Multiple studies, including this Johns Hopkins Medicine one published in August 2021, have demonstrated evidence that olfactory-supporting cells are the entry point for SARS-CoV-2. These studies are further boosted by and add clues as to why loss of smell (and taste) is a common symptom of COVID-19.
Researchers at Baylor College of Medicine have now exploited this fact to develop a human nose organoid that can provide a much a better understanding of the first steps toward disease and even shed light on potential new therapies.
“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,” said Pedro Piedra, professor of molecular virology and microbiology at Baylor College of Medicine. “We have successfully developed human nose organoids from both adults and infants.”
The model was more complex than others since the lining the inside of the nose, the epithelium, are exposed to air on one side but the blood circulatory system on the other. According to the researchers, they replicated this in the lab using nose epithelium harvested with a nasal swab.
“We grow the harvested epithelium in tissue culture plates that provide an air-liquid interphase, where the top side of the epithelium is exposed to air and the bottom side is bathed in liquid with nutrients and other factors,” explained first author Anubama Rajan, postdoctoral associate in the Piedra lab.
The model Rajan and team created proved to be compatible with not only SARS-CoV-2 but pediatric RSV (respiratory syncytial virus), as well.
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 air side of the culture plates, observing the changes that occurred on the nose organoid. The responses were different for each virus.
According to the results, published in mBio, SARS-CoV-2 induced severe damage to the epithelium, no interferon response and minimal mucus secretion. Meanwhile, RSV induced abundant mucus secretion and a profound interferon response.
The scientists also used the human nose organoid to test the efficacy of palivizumab, an FDA-approved monoclonal antibody to prevent severe RSV disease in high-risk infants. In this case, they placed the antibody in the liquid-filled chamber to more closely resemble the human experience—where therapeutic antibodies enter via blood circulation. According to the researchers, palivizumab effectively prevented RSV infection in the model.
The study marks the first time scientists have described a non-invasive, reproducible and reliable approach to establishing human nose organoids that enable long-term studies. An advantage to using the novel human nose organoid system is that it can reveal how a person’s initial control of infection occurs and provide insights into what would make a person more susceptible to a virus—whether that is SARS-CoV-2, RSV, other respiratory viruses or even disease-causing microbes.