Certain gut-dwelling fungi flourish in severe cases of COVID-19, amplifying the excessive inflammation that drives this disease while also causing long-lasting changes in the immune system, according to a new study.

Utilising patient samples and preclinical models, researchers at Weill Cornell Medicine and NewYork-Presbyterian in the US determined that the growth of fungi in the intestinal tract, particularly strains of Candida albicans yeast, trigger an upsurge in immune cells whose actions can exacerbate lung damage. 

Their findings, published in the journal Nature Immunology, also elucidate that patients retain a heightened immune response and immune memory against these fungi for up to a year after the resolution of SARS-CoV-2 infection.

The research reveals a new dimension of the complex pathology unleashed by severe COVID-19, said Dr Iliyan Iliev, immunologist and Associate Professor in the Department of Medicine at Weill.

"Severe and long COVID-19 were not thought to involve fungal blooms in the intestines that, in addition to the virus, can impact a patient's immunity," he said.

The team first made the connection when analysis of blood samples from patients diagnosed with severe COVID-19 unveiled the presence of antibodies tuned to attack fungi common to the gut. The researchers then found that populations of yeast, and one species in particular, Candida albicans, increased in the intestines of the patients during the course of severe COVID.

When they looked at the patient's immune systems, the researchers found a parallel increase in immune cells called neutrophils. In severe COVID, 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 experimental model-bearing fungi from patients with severe COVID-19 produced more neutrophils in their blood and lungs, and had signs of heightened inflammation when infected with SARS-CoV-2. However, giving them an antifungal drug reduced these effects.

From within patients' blood samples, researchers also uncovered evidence of persistent changes to the immune system they believe are related to a condition known as long COVID, in which symptoms linger, or new ones develop after an infection has cleared.

When the team examined patients' blood up to a year afterwards, they found it still contained anti-fungal antibodies. In addition, when they looked at the stem cells that give rise to neutrophils, the researchers found that these progenitors are primed to respond to fungi. 

They found that an immune protein called IL-6 that these fungi induce, appears to bolster both the neutrophils and the antibodies.

Further experiments showed that blocking IL-6 in the patients or in the experimental model dampened this immunological memory, causing the presence of neutrophils and antibodies to wane.

While these results do not have immediate implications for treating severe or long COVID-19, they suggest new opportunities to tailor therapy, according to Dr. Iliev.