According to a new study led by Weill Cornell Medicine and NewYork-Presbyterian, certain gut-dwelling fungi flourish in severe cases of Covid-19, exacerbating the extreme inflammation that causes the disease as well as triggering long-term changes in the immune system. . This research points to a subgroup of individuals who may benefit from specific, yet-to-be-defined treatments.
According to a new study led by Weill Cornell Medicine and New York-Presbyterian, certain gut-dwelling fungi flourish in severe cases of COVID-19, exacerbating the severe inflammation that causes the disease. It also triggers long-term changes in the immune system.
This research points to a subgroup of individuals who may benefit from specific, yet-to-be-defined treatments.
Using patient samples and preclinical models, the researchers found that the proliferation of fungi in the gut, specifically the Candida albicans yeast strain, increases immune cells whose actions can exacerbate lung injury.
Their findings, published in Nature Immunology on October 23, also show that patients maintain an enhanced immune response and immune memory against the fungus for up to a year after resolution of SARS-CoV-2 infection. Senior author Dr. Ilian Iliev, associate professor of immunology in the Department of Medicine, co-director and member of the Microbiome Core Lab
Accordingly, the research reveals a new dimension of complex pathology due to severe Covid-19. Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine. “Severe and prolonged COVID-19 is not thought to involve fungal overgrowth in the gut, which, in addition to the virus, can affect the patient’s immune system,” he said.
An immunologist who studies the microbiome and chronic inflammatory conditions targeting the gastrointestinal tract, Dr. Ilive, was responsible for COVID-19 during the pandemic. As researchers have gotten a better handle on new viral infections, it has become clear that in Covid-19, as in inflammatory bowel disease, the body’s own inflammatory immune response causes damage.
To investigate this defective immune response, Dr. Ilive and Dr. Takato Kusakabe, a postdoctoral fellow and first author of the study, worked with several collaborators to develop mouse models to study three large clinical cohorts of COVID-19 patients. Study the disease.
He collaborated with members of the Weill Department of Pathology and Laboratory Medicine at Weill Cornell Medicine, including Drs. Stephen Josephovitz, Dr. Mirella Salvatore, Dr. Melissa Cushing, Dr. Lars Westblad and Dr. Includes Adolfo García-Sastre. , professors were involved. of microbiology and director of the Global Health and Emerging Pathogens Institute at the Icahn School of Medicine at Mount Sinai.
The team first made the connection when analysis of blood samples from patients with severe COVID-19 at NewYork-Presbyterian/Weill Cornell Medical Center revealed the presence of antibodies designed to attack a common fungus in the gut.
The researchers then found that the population of yeast, and one species in particular, Candida albicans, increased in patients’ guts during severe COVID-19.
When they looked at the patient’s immune system, the researchers found a parallel increase in immune cells called neutrophils. In severe COVID-19, excessive numbers of neutrophils appear in the lungs, where their activity worsens the inflammatory response already damaging these organs.
Turning to preclinical models, the investigators found that mice inoculated with fungi from patients with severe COVID produced more neutrophils in their blood and lungs, and were less likely to develop increased inflammation when infected with SARS-CoV-2. There were signs. However, giving them an antifungal drug reduced these effects.
In the patients’ blood samples, the researchers also found evidence of persistent changes in the immune system that they believe are related to a condition called prolonged COVID-19, in which symptoms persist, or new symptoms develop after the infection clears.
When the team tested the patients’ blood a year later, they found that the anti-fungal antibodies were still present. Additionally, when they looked at the stem cells that give rise to neutrophils, the researchers found that these progenitors were engineered to respond to the fungus.
They found that an immune protein called IL-6 that this fungus induces strengthens both neutrophils and antibodies.