Early COVID-19 reactions in the nose and throat predict the severity of the disease

The body’s first encounter with SARS-CoV-2, the virus behind COVID-19, occurs in the nose and throat, or in the nasopharynx. Journal new research cell The first reaction on the battlefield suggests that it helps determine who develops a severe illness and who treats it mildly or disease-free.

Build on Works released last year Identifying virus-susceptible cells and a team of collaborators at the Boston Children’s Hospital, MIT, and the University of Mississippi Medical Center comprehensively mapped SARS-CoV-2 infections in the nasopharynx. From April to September 2020, they obtained samples from the nasal swabs of 35 adults with COVID-19, ranging from mild to severe illness. They also obtained cotton swabs from 17 control subjects and 6 patients who were intubated but did not have COVID-19.

“Why some people get sick more than others was one of the most mysterious aspects of the virus from the beginning,” he says. José Ordovás-Montañés, PhD, Boston Children’s Co-Principal Investigator Bruce Howitz, MD, PhD Boston Children, Dr. Alex Sharek of MIT, Dr. Sarah Glover of the University of Mississippi. “Many studies looking for risk predictors are looking for signs in the blood, but the blood may not be the right place to actually see it.”

COVID-19’s First Battlefield: Nasopharynx

To get a better idea of ​​what’s happening in the nasopharynx, researchers sequenced the RNA of each cell one cell at a time. (In the sense of all the work involved, each patient’s swab produced an average of 562 cells.) RNA data showed that the team had cells containing virus-derived RNA (signs of infection). , I was able to identify which cells are present. A gene that the cell switched on and off accordingly.

It was quickly revealed that the epithelial cells that line the nose and throat undergo major changes in the presence of SARS-CoV-2. The cells were generally diversified in type. Increased mucus-producing secretory cells and goblet cells. At the same time, there was a significant loss of mature ciliated cells that cleared the airways, and an increase in immature ciliated cells (probably trying to compensate).

The team discovered SARS-CoV-2 RNA in a variety of cell types, including immature ciliated cells and specific subtypes of secretory cells, goblet cells, and squamous epithelial cells. Infected cells have more genes turned on that are involved in a productive response to infection compared to uninfected “bystander” cells.

Failed initial immune response

An important finding was made when the team compared nasopharyngeal swabs from people of different severity of COVID-19 disease.

• With people Mild or moderate COVID-19Epithelial cells showed increased activation of genes involved in antiviral reactions, especially those stimulated by type I interferon. This is a very early warning to restore the broader immune system.
• For developed people Severe COVID-19, Requires ventilator, antiviral response is significant Slow down.. Most notably, those epithelial cells showed a muted response to interferon, despite carrying large amounts of the virus. At the same time, their swabs increased the number of macrophages and other immune cells that promoted the inflammatory response.

“Anyone infected with severe COVID-19 could not increase their defenses due to the early slowing of interferon response in epithelial cells,” says Ordovás-Montañés. “Getting the right amount of interferon at the right time can be important in combating SARS-CoV-2 and other viruses.”

Do you boost the interferon response in the nose?

As a next step, researchers plan to investigate what is causing the muted interferon response in the nasopharynx. Evidence suggests that this can also occur with the new SARS-CoV-2 mutant. They also explore the potential of nasal drops and nasal drops to enhance the interferon response in people with early COVID-19 infections.

Using the right amount of interferon at the right time can be important in combating SARS-CoV-2 and other viruses. “

“For whatever reason, people with suppressed interferon responses may be more susceptible to future infections beyond COVID-19,” says Ordovás-Montañés. “The question is how to make these cells more responsive.”

Carly Ziegler, Vincent Miao, Andrew Navia, Joshua Bromley of MIT and Harvard. Anna Owings of the University of Mississippi; Ying Tang of Boston Children’s Hospital was the co-lead author of this treatise. Funders include the Chanzuckerberg Initiative DAF, National Institutes of Health, New York Stemcell Foundation, Richard and Susan Smith Family Foundation, AGA Research Foundation, Food Allergology Initiative, Leona M. and Harry B. Helmsley Charitable Organizations. increase. Trust, Crohn’s and Colitis Foundation, Bill and Melinda Gates Foundation, and Ragon Institute at MGH, MIT, and Harvard.

Explore COVID-19 studies at Boston Children’s Hospital