A team of US researchers have developed a versatile human nose organoid to understand how COVID causing virus and respiratory viruses take their first steps.

The organoid is a laboratory representation of the cells layering the inside of the nose where the first events of a natural viral infection take place. Using the organoid, researchers at Baylor College of Medicine showed key differences between the infection by SARS-CoV-2, the virus that causes COVID-19, and that of respiratory syncytial virus (RSV), a major paediatric respiratory virus.

The findings showed that SARS-CoV-2 induces severe damage to the epithelium, no interferon response (an antiviral first defence response), and minimal mucus secretion. In striking contrast, RSV induces abundant mucus secretion and profound interferon response. Preclinical models that recapitulate aspects of human airway disease are essential for the advancement of novel therapeutics and vaccines, the team wrote in the study published in the journal mBIO.

"In the case of respiratory viruses, such as SARS-CoV-2 and RSV, the infection begins in the nose when one breathes in the virus," said Dr Pedro Piedra, Professor at Baylor. "The human nose organoids we have developed provide access to the inside of the human nose, enabling us to study the early events of the infection in the lab, something we had not had before. We have successfully developed human nose organoids from both adults and infants," Piedra said.

The cells lining the inside of the nose, the epithelium, are exposed to air on one side and to the blood circulatory system on its opposite side. To study the interaction between SARS-CoV-2 or RSV and the nose epithelium, the researchers simulated a natural infection by placing each virus separately on the airside of the culture plates and studying the changes that occurred on the nose organoid.

The team observed divergent responses to SARS-CoV-2 and RSV infection. The team also used their human nose organoid model of RSV infection to test the efficacy of palivizumab, an FDA-approved monoclonal antibody to prevent severe RSV disease in high-risk infants. They found that palivizumab effectively prevented RSV infection in a concentration-dependent manner.