Nasal antivirus response could determine COVID-19 severity, says UMMC study


JACKSON, Miss. (WJTV) – According to researchers at the University of Mississippi Medical Center (UMMC) in Jackson, some people infected with SARS-CoV-2 (the virus that causes COVID-19) experience few symptoms. However, others develop the disease that leads to hospitalization, mechanical ventilation, or even death.

Researchers are working to determine which patients may be more at-risk before symptoms develop. They worked with a multi-institution team and published their findings online July 23 in the journal Cell. The paper shows how the response of different nasal cells to the early stages of infection may predict the progression of COVID-19.

Health experts said the findings could be life-changing for people who are headed toward a severe case of COVID-19.

Dr. Sarah Glover, professor of medicine and director of the Division of Digestive Diseases, led the UMMC-based portion of the work in collaboration with researchers at the Ragon Institute of Massachusetts General Hospital, the Broad Institute, the Massachusetts Institute of Technology, and Boston Children’s Hospital/Harvard University.

“The nasopharynx is an entry point for understanding immunology for COVID-19,” Glover said. The nasopharynx is the area where the nasal cavity meets the throat. This is the area health care workers target when they take a swab sample to test for COVID-19.

The abundance and availability of nasal swabs presents a “way to study the mucosal immunology in COVID-19 patients without being overly invasive,” she said.

Glover and her colleagues gathered 58 swabs from UMMC adult patients, including 35 with confirmed COVID-19 ranging from mild to severe. As controls, they also collected 17 samples from healthy volunteers and six from patients with respiratory failure not caused by COVID-19.

They used genetic sequencing technology to identify different nasopharynx cell types from the swabs. They studied the cells’ RNA, the molecules that translate DNA’s instructions into protein’s functions. They were able to see a snapshot of each single cell’s response to SARS-CoV-2 during the early stage of infection.

According to the study, people who went on to develop mild or moderate COVID-19 symptoms had cells with a stronger anti-viral immune response than people who developed severe disease. This happened even though the two groups had similar viral loads and similar health statuses prior to COVID-19.

“This virus causes significant distortion of the innate immune system,” Glover said, adding that SARS-CoV2 “changed the makeup of the cells in the nasopharynx of people with severe disease.”

Among COVID-19 patients, they found more mucus-producing secretory cells and fewer particle-filtering ciliated cells. They also found that patients with severe COVID-19 had more macrophages, the immune cells that help lead to the cytokine storm often seen in serious cases. Another part of the study showed that SARS-CoV-2 targets particular kinds of cells.

The samples in this study came from patients treated between April and September 2020, encompassing the first wave of Mississippi cases. Glover and colleagues are working on a follow-up study to compare these initial findings to patients with Delta-variant COVID-19 or breakthrough infections post-vaccination.

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