As the world continues to adapt in the wake of the COVID-19 pandemic, scientists are zooming in on a small, often overlooked region with outsized importance: the nasal cavity. A groundbreaking study published in Nature Medicine (May 2020) by Sungnak et al. uncovers how the nose may be the primary portal through which SARS-CoV-2 enters and initiates infection—thanks to the cellular expression of key viral entry factors.
Your nose might be the virus's favorite hangout. This study shows that SARS-CoV-2’s entry proteins (ACE2 + TMPRSS2) are highly expressed in nasal goblet and ciliated cells, making them prime real estate for early infection. Next-gen nasal sprays and vaccines? Yeah, those just might be the next big thing.
The Nasal Epithelium: A Viral Welcome Mat?
Researchers utilized single-cell RNA sequencing (scRNA-seq) datasets from the Human Cell Atlas and other global repositories to map out where SARS-CoV-2 gains entry. They focused on two key molecules:
ACE2: the receptor that SARS-CoV-2 uses to enter human cells
TMPRSS2: a protease that activates the virus's spike protein, allowing fusion with the host membrane
Their investigation revealed that nasal goblet and ciliated epithelial cells—those responsible for mucus production and airway cleaning—express both ACE2 and TMPRSS2 at higher levels than any other cells in the respiratory tract.
In simpler terms: the virus finds an easy entrance right at the front door.
A Map of Vulnerability Across Human Tissues
The team compared expression of these receptors across a wide variety of human tissues—from the lungs and gut to the eye and even fetal organs. They found that:
ACE2 expression is generally low, but significantly elevated in nasal epithelial cells.
TMPRSS2 is more broadly expressed, but its co-expression with ACE2 is rare, making the nose a unique high-risk zone.
Co-expression was also observed in the cornea, esophagus, ileum, and colon, offering clues to potential transmission routes beyond respiratory droplets, including ocular or fecal-oral pathways.
Implications for Transmission and Immune Response
Interestingly, the nasal epithelial cells not only express viral entry factors—they also co-express genes linked to innate immunity, such as OAS1, MX1, and IDO1. This suggests these cells aren’t just viral entry points; they’re also first responders, possibly mounting defense responses early in infection.
The findings also align with clinical observations:
Higher viral loads in nasal swabs compared to throat swabs, even in asymptomatic individuals
The greater transmissibility (R₀) of SARS-CoV-2 compared to MERS, potentially due to its preference for the upper airway, where it can shed and spread easily
A Call for Intranasal Strategies
Given the clear role of nasal cells in early infection, this study supports the idea of intranasal delivery of vaccines or antivirals as a proactive defense strategy. If the virus enters through the nose, perhaps that’s where our medical countermeasures should begin too.
Conclusion: The Nose Knows
This study provides a cellular atlas of SARS-CoV-2’s entry routes and emphasizes the nasal epithelium as a critical front line in the fight against COVID-19. By spotlighting the molecular machinery at play in the nose, it invites researchers and public health experts to consider nasal-targeted therapies and diagnostics as essential tools in pandemic preparedness and response.
.png){kind=logo}