New Study Finds Imbalance of Gut Fungi Could Contribute to Severe COVID-19 and Long COVID
In a recent study published in Nature Immunology, researchers have found that an imbalance of fungi in the gut could potentially contribute to excessive inflammation in individuals with severe COVID-19 or long COVID. The study reveals that people with severe COVID-19 had elevated levels of a specific fungus that can activate the immune system and induce long-lasting changes.
The findings raise the possibility that antifungal treatment could provide relief to critically ill individuals with COVID-19. “We know inflammation is driving severe disease,” says Martin Hönigl, a clinical mycology researcher at the Medical University of Graz in Austria. This study provides a potential mechanism of disease-causing inflammation that may have been previously overlooked.
Trillions of microorganisms, including fungi, reside in and on our bodies, playing various roles in our health and well-being. Previous research has shown that the fungal portion, called the mycobiota, interacts with the immune system. It has also been observed that many people with COVID-19 have disrupted gut microbial compositions and compromised protective barriers, potentially allowing pathogens to enter the bloodstream. Some individuals with severe COVID-19 have even developed dangerous fungal infections in their lungs.
To further investigate the link between the mycobiota and COVID-19, a team of researchers examined blood samples from 91 hospitalized individuals with the disease. The results revealed that people with severe COVID-19 produced about four times as many antibodies against specific fungal species commonly found in the gut, including Candida albicans, compared to individuals who had never tested positive for SARS-CoV-2. Faecal samples collected from COVID-19 patients also showed higher overall levels of gut fungi, especially Candida species, indicating a positive correlation with disease severity. Previous research has shown that the presence of certain fungal species, including Candida albicans, can activate the immune system.
In a subset of people with severe COVID-19, the number of antibodies against Candida albicans was also linked to the number of immune cells called neutrophils, which can trigger inflammation. When mice were infected with Candida albicans extracted from individuals with severe COVID-19 and then infected with SARS-CoV-2, more neutrophils invaded their lungs and activated an inflammatory response compared to mice infected with SARS-CoV-2 alone. These findings suggest that antifungal drugs could potentially lower the number and activity of neutrophils.
The study also discovered that individuals with severe COVID-19 continued to have elevated levels of antibodies against Candida albicans and neutrophil precursors primed to counter fungi long after recovering from the disease. This implies that changes in the mycobiota during a SARS-CoV-2 infection may contribute to the inflammation associated with long COVID.
Aran Singanayagam, a respiratory immunologist at Imperial College London, states that there are several theories about what might trigger persistent symptoms after COVID-19, and microbial dysbiosis is one major theory. Further research is needed to establish the link between gut fungi and COVID-19, including whether the observed changes in the mycobiota resulted from the disease or preceded it.
If future studies reveal more about the underlying mechanisms, existing antifungal treatments could potentially be repurposed to help individuals with COVID-19. The hope is that this research will prompt further exploration of common biological factors seen in different diseases and how they can be leveraged for treatment.