INTERVIEW BY ANNALIES WINNY
As India battles a devastating wave of COVID-19 cases, another crisis is waiting in the wings that could far outlast the pandemic—in the form of a chronic fungal disease that kills slowly and is extraordinarily difficult to treat.
Preying on recovering coronavirus patients, India has seen some 30,000 cases of mucormycosis, better known as “black fungus,” in recent months.
The illnesses caused by the fungus Mucor—mucormycosis—are well known, with an overall mortality rate of ~54%.
But the scale of India’s outbreak is rare. Mucor, which can lodge deep into the sinuses or lungs, has already killed hundreds in India, and forced others to have an eye excised to remove the fungus.
Why is it sweeping India at the same time as COVID? Arturo Casadevall, a leading expert on fungi and Bloomberg Distinguished Professor in Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health, explains why the liberal use of steroids in treating COVID-19 is a key factor, and why India’s Mucor crisis is a warning sign for the rise of fungal infections across the globe.
What exactly is Mucor, or “black fungus”?
We are all breathing in fungal spores constantly—for example when we walk by construction sites, or compost piles—but healthy people clear them easily without experiencing illness.
Mucor is a particularly nasty fungus—and for those who can’t clear it, it tends to kill slowly.
If it lands in the sinuses or brain, it can cause facial swelling, nasal congestion, and headache. In the lungs: fever, cough, and shortness of breath.
What’s with the name?
The name “black fungus” comes not from the fungus itself, but from black lesions in patients sickened with mucormycosis.
The fungus itself is not particularly black, even though it makes melanin, a pigment that is a secret weapon to almost all fungi, including Mucor.
When Mucor lands in the lung, it begins to grow and kill tissue as it expands into a fungal mass which kills tissue, which causes scarring that makes the tissue appear black.
The fungus—in fact most fungi—uses this black melanin pigment as “armor” which enables it to survive the body’s immune defenses and evade drugs. This is quite different from how humans use melanin, for protection against sunlight.
Why is this particular fungus so dangerous to COVID patients?
Mucor preys on those with weakened immune systems—and COVID patients have two hits against them when it comes to Mucor: One, they have damaged lungs. Scar tissue from COVID-related lung damage makes it more difficult for the immune system to clear the spores—scar tissue does not respond very well to infection. Two, to treat inflammation, many of these patients have been put on steroids, which are immunosuppressants.
What’s the big picture lesson for treatments here?
I think one of the problems that this crisis has exposed is overuse of steroids—it’s an epidemic, really. Doctors are putting many patients on steroids, yet the data [show] that steroids are only beneficial in COVID-19 patients who are very severely ill.
COVID is an infectious disease; steroids are an immunosuppressant. If you give them too early, this is going to work against you. So I think physicians need to be more careful with steroid use.
When a coronavirus patient is not improving as expected, doctors need to [suspect] fungal disease. You’re always better [off] treating an amount of fungi the size of a dime than treating something the size of an apple.
Why is India being so hard-hit by this fungus?
I think the most likely explanation right now is that it reflects local climate conditions and large numbers of COVID-19 patients who are susceptible.
What I would like to know is, what is in the air in India, and whether this reflects local farming conditions and how vegetation is disposed of. Compost piles, for example, contain enormous amounts of fungal spores. Anywhere you have decaying vegetation [and] rotting wood are places you tend to get a lot of fungi. It could be as simple as vegetation rots faster in the tropics, resulting in more spores.
In weaker health systems, poorly filtered air in hospitals can also encourage spores to spread.
So fungal infections aren’t just spreading in India?
While India is getting a lot of Mucor, other parts of the world are seeing a rise in other fungi. The Netherlands and United States are seeing a rise in another fungus—Aspergillus—among COVID-19 patients.
The common theme is, with the combination of damaged lungs and steroids, you’re going to get fungal disease. Depending where you are, you’re going to end up with different ones.
Looking beyond India, the bigger story is that amid this pandemic, fungal infections are a major calamity because they are so hard to diagnose and treat.
Why is this infection so hard to treat?
The only thing that can be used to treat this is a drug called amphotericin B—which doesn’t work very well and has to be given for months intravenously. In India, there are shortages of it because of the COVID crisis.
Because the antifungal drugs don’t work well with Mucor, often the only option is to remove a piece of the lung or an eye, surgically, depending on where the fungus took hold.
How is mucormycosis diagnosed?
There is not a simple blood test. Sadly, the way it would manifest is that people don’t get better as expected.
Mucor [mycosis] only gets diagnosed when the symptoms get sufficiently bad, and once Mucor is causing symptoms, the immune system cannot clear it.
First the lung will show a lesion. At first, you don’t know if this lesion is just scar tissue from COVID, whether it’s a bacterial pneumonia, or whether it’s a fungal pneumonia.
One of the only ways to make a diagnosis is very invasive—using a scope to take a piece of lung tissue and look at it under the microscope. Then you see the fungus growing into the tissue.
Given the extremely limited ability to diagnose, the cases seen so far are probably the tip of the iceberg, sadly.
India is going to have a big problem going forward with patients who survived COVID but now have chronic mucor [mycosis]—and that will kill them down the line.
It’s just nightmarish.
Annalies Winny is associate editor of Global Health NOW and an editor of the Expert Insights newsletter from the Johns Hopkins Bloomberg School of Public Health.