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Intestinal fungi may worsen lung inflammation in severe COVID-19 for up to 1 year - University of Minnesota Twin Cities

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Stephanie Rossow / CDC

In severely ill COVID-19 patients, some kinds of fungi can thrive in the intestines, exacerbating the virus's characteristic inflammation and leading to an outsized immune response against the fungi for up to 1 year after infection, suggests a study published yesterday in Nature Immunology.

Weill Cornell Medicine and New York Presbyterian researchers analyzed blood samples from patients with severe COVID-19, finding immunoglobulin G (IgG) antibodies against fungi commonly found in the gut and an increase in neutrophil immune cells in the lungs.

They then used mouse models to confirm that fungi in the gut, especially strains of Candida albicans yeast, provoked the production of more neutrophils in the blood and lungs. The mice also had signs of inflammation when infected with SARS-CoV-2.

No immediate implications for treatment

Patient blood samples showed signs of persistent immune-system changes believed to be related to long COVID. At 1 year postinfection, the blood still contained antifungal antibodies, and stem cells that give rise to neutrophils were primed to attack fungi.

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

The immune protein interleukin-6, induced by fungi, seemed to increase levels of both neutrophils in the lungs and fungal antibodies. The use of IL-6 blockers or antifungal drugs in patients or mice, however, reduced levels of neutrophils and fungal antibodies. Patients treated with the anti-inflammatory drug tocilizumab saw sustained reductions in IgG antibodies against both C albicans and neutrophil progenitors.

"Severe and long COVID-19 were not thought to involve fungal blooms in the intestines that, in addition to the virus, can impact patient’s immunity," senior author Iliyan Iliev, PhD, of Weill Cornell Medicine, said in a college news release.

The authors said the findings don't change the guidelines for treating severe or long COVID, but they may someday lead to tailored treatment, such as the use of antifungal antibodies to identify patients eligible for a therapy targeting the fungi or the immunologic changes they trigger. The antifungal antibodies may also be a marker of increased risk of long COVID or other infectious inflammatory conditions.

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Intestinal fungi may worsen lung inflammation in severe COVID-19 for up to 1 year - University of Minnesota Twin Cities
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