Tag: nasal lining

Certain Nasal Bacteria May Boost the Risk for COVID-19 Infection

Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

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 analysed 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.

Source: George Washington University

Specific Nasal Cells Protect against COVID in Children

Legend of spirals: This image highlights the appearance of nasal cultures from older adults, revealing distinct spiral-like patterns that were absent in cultures grown from children. Credit: University College London

Important differences in how the nasal cells of young and elderly people respond to the SARS-CoV-2 virus, could explain why children typically experience milder COVID symptoms, finds a new study led by researchers at UCL and the Wellcome Sanger Institute.

The study, published in Nature Microbiology, focused on the early effects of SARS-CoV-2 infection on the cells first targeted by the viruses, the human nasal epithelial cells (NECs).

These cells were donated from healthy participants, including children (0–11 years), adults (30–50 years) and, for the first time, the elderly (over 70 years).

The cells were then cultured to regrow into the different types of nasal cells. Using single-cell RNA sequencing techniques that enable scientists to identify the unique genetic networks and functions of thousands of individual cells, the team identified 24 distinct epithelial cell types. Cultures from each age group were then either mock-infected or infected with SARS-CoV-2.

After three days, the NECs of children responded quickly to SARS-CoV-2 by increasing interferon (the first line of anti-viral defence), restricting viral replication. However, this early anti-viral effect became less pronounced with age.

The researchers also found that NECs from elderly individuals not only produced more infectious virus particles, but also experienced increased cell shedding and damage.

The strong antiviral response in the NECs of children could explain why younger people typically experience milder symptoms. In contrast, the increased damage and higher viral replication found in NECs from elderly individuals could be linked to the greater severity of disease observed in older adults.

Project lead, Dr Claire Smith (Associate Professor at UCL Great Ormond Street Institute of Child Health), said: “Our research reveals how the type of cells we have in our nose changes with age, and how this affects our ability to combat SARS-CoV-2 infection. This could be crucial in developing effective anti-viral treatments tailored to different age groups, especially for the elderly who are at higher risk of severe COVID-19.”

Co-Senior author, Dr Kerstin Meyer (Wellcome Sanger Institute), said: “By carrying out SARS-CoV-2 infections of epithelial cells in vitro and studying the responses with single cell sequencing, we get a much more detailed understanding of the viral infection kinetics and see big differences in the innate immune response between cell types.”

Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in infected people over the age of 85 remains high, despite vaccination and improving treatment options.

The research underscores the importance of considering age as a critical factor in both research and treatment of infectious diseases.

Co-senior author, Dr Marko Nikolic (UCL Division of Medicine), said: “It is fascinating that when we take away immune cells from nasal samples, and are only left with nasal epithelial cells grown in a dish, we are still able to identify age-specific differences in our body’s response to the SARS-CoV-2 between the young and elderly to explain why children are generally protected from severe COVID-19.”

Dr Smith added: “Understanding the cellular differences at the initiation of infection is just the beginning. We now hope to investigate the long-term implications of these cellular changes and test therapeutic interventions using our unique cell culture model. This ‘gold-standard’ system is only possible with the support of our funders and the willingness of participants to provide their samples.”

The team suggest that future research should consider how ageing impacts the body’s response to other viral infections.

Source: University College London

Nose Picking Opens up a Pathway for Dementia-linked Bacteria

Photo by Ketut Subiyanto

In mice, researchers have shown that Chlamydia pneumoniae can travel through the olfactory nerve in the nose and into the brain, where it creates markers that are a tell-tale sign of Alzheimer’s disease. Damage from nose picking can make infection easier for C. pneumoniae.

The Griffith University study, published in the journal Scientific Reports, showed that C. pneumoniae used the nerve extending between the nasal cavity and the brain as an invasion path to invade the central nervous system. The cells in the brain then responded by depositing amyloid beta protein which is a hallmark of Alzheimer’s disease.

Professor James St John, Head of the Clem Jones Centre for Neurobiology and Stem Cell Research, is a co-author of the world first research.

“We’re the first to show that Chlamydia pneumoniae can go directly up the nose and into the brain where it can set off pathologies that look like Alzheimer’s disease,” Professor St John said. “We saw this happen in a mouse model, and the evidence is potentially scary for humans as well.”

The olfactory nerve in the nose is directly exposed to air and offers a short pathway to the brain, one which bypasses the blood-brain barrier. It’s a route that viruses and bacteria have sniffed out as an easy one into the brain.

The team at the Centre is already planning the next phase of research and aim to prove the same pathway exists in humans.

“We need to do this study in humans and confirm whether the same pathway operates in the same way. It’s research that has been proposed by many people, but not yet completed. What we do know is that these same bacteria are present in humans, but we haven’t worked out how they get there.”

There are some simple steps to look after the lining of your nose that Professor St John suggests people can take now if they want to lower their risk of potentially developing late-onset Alzheimer’s disease.

“Picking your nose and plucking the hairs from your nose are not a good idea”,” he said.

“We don’t want to damage the inside of our nose and picking and plucking can do that. If you damage the lining of the nose, you can increase how many bacteria can go up into your brain.”

Smell tests may also have potential as detectors for Alzheimer’s and dementia says Professor St John, as loss of sense of smell is an early indicator of Alzheimer’s disease. He suggests smell tests from when a person turns 60 years old could be beneficial as an early detector.

“Once you get over 65 years old, your risk factor goes right up, but we’re looking at other causes as well, because it’s not just age—it is environmental exposure as well. And we think that bacteria and viruses are critical.”

Source: Griffith University