science

Coronavirus infects cells in the mouth, causing oral symptoms like taste loss, study shows


SARS-CoV-2, the coronavirus that causes Covid-19, infects saliva and cells in the mouth, a new study shows.

US researchers have found evidence that salivary glands are one area in the mouth where the deadly virus infects our cells. 

SARS-CoV-2 infection in the mouth accounts for the oral symptoms people with Covid-19 have been experiencing, such as taste loss, dry mouth and blistering, they believe. 

The mouth may also play a role in transmitting SARS-CoV-2 to the lungs or digestive system via saliva laden with virus from infected oral cells, the experts think.

Prior evidence has already suggested Covid-19 spreads via mouth and nose secretions, including saliva, according to the World Health Organisation (WHO). 

SARS-CoV-2 infects the oral cavity and saliva, say researchers at the National Institute of Dental and Craniofacial Research

SARS-CoV-2 infects the oral cavity and saliva, say researchers at the National Institute of Dental and Craniofacial Research

‘By revealing a potentially underappreciated role for the oral cavity in SARS-CoV-2 infection, our study could open up new investigative avenues leading to a better understanding of the course of infection and disease,’ said study author Blake M. Warner at the National Institute of Dental and Craniofacial Research in the US

‘Such information could also inform interventions to combat the virus and alleviate oral symptoms of Covid-19.’     

It’s well known that the upper airways and lungs are primary sites of SARS-CoV-2 infection.  

But there have already been ‘clues’ that the virus can infect cells in other parts of the body, such as the digestive system, blood vessels, kidneys and, as this study shows, the mouth.

The potential of the virus to infect multiple areas of the body might help explain the wide-ranging symptoms experienced by Covid-19 patients.

Researchers already know that the saliva of people with Covid can contain high levels of SARS-CoV-2. 

Studies also suggest that saliva testing is nearly as reliable as deep nasal swabbing for diagnosing the disease. 

Pictured. invasive nasal swabbing currently in operation to diagnose people with Covid-19

Pictured. invasive nasal swabbing currently in operation to diagnose people with Covid-19 

COVID-19 SYMPTOMS 

Main symptoms of Covid-19 

The most common symptoms of COVID-19 are:

– Recent onset of a new continuous cough

– A high temperature

– Loss of, or change in, normal sense of taste or smell (anosmia)

Other symptoms Covid-19  

– Aches and pains

– Sore throat

– Diarrhoea

– Conjunctivitis (sore, red eyes) 

– Headache 

– A skin rash/discolouration of fingers or toes 

These other symptoms are less common. 

Public Health England says people only need to be tested if they also have at least one of the main symptoms. 

What scientists don’t entirely know, however, is where SARS-CoV-2 in the saliva comes from. 

In people with Covid who have respiratory symptoms like coughing, virus in saliva possibly comes in part from ‘nasal drainage’ or sputum coughed up from the lungs. 

But that may not explain how the virus gets into the saliva of people with Covid who lack respiratory symptoms. 

This, therefore, suggests some sort of infection local to the mouth.  

‘Based on data from our laboratories, we suspected at least some of the virus in saliva could be coming from infected tissues in the mouth itself,’ said Warner. 

To explore this possibility, the researchers surveyed oral tissues from healthy people to identify mouth regions susceptible to SARS-CoV-2 infection. 

After more than a year into the pandemic, it’s almost common knowledge how exactly the virus infects our cells.    

Angiotensin-converting enzyme 2 (ACE2) – an enzyme attached to the cell membranes of cells located in the arteries and lungs – is already known to be the ‘gateway’ for coronavirus infection.  

SARS-CoV-2 has a spike on the surface of its envelope called an S-protein which allows it to bind with the ACE2 receptor located on human cells.  

Once the spike has opened the door for the virus to enter the cell, the genetic material of SARS-CoV-2, its RNA, binds to myriad proteins and begins replicating. 

Researchers found RNA for two key entry proteins – known as the ACE2 receptor and the TMPRSS2 enzyme – was found in certain cells of the salivary glands and tissues lining the oral cavity. 

In a small portion of salivary gland and gingival (gum) cells, RNA for both ACE2 and TMPRSS2 was expressed in the same cells. 

This indicated increased vulnerability because the virus is thought to need both entry proteins to gain access to cells.

Illustration of SARS-CoV-2 virus binding to ACE2 receptors on a human cell, the initial stage of Covid infection

Illustration of SARS-CoV-2 virus binding to ACE2 receptors on a human cell, the initial stage of Covid infection

ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream

ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream

Once the researchers had confirmed that parts of the mouth are susceptible to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from people with Covid. 

In samples collected at National Institutes of Health (NIH) from Covid patients who had died, SARS-CoV-2 RNA was present in just over half of the salivary glands examined. 

In salivary gland tissue from one of the people who had died, as well as from a living person with acute Covid, the scientists detected specific sequences of viral RNA that indicated cells were actively making new copies of the virus.

This provided further evidence for infection in the mouth – salivary gland tissue to be exact. 

RNA for SARS-CoV-2 (pink) and the ACE2 receptor (white) was found in salivary gland cells, which are outlined in green

RNA for SARS-CoV-2 (pink) and the ACE2 receptor (white) was found in salivary gland cells, which are outlined in green

As well as finding evidence of oral tissue infection, those tissues appeared to be a source of the virus in saliva. 

In people with mild or asymptomatic Covid, cells shed from the mouth into saliva were found to contain SARS-CoV-2 RNA, as well as RNA for the entry proteins.

To determine if virus in saliva is infectious, the researchers exposed saliva from eight people with asymptomatic Covid – people with the illness showing no symptoms – to healthy cells grown in a dish. 

Saliva from two of the volunteers led to infection of the healthy cells, raising the possibility that even people without symptoms might transmit infectious SARS-CoV-2 to others through saliva.

Finally, to explore the relationship between oral symptoms and virus in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic Covid. 

Of the 27 people who experienced symptoms, those with virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might cause oral symptoms of Covid.

Overall, the findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection than previously thought.  

More research will now be needed to confirm the findings in a larger group of people and to determine the exact nature of the mouth’s involvement in SARS-CoV-2 infection and transmission within and outside the body.    

The study has been published in the journal Nature Medicine

ACE2 ENABLES CORONAVIRUS TO INFECT HEALTHY HUMAN CELLS

ACE-2 receptors are structures found on the surface of cells in the lungs and airways which work with an enyzme called ACE (angiotensin-converting enzyme) to regulate blood pressure.

Its exact function in the lungs is not well understood but studies suggest it is protective against lung damage and low levels of it can worsen the impact of viral infections.

Scientists say that the coronavirus enters the body through the ACE-2 receptor, which the shape of it allows it to latch on to.

This means that someone with more ACE-2 receptors may be more susceptible to a large viral load – first infectious dose of a virus – entering their bloodstream.

ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream, scientists say +7

ACE-2 receptors have a shape which matches the outside of the coronavirus, effectively providing it with a doorway into the bloodstream, scientists say

People who have higher than usual numbers of ACE-2 receptors may include those with diabetes or high blood pressure because they have genetic defects which make them produce more. Emerging evidence shows that smokers may also produce more.

High levels of ACE-2 receptors may also be protective, however.

They are thought to be able to protect the lungs during infection and a study on mice in 2008 found that mice which had ACE-2 blocked in their bodies suffered more damage when they were infected with SARS, which is almost identical to COVID-19.

Smoking has in the past been repeatedly linked to lower than normal levels of ACE-2 receptors, potentially increasing the risk of lung damage from COVID-19. 



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