Human gut microbiome picture showing a variety of microbes including fungi such as Candida albicans
Credit: Larry Washburn / Getty Images

Research led by Weill Cornell Graduate School of Medical Sciences shows that certain species of gut fungi, notably Candida albicans, increase in numbers during serious COVID-19 infection and appear to contribute to the excessive and damaging inflammation seen in these patients.

High levels of immunoglobulin G (IgG) antibodies against fungi such as C. albicans and reprogramming of granulocyte myeloid progenitor cells were seen in patients with severe COVID-19 for as long as a year after the initial infection with SARS-CoV-2.

When model mice were colonized with samples of these fungi from patients with COVID-19, they also had an excessive immune reaction during SARS-CoV-2 infection showing high neutrophil levels and associated lung damage.

“Studies have reported substantial involvement of the GI tract in the pathophysiology of several inflammatory diseases, including severe COVID-19,” write Iliyan Iliev, an associate professor at Weill Cornell Medicine, and colleagues in Nature Immunology.

“Patients with COVID-19 present with altered gut microbial composition and gut barrier dysfunction, which could increase the translocation of bacterial products and toxins into the circulation and exacerbate the inflammatory response systemically and at distal sites.”

Much research has been and is being carried out on the gut microbiome and its effect on different diseases. Much of the attention has focused on gut bacteria, but fungal species also play an important role.

In this study, Iliev and colleagues analyzed stool samples from patients with serious COVID-19 to assess microbial composition and found abnormally high levels of C. albicans and other gastrointestinal-related fungal species (not common inhaled airborne species), as well as an associated high level of immune reactivity to these fungi.

Treatment with the drug tocilizumab, which targets the interleukin-6 (IL-6) pathway, reduced levels of C. albicans immune reactivity in both humans and mice.

“IL-6 is a pleiotropic cytokine with a variety of roles in the immune system that has been linked to tissue damage and immune cell activation in severe COVID-19,” explain the authors. “Specifically, we found that systemic and lung neutrophilia prompted by intestinal C. albicans expansion was dependent on the IL-6 receptor.”

Although it is not the only cause of inflammation in these patients, targeting any excess inflammation can be helpful for COVID-19 patients. Testing for antifungal antibodies could help tailor therapy and highlight who may benefit from antifungal or specific anti-inflammatory therapies such as those targeting the IL-6 pathway.

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