Why Do Some People Develop Severe COVID Symptoms From Novel Coronavirus?

Nasal microbiota holds clues to who will develop COVID symptoms from the novel coronavirus.

The microbiota in the nose and upper throat likely contains biomarkers for assessing how sick a person infected with SARS-CoV-2 can become and for developing new treatment strategies to improve their outcomes, researchers say.

This nasopharyngeal microbiota is generally considered a first-line protection against viruses, bacteria, and other pathogens that invade these natural passageways, says Dr. Sadanand Fulzele, a geriatric researcher in the Department of Medicine of the Medical College of Georgia at Augusta University.

Clear patterns emerged when the researchers examined the microbiota of 27 individuals aged 49 to 78 who were negative for the virus, 30 who were positive but had no symptoms, and 27 who were positive with moderate symptoms that did not require hospitalization, report them in the journal Diagnostics.

“Millions of people get infected and relatively few of them get symptoms. This could be one of the reasons,” says Dr. Ravindra Kolhe, director of MCG’s Georgia Esoteric and Molecular Laboratory, or GEM Lab. who has conducted more than 100,000 COVID tests.

Dr Sadanand Fulzele (left) and Dr. Ravindra Kolhe. Credit: Michael Holahan, Augusta University

The most significant changes were in those who were symptomatic, including about half of the patients who didn’t have enough microbiota to sequence them, says corresponding author Fulzele.

They were surprised to find these “low levels” of bacteria in the nasopharyngeal cavity of symptomatic individuals versus only two and four individuals in the negative and positive groups with no symptoms, respectively. The vast majority of positive individuals with no symptoms still had sufficient microbiota, notes lead author Kolhe.

“We don’t know which came first, the disease or the eradication of the microbiota,” Fulzele says. Runny noses and sneezing may have been the cause of the loss, an already significantly lower number of bacterial residents may have increased the individual’s risk of developing these types of symptoms, or the virus may have changed the landscape, says Fulzele, who suspects it may have caused the disease. last one.

Based on experience with microbiota in the GI tract, Kolhe thinks the different microbiota content and size is another good guess and they’d both like a definitive answer. “Right now we don’t have enough data,” says Kolhe.

They also found differences in the type of bacteria, although the researchers note that the function of some of the bacteria they found is not well understood.

As the name of the virus and nearly two years of experience with it indicate, a major method of transmission of severe acute respiratory syndrome is coronavirus 2, or SARS-Cov-2, when a person coughs, sneezes, or even talks, and droplets that become aerosols referred to as carrying the virus through the air and into another person’s nose or mouth.

Those 65 and older and/or with underlying health conditions such as hypertension and diabetes are considered to be at increased risk of hospitalization and death from the infection, so they decided to look at the microbiota in the upper respiratory system, the nasopharynx of older individuals.

The moist, mucus-producing lining of this area acts as a natural barrier against invaders, and a significant replenishment of immune cells is also present, Fulzele says, and their response to respiratory viruses is key.

The area is also abundant with ACE-2 receptors, which the spiny virus binds to, and Kolhe says it’s an important landing site for this virus.

Their new findings indicate that the altered microbiota in the symptomatic patients affected their immune response to the virus, Kolhe and Fulzele say.

The symptomatic individuals had significantly higher levels of two bacterial species, including Cutibacterium, which is commonly found on the skin and associated with acne, as well as heart infection and shoulder infections after surgery. Conversely, there was a significantly lower presence of a handful of other, not well-studied bacteria.

The microbiota of both infected groups, symptomatic and asymptomatic, had high levels of bacteria such as cyanobacteria, also called blue-green algae, which can be found in contaminated water, but are a common inhabitant of the human microbiome that appears to play a role. play in regulating the immune response. These bacteria usually enter the body through mucosal surfaces, such as those in the nose, and are known to cause pneumonia and liver damage. Those who were symptomatic had twice as much of this bacteria as their asymptomatic counterparts.

Fulzele notes that between the asymptomatic and symptomatic there was no significant change in microbiota diversity — just those big differences in volume — but they did see many individual bacteria move up and down in number.

For example, their graph of the numbers of another water-loving bacterium, Amylibacter, looked like stair steps as it went from negative to positive with individuals with symptoms, while there was a downward trend in a handful of other bacteria.

While the relationship between the nasopharyngeal microbiota and the severity of COVID-19 remains unknown, their research points to a “strong association” between the nasal microbiota, SARS-CoV-2 infection and severity, they write.

Their analysis was done before current virus variants surfaced, but the researchers say the differences in the microbiota are likely to hold true for these as well, and they’ve already started that analysis.

Larger studies are needed to ensure the clear patterns they found hold up, the researchers say. They are preparing a grant application that makes a larger study possible and they are looking for other test locations that want to become partners. By using the same nasopharyngeal swab used for many COVID testing, a microbiota analysis could be performed at the same time as testing, they say.

They note the striking contrast created in nearly two years of experience with the virus, with the majority of those infected being asymptomatic or experiencing mild symptoms like the common cold, while others develop severe viral pneumonia, require hospitalization and die.

A handful of recent studies have now been published suggesting that the bacterial makeup of the nasal tract can have a “drastic” impact on the occurrence of respiratory infections and the severity of symptoms, they write. Some research has shown that the nasal microbiota can influence the viral load, immune response, and symptoms of a rhinovirus infection, which accounts for anywhere from 10-40% of colds.

A host of other conditions such as inflammatory bowel syndrome, stomach ulcers and viral diseases have been linked to significant changes in the microbiota of the gut, nose and oral cavity, they write.

Bacterial diversity in the microbiota is generally a good thing, and it’s something that naturally decreases with age, Fulzele says, and can also be harmed by habits like smoking and improved by people like eating a varied diet.

Reference: “Change in the nasopharyngeal microbiota profile in elderly patients with COVID-19” by Ravindra Kolhe, Nikhil Shri Sahajpal, Sagar Vyavahare, Akhilesh S. Dhanani, Satish Adusumilli, Sudha Ananth, Ashis K. Mondal, G. Taylor Patterson, Sandeep Kumar, Amyn M. Rojiani, Carlos M. Isales and Sadanand Fulzele, September 5, 2021, Diagnostics.
DOI: 10.3390/diagnostics11091622

The work was supported in part by the National Institutes of Health.