Long COVID and Gut-Lung-Axis

Long COVID is a term for the long-term health consequences that can exist after an infection with SARS-CoV-2. Statistics indicate that 10 to 20% of people infected with the coronavirus suffer from it. The term encompasses symptoms that persist longer than four weeks after infection with the coronavirus, worsen, or emerge anew.

Complaints that still exist after three months and last or recur for at least two months are referred to as post-COVID syndrome. New research findings are shedding light on this condition and indicating possible therapies.

The focus is on the influence of the gut and lung microbiomes both on the acute course of a COVID-19 illness as well as on long COVID and the Long-COVID syndrome.

Corona has affected all of us in one way or another over the past years. Many were patients themselves or dealt with the disease as caregiving relatives. It has been shown that Corona affects not only the lungs but also the gastrointestinal area, including the stomach, intestines, and even the liver.

This is because the virus requires a specific receptor to enter the cells of our bodies, and these receptors are also found in the gastrointestinal tract. Thus, nausea, vomiting, loss of appetite, and diarrhea were common symptoms.

Digestive tract complaints can occur before or after respiratory symptoms in the course of a Corona infection, varying widely depending on the region. A meta-analysis from the first Corona wave found diarrhea in about 50% of the affected individuals in some regions and only 1 to 2% in others.

At the University of Graz in Austria, data from 405 patients were retrospectively analyzed, showing that approximately 25% exhibited gastrointestinal complaints.

Interestingly, during the first wave, diarrhea was associated with a better chance of survival, though this effect could not be confirmed in further analyses. Diarrhea during a Corona infection is usually mild, but significant inflammation in the intestine can be seen. In certain patient groups, the inflamed intestine can become a long-term problem.

At the University of Innsbruck in Austria, colonoscopies in patients with chronic inflammatory bowel diseases showed that viral antigens were present in the intestinal mucosa for a very long time, coinciding with the symptoms of the Post-COVID Syndrome.

This led many researchers to the idea that the gut microbiome might play a role in Corona. Data has shown a reduction in the diversity of the gut microbiome after a Corona infection, an increase in potential pathogens, and notably, a decrease in beneficial bacteria.

Such a pattern is known from many other diseases when the microbiome is damaged. In the case of COVID-19, damage to the microbiome is also obviously relevant for the therapeutic success of patients. In severe COVID cases, a massive damage to the microbiome that is still detectable after several months has been found.

There is a provable connection between a damaged microbiome and the occurrence of bacterial sepsis. If the viral infection was somewhat well survived, patients often face a bacterial infection afterwards.

Our lifestyle has a significant influence on the general state and resilience of the gut microbiome, both positively and negatively. It is known, for example, that many medications, such as proton pump inhibitors (stomach acid blockers), lead to a change in the gut microbiome. Data indicates that the risk of bacterial infections after a COVID-19 illness is higher if patients take proton pump inhibitors.

On the other hand, the microbiome can be positively influenced. Data from various countries, where fermented foods are consumed in particularly large amounts, show a low mortality rate after a COVID-19 illness.

One could assume that the microbiome was positively influenced by the diet in these countries, thus improving the body's defense capabilities.

How are the microbiome and the coronavirus connected? The connection is made through the so-called gut-lung axis. Just as in the intestine, we also have a microbiome in the lung. These two microbiomes are in relation and in intense exchange, where, for example, cells from the intestine circulate into the lung.

When looking at this at the molecular level, patterns found in the lung are very similar to those in the intestine. Changes in the microbiome in both organs are associated with increased inflammation and increased permeability of the tissues.

Therefore, there is a possibility to influence the lung through the gut. Evidently, something can be done through diet - although changing the diet in the face of an acute Corona illness probably comes too late. Here, stronger measures are needed to change the microbiome - such as with probiotics.

Current analysis data show that it is indeed possible to positively influence the lung by probiotic modulation of the gut microbiome.

To simulate our Western lifestyle, mice were fed a high-fat diet and made to inhale polluted air. Both of these actions damage the lung and the gut. However, mice that received a multispecies probiotic showed an improvement in the composition of the gut microbiome and a reduction in lung inflammation.

There are initial findings suggesting that viral diseases can have a less severe course under the use of probiotics. Data on different probiotic products show that they can reduce the number and severity of viral infections. This is explained by the reduction in the amount of virus and immunomodulation thanks to the beneficial probiotic bacterial strains.

Concrete results are already available for Corona, showing that the use of a multispecies probiotic can significantly improve inflammation values and relieve symptoms in the case of Corona.

Currently, two pilot studies are being conducted at the Medical University of Graz in Austria, examining the effect of probiotics on the course of an acute Corona infection and on the gut-lung axis in the Long-COVID syndrome. Initial indications suggest that the course of a disease can be positively changed by taking probiotics, i.e., by modulating the gut and lung microbiomes, especially due to the bacterial strains specifically contained in the probiotic.

These strains work against various viruses, thus promoting the important diversity of the gut microbiome to a particularly high degree. For the treatment of the Long-COVID syndrome, which will challenge physicians and patients in the coming years, these data show encouraging trends.

Results suggest that lung function and the fatigue syndrome can be improved with a multispecies probiotic. This gives patients hope and a better quality of life.