A new study from researchers at the George Washington University has found that certain bacteria living in the nose may influence how likely someone is to get a COVID-19 infection. Published in EBioMedicine, the research reveals that certain types of nasal bacteria can affect the levels of key proteins the virus needs to enter human cells, offering new insight into why some people are more vulnerable to COVID-19 than others.
“We’ve known that the virus SARS-CoV-2 enters the body through the respiratory tract, with the nose being a key entry point. What’s new — and surprising — is that bacteria in our noses can influence the levels of proteins that the virus uses to infect cells,” said Cindy Liu, associate professor of environmental and occupational health at the GW Milken Institute School of Public Health.
Higher Gene Expression of Viral Entry Proteins Increases COVID-19 Infection Risk
In the study, Liu and her team analyzed nasal swab samples from over 450 people, including some who later tested positive for COVID-19. They found that those who became infected had higher levels of gene expression for two key proteins — ACE2 and TMPRSS2. ACE2 allows the virus to enter nasal cells, while TMPRSS2 helps activate the virus by cleaving its spike protein.
Those with high expression for these proteins were more than three times as likely to test positive for COVID-19, while those with moderate levels had double the risk. The study also found that people who became infected had more unstable levels of gene expression, with the sharpest increases just days before testing positive, suggesting rising expression levels may signal increased vulnerability to the virus.
Notably, while women generally had higher gene expression levels of these proteins — consistent with previous studies showing higher COVID-19 infection rates in women — men with higher levels were more likely to get infected, indicating elevated protein levels may present a greater risk for men.
Nasal Bacteria May Play a Role in COVID-19 Risk
To understand what could impact the expression levels of these viral entry proteins, the researchers turned to the nasal microbiome — the diverse community of bacteria that naturally reside in the nose. They found that certain nasal bacteria may affect the expression levels of ACE2 and TMPRSS2, influencing the respiratory tract’s susceptibility to COVID-19.
The study identified three common nasal bacteria — Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis/nonliquefaciens — that were linked to higher expression levels of ACE2 and TMPRSS2 and increased COVID-19 risk. On the other hand, Dolosigranulum pigrum, another common type of nasal bacteria, was connected to lower levels of these key proteins and may offer some protection against the virus.
“Some bacteria in your nose may be setting the stage — or even holding the door open — for viruses like SARS-CoV-2 to get in,” said Daniel. Park, a senior research scientist at GW and the first author of the study.
While some of the high-risk bacteria were less common, 20% of participants carried enough S. aureus to nearly double their risk for having elevated ACE2 and TMPRSS2 expression, making it a major nasal microbiome risk factor for increasing individuals’ risk for COVID-19 infection.
Why This Matters
The findings offer new potential ways to predict and prevent COVID-19 infection. The study suggests that monitoring ACE2 and TMPRSS2 gene expression could help identify individuals at higher risk for infection. The research also highlights the potential of targeting the nasal microbiome to help prevent viral infections.
“We’re only beginning to understand the complex relationship between the nasal microbiome and our health,” said Liu. “This study suggests that the bacteria in our nose — and how they interact with the cells and immune system in our nasal cavity — could play an important role in determining our risk for respiratory infections like COVID-19.”
The team plans to explore whether modifying the nasal microbiome, such as through nasal sprays or live biotherapeutics, could reduce the risk of infection — potentially paving the way for new ways to prevent respiratory viral infections in future pandemics.
The study, “The Nasal Microbiome Modulates Risk for SARS-CoV-2 Infection,” was published April 9 in the journal EBioMedicine. The research was supported by the GW Milken Institute School of Public Health and by the National Institutes of Health.