'Advanced medicines still can't treat these': Deadly fungal infections a concern post-COVID-19, influenza

Not quite 'The Last of Us' but deadly all the same Fungi can cause deadly infections, especially in people with weakened immune systems such as those recovering from COVID and influenza.

While fungi are not about to start turning the human race into zombies, like in the HBO blockbuster series The Last of Us, the World Health Organization (WHO) says invasive fungal infections are an increasing threat to human health.

Aspergillosis is one fungal infection common in our environment but, in some circumstances, it can turn deadly. In an average day, most of us will inhale hundreds to thousands of Aspergillus spores with no adverse effects, but for people with weakened immune systems it can cause deadly infections. That includes people undergoing cancer treatments, or bone marrow transplants, but it is now recognized that some viral infections, like influenza (flu) and SARS-CoV-2 (COVID-19) increase the risk of deadly fungal infection even in otherwise healthy people.

"When these kinds of things happen in the ICU, it can be devastating because even advanced medicines still can't treat these infections," said Dr. Bryan Yipp, an intensive care physician and researcher at the University of Calgary.

"Once many of these infections really get ingrained and take over, clearing them with medications alone, antifungal or anti microbials, can be very difficult."

Dr.Yipp began studying Aspergillus — a type of fungus that is a common mould — and its connection to viral infections in 2019, following three deaths in intensive care units of patients initially admitted for influenza, but who subsequently died of the fungal infection.

"It was very much a surprise when people first started identifying the fungus in the lung.  There was a lot of discussion around the table of ICU doctors, infectious disease doctors, asking 'Was Aspergillosis really the cause of death, or was this just a secondary finding?'" said Yipp. "The pathologists who looked at the samples and the autopsies, were convinced that it was Aspergillosis that was the main problem."

Working in Yipp's lab, lead researcher Nicole Sarden, a PhD candidate, isolated the mechanism by which the immune system starts failing to prevent fungal infections.

"In healthy humans. specific immune cells, called B cells, produce molecules (antibodies) that basically tag invaders so that other cells in the immune system, called neutrophils, can recognize them, eat them, and clear the infection," said Sarden

"But when you have infections with viruses, such as influenza, or if you get COVID, these molecules are no longer present, which means that the immune systems that are trying to eat, and clear the fungi cannot do it because they cannot see it."

Working with both mice and human blood and tissue samples, the researchers discovered that following a viral infection, neutrophils could identify a fungal infection and surround it but did nothing to destroy it.

"The virus kills the B cells, no messenger molecules exist, so the neutrophils that would normally attack, the fungus, are blinded. They sit there and don't know what to do," said Sarden.

The research team also discovered that reintroducing Aspergillosis reactive antibodies can protect infected mice, leading to hopes a similar treatment will be available in the near future for humans with Aspergillosis infections.

While Yipp and Sarden focused on Aspergillus, it is not the only fungus that can cause serious, or fatal infections. It is estimated fungal infections kill an estimated 1.5 million people worldwide every year. Most of those are due to four different fungi; Cryptococcus, Candida, Aspergillus, and Pneumocystis.  Since the advent of COVID, a previously rare infection of the fungus Mucormycosis has been increasing rapidly in India. It affects the sinuses, brains and lungs of its victims. The rise in Mucormycosis has also been seen in patients who are recovering or have recently recovered from COVID.

Yipp is hopeful the research being conducted at Calgary's Cumming School of Medicine could lead to treatments for these infections as well.

"We have some hunches that that could be a similar mechanism to what we see here with what we have found." said Yipp. "So we think that this could be applied to multiple different types of fungi around the world."

The research team, led by Sarden, published their findings in the journal Science Translational Medicine.