Inflammatory Response in Severe COVID Linked to Elevated Gut Fungi Levels
New research suggests that an overabundance of certain fungi in the gut may be a contributing factor to the excessive inflammation seen in severe cases of COVID-19 and in individuals with long COVID.
This study, published in Nature Immunology, highlights the potential for antifungal treatments to offer relief to critically ill COVID-19 patients.
Inflammation is a key driver of severe COVID-19 cases, and this study sheds light on a potential mechanism involving fungal imbalance that may have been previously overlooked. While bacteria make up a significant portion of the microbiome, research has shown that fungi, known as the mycobiota, also interact with the immune system.
Earlier studies have demonstrated that individuals with COVID-19 often exhibit altered microbial compositions in their guts and compromised protective barriers, potentially allowing harmful pathogens to enter the bloodstream. Additionally, some severely ill COVID-19 patients have developed dangerous fungal infections in their lungs.
To delve deeper into the connection between the mycobiota and COVID-19, researchers led by immunologist Iliyan Iliev at Weill Cornell Medicine in New York City examined blood samples from 91 hospitalized individuals with COVID-19.
Nearly three-quarters of these patients had severe cases, requiring substantial oxygen supplementation or invasive mechanical ventilation. In comparison to a control group of 36 individuals who had never tested positive for the virus, those with severe COVID-19 produced approximately four times as many antibodies against three common fungal species found in the gut, including Candida albicans.
Elevated antibody levels indicated higher fungal quantities in these individuals. Furthermore, fecal samples collected in early 2021 from 10 COVID-19 patients revealed higher overall levels of gut fungi, particularly Candida species, relative to 10 healthy individuals. In these cases, the abundance of Candida correlated positively with disease severity. Notably, certain fungal species, particularly C. albicans, have been shown to activate the immune system.
In a subset of severe COVID-19 cases, the number of antibodies against C. albicans was associated with the presence of neutrophils, a type of immune cell capable of triggering inflammation.
In an experimental model, mice were infected with C. albicans from severe COVID-19 patients and subsequently exposed to SARS-CoV-2. This led to a higher influx of neutrophils into the mice’s lungs and an increased inflammatory response compared to mice infected with SARS-CoV-2 alone. Administering an antifungal drug to these mice reduced both the number and activity of neutrophils.
The study also revealed that individuals with severe COVID-19 maintained elevated levels of antibodies against C. albicans and neutrophil precursors prepared to combat fungi long after recovering from the disease, in some cases up to a year later. These findings suggest that changes in the mycobiota during a SARS-CoV-2 infection may contribute to the inflammation associated with long COVID.
According to Aran Singanayagam, a respiratory immunologist at Imperial College London, there are several theories regarding the triggers of persistent COVID-19 symptoms. One prominent theory revolves around microbial dysbiosis in either the gut or the lungs, and this study provides further support for this notion.
Researchers emphasize the need for additional investigations to fully understand the link between gut fungi and COVID-19. It remains uncertain whether the observed mycobiota changes in COVID-19 patients were a result of the disease or if they preexisted, potentially making individuals more susceptible.
If future studies unravel the underlying mechanisms, existing antifungal treatments could be repurposed to aid COVID-19 patients. Iliyan Iliev hopes that this research will encourage a broader consideration of common biological factors across various diseases and how they can be leveraged for therapeutic interventions.
