Pathophysiology of Long COVID 2: The Microbiome

Pathophysiology of Long COVID 2: The Microbiome

Gut bacteria may play a role in managing symptoms. Earlier this year, a clinical study showed that patients with Long COVID considerably improved digestive and neurocognitive symptoms after taking capsules with live probiotic bacteria. These findings raise an intriguing question: how can bacteria ameliorate these symptoms?

Our body, particularly the mouth and gut, accommodates various living microorganisms that are beneficial (and sometimes harmful) for us. The role of this microbiome, which includes various species of bacteria, fungi, and viruses, is still not fully clear. However, some of the microorganisms in the gut are associated with various diseases like colorectal cancer, inflammatory bowel disease, diabetes, respiratory infections, and even Parkinson’s disease.

Several studies reported that gut microbiome might also contribute to the development of Long COVID symptoms, mainly due to a disturbed balance between good bacteria, such as probiotic bacteria, and harmful bacteria. Due to the infection, beneficial bacteria, which help maintain a healthy gut and support our immune system, decrease. These changes in the composition of gut bacteria due to SARS-CoV-2 can persist even up to one year after initial infection. Blood analysis of patients with COVID-19 showed that the imbalanced gut microbiome might cause life-threatening infections because bacteria from the gut might translocate to the bloodstream.

SARS-CoV-2 usually enters our body through the cells in the nose and throat. Research showed that bacteria were also changed in these areas during the infection, such as lowering of the number of beneficial probiotic bacteria. Similar alterations were also observed in the bacterial microbiome of the lower respiratory tract in patients with severe COVID-19 where more types of harmful bacteria were found than in healthy people.

The bacterial microbiome of Long COVID patients differs from healthy controls.

Potential mechanisms underlying gut health and Long COVID

The exact cause of Long COVID remains poorly understood but impaired gut health is one of the mechanisms thought to underlie this condition. One study reported that diarrhea during the initial infection could cause disorders in the digestive system and an imbalance in gut bacteria. Another study showed that in Long COVID patients with digestive problems, certain immune cells, specifically CD8+ and CD4+ T cells, become active not during acute disease but only when Long COVID symptoms are noticed. These immune cells could be associated with gut related Long COVID symptoms.

Although the primary target of SARS−CoV−2 are lung cells, the virus can also attack our digestive system and stay there for many months. The virus enters cells through a specific receptor on the cell surface and causes inflammation which further disturbs the balance between the good and bad bacteria. This, together with the viral infection, triggers the immune cells which produce substances called cytokines that cause inflammation. These changes can additionally disrupt the gut bacteria and worsen digestive symptoms. Especially for patients with long-lasting symptoms, digestive issues might occur because the virus stays in the gut and the ongoing imbalance of gut bacteria and inflammation keep disturbing the digestive tract.

SARS-CoV-2 can also damage or kill gut cells that form the protective lining inside the gut. Due to this, various substances, and microorganisms like fungi from the gut can enter the bloodstream which can cause sepsis in some cases. Research has shown that changes in the gut barrier happen early during the infection and can last over a lengthy period.


How can gut bacteria improve Long COVID symptoms?

In a study from Hong Kong, 463 patients with at least one Long COVID symptom received either a daily probiotic (a capsule containing live bacteria) or a placebo for 6 months. Those who received the therapy, reported significant improvements in digestive problems, fatigue, difficulty in concentrating, memory loss and general unwellness. For example, 70% of patients with digestive issues felt better after 6-month treatment with the probiotic compared with 54% of those treated with placebo. These digestive complaints included diarrhea, constipation, abdominal and epigastric pain, bloating, vomiting, and acid reflux.


Study En

Improving the gut microbiome of Long COVID patients can help with symptom management.


When the researchers checked their stools, patients receiving the probiotic had more different species of bacteria, more beneficial bacteria, and fewer harmful bacteria in the gut than patients receiving placebo. Further analyses also showed that this active bacteria product lessened inflammation and lowered the amount of the virus in the nose and throat.

The study tested one specific probiotic product only available in Hong Kong containing Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin. It was not tested whether the specific product helped patients or if any measures strengthening the gut microbiome would have the same effect. It is however known that a microbiome with high diversity of beneficial bacteria can have positive impact on overall health.

The gut microbiome can be strengthened through nutrition by:

  • at least 30g of fiber per day (for adults) by eating fruits, vegetables, whole grains, and legumes
  • foods high in probiotics such as yogurt or sauerkraut
  • high-quality probiotic supplements could have a strengthening effect