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- Long COVID is a condition that involves persistent symptoms for weeks or months after initial infection with SARS-CoV-2, the coronavirus that causes COVID-19.
- People with a less diverse microbiome in their intestines were more likely to have lingering symptoms after coronavirus infection.
- The exact cause of long COVID — and why some people may be at higher risk of developing it — is not known.
The composition of the gut microbiome is “strongly” linked with long-COVID symptoms months a person recovers from their initial infection, a new study shows.
This suggests “that the human gut microbiome may play an important role in development of” long COVID, also known as post-acute sequelae of SARS-CoV-2 infection, or PASC, the researchers write.
They also suggest that analyzing which bacteria, fungi, and other microbes are present in a person’s intestines — known as microbiome profiling — could help determine which people are more at risk of developing this condition.
The study was published Jan. 26 in the journal Gut.
Exact cause of long COVID unknown
Long COVID is a condition that involves persistent symptoms for weeks or months after initial infection with SARS-CoV-2, the coronavirus that causes COVID-19.
Fatigue, shortness of breath, chest pain, loss of smell, and “brain fog” are some of the most commonly reported symptoms.
This condition is not limited to people who have had severe COVID-19. It can also occur in those who had mild symptoms initially, including children and adolescents.
The exact cause of long COVID — and why some people may be at higher risk of developing it — is not known.
Several possible explanations have been proposed for this condition, including an exaggerated immune response, ongoing inflammation, cell damage, and physiological effects of severe illness.
In addition, a recent study identified four factors potentially involved in causing long COVID — type 2 diabetes, reactivation of the Epstein-Barr virus in the body, the presence of antibodies that mistakenly attack a person’s cells, and the presence of coronavirus RNA in the blood.
Mahmoud A. Ghannoum, PhD, director of the Center for Medical Mycology at University Hospitals Cleveland Medical Center, said earlier research — such as a study published last year in Gut — has also connected the gut microbiome to the severity of COVID-19.
In those studies, patients with more severe COVID-19 tend to have a decreased microbial diversity in the intestines, he said.
In addition, he said they often have a reduction in beneficial microbes that help support the immune system and an increase in pathogenic microbes, those that “cause trouble.”
“What this [new] study did is extend this observation to say that the changes in the composition of the microbiome could affect how we respond to long-term [after COVID-19],” said Ghannoum, also a professor of dermatology and pathology at the Case Western Reserve University School of Medicine.
In the new study, Hong Kong researchers looked not only at the link between the gut microbiome and long-COVID symptoms, but also the connection with the types of symptoms people experienced and the severity of their initial illness.
The study included 106 people who had been hospitalized with COVID-19. The majority of these had mild to moderate illness, although some had more severe COVID-19.
Researchers asked people 3 and 6 months after their initial illness whether they were experiencing any long-COVID symptoms. Over 80 percent said yes at both time points.
Fatigue, poor memory, hair loss, anxiety, and difficulty sleeping were the most common symptoms reported by people at 6 months.
The researchers also analyzed the gut microbiomes of 68 of these people using stools samples. Fifty of these people had long-COVID symptoms.
Some of the 68 people also completed a 6-minute walk test at their 6-month follow-up visit to assess their aerobic capacity and endurance.
At 6 months, there were no significant differences in other factors that could impact the microbiome, such as age, gender, underlying health conditions, use of antibiotics or antiviral drugs, and COVID-19 severity, between people with and without long COVID.
In addition, for a comparison group, researchers recruited 68 patients who hadn’t had a coronavirus infection. They analyzed the gut microbiome for some of these individuals.
Dr. David Strain, chair of BMA Board of Science and clinical senior lecturer and honorary consultant at the University of Exeter Medical School, said in a statement that the study was interesting but more study is needed to confirm whether these findings would apply to other groups.
“This finding is consistent with several existing hypotheses that long COVID may be associated with a small quantity of residual virus in the immuno-privileged tissue (i.e., the regions of the body such as the gut, that the protection of our antibodies doesn’t reach),” Strain said.
“It is important to clarify that there are some substantial potential confounders in this study,” he added. “Notably that this is in a Hong Kong population that have a significantly different diet to the U.K. population and are have been demonstrated to have substantial differences In their dominant gut species.”
Balanced gut microbiome was beneficial
Researchers found no link between a person’s initial viral load and whether they went on to develop long COVID. They also found no link between the gut microbiome and the severity of a person’s illness.
However, they did find that people with long COVID had “distinct” differences in their gut microbiome than individuals who hadn’t had a coronavirus infection.
Long-COVID patients had a less diverse gut microbiome than non-COVID patients. At 6 months, people with long COVID also had fewer “friendly” bacteria and a greater abundance of “unfriendly” bacteria than people who hadn’t had COVID-19.
What this research shows, said Ghannoum, is that “if you have a microbiome that is not balanced — what we call dysbiosis — the likelihood of having these symptoms will be much higher.”
In contrast, people who didn’t develop long COVID had fewer changes in their gut microbiome, and this “recovered completely by 6 months,” the authors found.
In fact, the gut microbiome of people who didn’t develop long COVID was similar to the non-COVID patients.
“If you have a more balanced microbiome at the beginning, you will be able to fight these symptoms,” said Ghannoum, “or you will at least recover much faster.”
“So in a way, [this study] is telling us that having a balanced microbiome is really an advantage,” he said.
Researchers also looked at whether the composition of the gut microbiome was associated with different categories of long-COVID symptoms, such as respiratory, neurological, gastrointestinal, muscle- and joint-related, and fatigue.
The results suggest that “different [gut] microbial patterns may contribute to development of different [long-COVID] symptoms,” they wrote. “Thus the microbiome could potentially serve as a proxy for prediction of development of specific post-acute COVID-19 symptoms.”
For example, they found that higher levels of certain “unfriendly” microbes were linked with persistent respiratory symptoms. People with long COVID also had lower levels of several bacteria species that the authors say are known to be beneficial for immunity.
In addition, several “unfriendly” bacteria species were more common in people with long COVID who performed poorly on the 6-minute walk test.
This is an observational study, so it can’t show whether long-COVID symptoms are the result of the gut microbiome changes or the other way around.
Ghannoum said the study also had several limitations, including its small size and that researchers didn’t measure other factors that could impact the gut microbiome, such as diet, lifestyle, and other medications.
Ways to keep the gut microbiome healthy
Although more research is needed, Ghannoum said this study is a reminder of the importance of the gut microbiome for our health, including for how we respond to viral infections.
“The fact that having a balanced gut microbiome resulted in less [long COVID] highlights that we should take the necessary steps to ensure that we have a balanced microbiome,” he said.
Microbiome research has already identified several ways in which people can improve their gut microbiome — all things that can also improve overall health.
A key one, said Ghannoum, is eating a healthy diet, one that is high in fiber, plant polyphenols (found in berries, nuts, vegetables, coffee, and tea), and unsaturated fats such as olive and sunflower oils.
Also, people should avoid eating excess saturated fats, refined sugars, and artificial sweeteners.
“In addition to diet,” said Ghannoum, “you have to follow a lifestyle which helps balance your gut, including exercise, sleep, and reduction of stress.”
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