Same Nasal Swabs Used to Diagnose COVID-19 Could Also Identity Potentially Severe Cases

Researchers at the Ragon Institute of MGH, MIT, and Harvard (Cambridge, MA, USA), and the Broad Institute of MIT and Harvard (Cambridge, MA, USA), along with the team at Boston Children’s Hospital (BCH); MIT; and the University of Mississippi Medical Center (UMMC) studied cells taken from nasal swabs of patients at the time of their initial COVID-19 diagnosis, comparing patients who went on to develop mild COVID-19 to those who progressed into more severe disease and eventually required respiratory support. Their results showed that patients who went on to develop severe COVID-19 exhibited a much more muted antiviral response in the cells collected from those early swabs, compared to patients who had a mild course of disease.

First, the team found that the antiviral response, driven by a family of proteins called interferons, was much more muted in patients who went on to develop severe COVID-19. Second, patients with severe COVID-19 had higher amounts of highly inflammatory macrophages, immune cells that contribute to high amounts of inflammation, often found in severe or fatal COVID-19. Since these samples were taken well before COVID-19 had reached its peak state of disease in the patients, both these findings indicate that the course of COVID-19 may be determined by the initial or very early response of the nasal epithelial and immune cells to the virus. The lack of strong initial antiviral response may allow the virus to spread more rapidly, increasing the chances that it can move from the upper to lower airways, while the recruitment of inflammatory immune cells could help drive the dangerous inflammation in severe disease.

Finally, the team also identified infected host cells and pathways associated with protection against infection — cells and responses unique to patients that went on to develop a mild disease. These findings may allow researchers to discover new therapeutic strategies for COVID-19 and other respiratory viral infections. If, as the team’s evidence suggests, the early stages of infection can determine disease, it opens a path for scientists to develop early interventions that can help prevent severe COVID-19 from developing. The team’s work even identified potential markers of severe disease, genes that were expressed in mild COVID-19 but not in severe COVID-19.

"Nearly all our severe COVID-19 samples lacked expression of several genes we would typically expect to see in an antiviral response," said Carly Ziegler, a graduate student in the Health Science and Technology program at MIT and Harvard and one of the study’s co-first authors. "If further studies support our findings, we could use the same nasal swabs we use to diagnose COVID-19 to identity potentially severe cases before severe disease develops, creating an opportunity for effective early intervention."

Related Links:
Ragon Institute of MGH, MIT, and Harvard
Broad Institute of MIT and Harvard