"The groundwork of all happiness is health." - Leigh Hunt

Long-lasting effect of gut fungi on the immune response to acute COVID-19

According to a brand new study led by investigators at Weill Cornell Medicine and New York Presbyterian, certain fungi that live within the gut flourish in severe cases of COVID-19, which may exacerbate the excessive inflammation that drives the disease. while also causing lasting changes within the immune system. . This finding identifies a bunch of patients who may profit from specialized, but as yet undefined, treatments.

Using patient samples and clinical samples, the research team determined that the expansion of fungi within the intestinal tract, particularly yeast strains, stimulates a rise in immune cells whose functions can exacerbate lung damage. . Their findings, published Oct. 23, also show that patients maintain immune responses and immune memory against these fungi for as much as a 12 months after resolution of SARS-CoV-2 infection. The research reveals a brand new dimension of the complex pathology brought on by severe COVID-19, in keeping with senior creator Dr. Ilian Elif, an associate professor of immunology within the Department of Medicine, co-director of the Microbiome Core Lab and a member. Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

“Severe and prolonged COVID-19 was not thought to involve a fungal overgrowth in the gut that could affect the patient's immune system in addition to the virus,” he said.

Dr. Alev, an immunologist who studies the microbiome and chronic inflammatory conditions targeting the gastrointestinal tract, was drawn to COVID-19 in the course of the pandemic. As researchers got a greater handle on latest viral infections, it became clear that the body's own inflammatory immune response was causing damage, as in inflammatory bowel disease in COVID-19.

To investigate this misguided immune response, Dr. Alioff and Dr. Takato Kusakabe, a postdoctoral fellow and first creator of the study, worked with several colleagues to acquire three large clinical cohorts of COVID-19 patients and a worked to develop the mouse model. disease. He collaborated with members of the Weill Department of Medicine and Weill Cornell Medicine's Department of Pathology and Laboratory Medicine, including Dr. Stephen Josefutz, Dr. Mariela Salvatore, Dr. Melissa Cushing, Dr. Lars Westblade, and Dr. Adolfo Garcia. Sastre, professor of microbiology and director of the Global Health and Emerging Pathogens Institute on the Icahn School of Medicine at Mount Sinai.

How does gut fungus damage the lungs?

The team first made the connection when evaluation of blood samples from patients at New York-Presbyterian/Weill Cornell Medical Center diagnosed with severe COVID-19 revealed the presence of antibodies to a fungus common within the gut. were designed to attack. The researchers then found that the population of yeast, and one species specifically, increased in patients' guts during severe COVID-19.

When they checked out the patients' immune systems, the researchers found a parallel increase in immune cells called neutrophils. In severe COVID-19, large numbers of neutrophils appear within the lungs, where their activation worsens the inflammatory response that already damages these organs.

Turning to clinical models, the investigators found that mice with severe COVID-19 developed the fungus, produced more neutrophils of their blood and lungs, and when infected with SARS-CoV-2. So the intensity of inflammation increases in them. However, giving them an antifungal drug reduced these effects.

The immune system remembers.

From throughout the patients' blood samples, the researchers also uncovered evidence of persistent changes within the immune system that they've long believed to be related to a condition referred to as COVID-19, during which Symptoms persist after the infection clears, or latest ones develop.

When the team tested the patients' blood as much as a 12 months later, they found that the antifungal antibodies were still present. Also, after they checked out the stem cells that give rise to neutrophils, the researchers found that these progenitors were primed to answer the fungus. They found that an immune protein called IL-6, which this fungus induces, appears to stimulate each neutrophils and antibodies.

Further experiments showed that blocking IL-6 in patients or mice reduced this immunological memory, eliminating the presence of neutrophils and antibodies.

While these findings shouldn't have immediate implications for the treatment of acute or chronic COVID-19, they suggest latest opportunities for Taylor therapy, in keeping with Dr. Aliff. For example, antifungal antibodies could potentially function a marker to discover patients who may profit from a therapy that targets the fungus or an immunological response induced by it. Changes Or, assuming further research supports it, the presence of antibodies may indicate that somebody could also be in danger for long-term exposure to COVID-19. The team's findings could have relevance beyond COVID-19, said Dr. Elif, who notes the research could open latest avenues of research for the treatment of other infectious and inflammatory diseases.