Response to COVID-19 in Nasopharynx May Determine Disease Severity

The nasal mucosa was seen to be an essential determinant of overall disease trajectory.

A recent study conducted by investigators from the Boston Children’s Hospital, in collaboration with the Massachusetts Institute of Technology and the University of Mississippi Medical Center, has found that the first responses to COVID-19 in the nasopharynx may determine an individual’s future disease severity.

Results from the study were published in the journal Cell.

"Why some people get more sick than others has been one of the most puzzling aspects of this virus from the beginning," José Ordovás-Montañés, co-senior author on the study said. "Many studies looking for risk predictors have looked for signatures in the blood, but blood may not really be the right place to look."

For the study, the team of investigators collected nasal swabs from 35 adults with COVID-19, 17 control subjects and 6 intubated patients who did not have COVID-19, between April and September of 2020.

They then sequenced the RNA in each cell, which enabled them to pinpoint which cells were present, which ones contained RNA from the virus and which genes the cells were turning on and off in response to the infection.

Finds from the study showed that in those with mild or moderate COVID-19, the epithelial cells showed an increased activation of genes that involve antiviral responses, including genes that stimulate type 1 interferon which is an early alarm for the immune system.

Additionally, in people who developed severe disease, antiviral responses were seen to be blunted and that their epithelial cells had a muted response to interferon. Their swabs also had increased levels of macrophages and other immune cells which boost the inflammatory response.

“Together, our work and that of our colleagues suggest that several mechanisms that restrict interferon-mediated viral control in the upper respiratory epithelium can enable progression to severe COVID-19, that these causes may be multifactorial and rooted in human diversity, and yet they converge on impaired intrinsic immunity to SARS-CoV-2 in nasal epithelial cells,” the authors wrote. “Further, it suggests that there may be a clinical window in which severe disease can be subverted by focusing preventative or therapeutic interventions early within the nasopharynx bolstering anti-viral responses and curbing pathological inflammatory signaling prior to development of severe respiratory dysfunction or systemic disease.”