti-responses - and especially in genes activated by type I interferon, a very early alarm that alertes the wider immune system.
- In people who developed severe COVID-19 and needed mechanical breathing support, the anti-anxiety responses were almost undetectable. Specifically, their epithelial cells had a "silent" response to interferon, despite the high blood load. At the same time, the samples had an increased number of macrophages and other immune cells that enhance inflammatory responses.
"Anyone with severe COVID-19 had a sharp interferon response very early in epithelial cells and was never able to strengthen their defenses. The right amount of interferon at the right time could be the focus of treating SARS-CoV-2 and other viruses," says Dr. Ordovás-Montañés.
Enhancing the response of interferon to the nose
In their next step, the researchers plan to investigate what causes the "silent" response of interferon to the nasopharyngeal cavity, which data suggest may also be the case with new mutations of SARS-CoV-2. They also want to explore the possibility of increasing the interferon response in people with early COVID-19 infection, perhaps through nasal sprays or droplets.
"It is possible that, regardless of the reasons, people with a 'silent' interferon response will be vulnerable to future infections beyond COVID-19. The question is how can we make these cells respond more," the scientists conclude.
