Over Christmas break in 2015, Johanna Rhodes received a panicked email from a doctor working at the Royal Brompton Hospital, the largest heart and lung center in the United Kingdom. A horrid yeast was invading the skin of patients, spreading through the intensive care unit even though the hospital maintained extensive protocols for infection control.
“The doctor asked me to take a look … I thought, how bad can it be?” recalls Rhodes, an infectious disease expert at Imperial College London who studies antifungal resistance. Rhodes stepped in to help one of the world’s top cardiology hospitals identify the pathogen and clear it from the premises. The germ was Candida auris, little known at the time. What she saw stunned her: “You think COVID-19 is bad until you see Candida auris.”
Candida auris is a superbug, a pathogen that can evade drugs made to kill it—and early signs suggest the COVID-19 pandemic may be propelling infections of the highly dangerous yeast. That’s because C. auris is particularly prominent in hospital settings, which have been flooded with people this year due to the coronavirus.
The superbug sticks stubbornly to surfaces such as sheets, bed railings, doors, and medical devices—making it easier to colonize skin and pass from one person to another. Moreover patients who have tubes that go into their body, such as catheters or ones for breathing or feeding, are at the highest risk for C. auris infections, and these invasive procedures have become more common because of the respiratory failure associated with COVID-19.
“Unfortunately, there have been places where we’ve seen a resurgence of C. auris,” says Tom Chiller, head of the mycotic diseases branch at the U.S. Centers for Disease Control and Prevention. “We’ve also seen it get into some of the acute care hospitals and also into some COVID-19 units … the concern there is that once it sets up shop in a place, it’s hard to get rid of.”
Prior to its emergence in 2009, fungi in the genus Candida were best known for causing benign cases of thrush, a white overgrowth on the tongue or genitals. A few thousand C. auris infections have since spread to at least 40 countries where they’ve been tied to deaths in 30 to 60 percent of cases. By comparison, the coronavirus kills about one percent of the infected but has afflicted a larger number of people in a short timespan.
The worry is that if C. auris becomes more common in hospitals or the general public, it could bolster the growing crisis of superbugs, which already infect millions worldwide. Last year, the CDC classified C. auris as one of the biggest drug resistance threats in America. Now, though it’s too early to confirm a direct knock-on effect, the U.S. has recorded 1,272 confirmed cases of C. auris in 2020, a 400 percent increase over the total recorded during all of 2018, the most recent year with available data.
The real number is likely to be much higher, though, as the COVID-19 pandemic has halted much of the disease surveillance for C. auris at hospitals and because the germ can often colonize a person’s skin without generating symptoms.
“How will we treat it?”
In 2011, Anuradha Chowdhary was working in her laboratory in New Delhi, when she received an unexpected pile of blood samples from two hospitals in the sprawling city. Mysterious fungal infections had sprouted in intensive care units and neonatal wards so Chowdhary, a professor of medical mycology at Vallabhbhai Patel Chest Institute at the University of Delhi, was recruited to identify the germ through genetic screening and to recommend the best drug for treatment. The results left her dumbfounded.
The yeast samples collected from the patients—known as isolates—weren’t in the identification system that microbiology labs use to track fungal infections, she says. “It was Candida auris. I had to ask: ‘What is C. auris?’”
The superbug had first been identified two years earlier in a patient's ear (“auris” is Latin for ear), but Chowdhary hadn’t seen it before. The biggest surprise was that all the specimens were resistant to fluconazole—the first-line drug for treating a variety of fungal and yeast infections. Since she and her group published their study on the New Delhi outbreak in 2013, researchers have learned that C. auris is nearly always resistant to this medication and the chemical relatives in its family—known as azoles. Some variants are also impervious to the other two main classes of antifungal drugs.
That’s why Chowdhary has now pivoted to address critically ill COVID-19 patients who were admitted to an ICU in Delhi and acquired candidemia, a Candida fungal infection in the bloodstream. In a small study published August 27, her team found 10 of 15 such patients had drug-resistant C. auris—which was likely acquired inside the hospital.
All the specimens could flout fluconazole, but four of the C. auris isolates were also resistant to amphotericin B, a second-line antifungal drug. Resistance to two classes of drugs is particularly concerning because India has limited access to the third option for antifungal treatment: echinocandins. Six of the patients died.
“Our worry right now is that we’re seeing published cases of patients with COVID-19 and other fungal infections, with people getting really sick and dying,” says Rhodes, as she and other clinicians in the U.K. face the coronavirus’s autumn surge. “We expect to see the same with C. auris.”
Both she and Chowdhary emphasize the importance of testing and contact tracing—key interventions in the control of COVID-19 that are also critical in the fight against the spread of C. auris. They’re pushing for patients to be routinely screened for the superbug, which involves collecting a skin swab, blood, or urine to test for the yeast’s DNA. After a patient tests positive for C. auris, a medical procedure known as susceptibility testing is done to determine if any of the three classes of antifungal drugs can alleviate the infection.
These tactics can help track the deaths caused by the superbug, a process that is often complicated because the germ tends to be acquired in hospitals among people who are already sick with something else.
“If we don’t identify it, then we don’t know if a patient is dying of COVID-19 or another infection,” Chowdhary says, but “if it’s resistant to drugs, how will we treat it?”
The pandemic duel
In 2019, the World Health Organization listed antimicrobial resistance as one of the top ten threats to global health. The agency’s fear is that humanity is returning to a time when easily treatable infections—such as tuberculosis and gonorrhoea—can no longer be kept under control.
The global overuse of antimicrobial drugs on farm animals and in human medicine has been pegged as a cause for the emergence of superbugs. But looking ahead, Ramanan Laxminarayan, founder and director of the Center for Disease Dynamics, Economics & Policy in Washington, D.C., says he and other researchers are concerned about the role climate change will play in the spread of fungal infections.
A research review published last year in mBio, a journal of the American Society of Microbiology, suggests that C. auris “may be the first example of a new fungal disease emerging from climate change.” When humans suffer from infections, we tend to develop fever as a defense. The hot temperatures help kill off the germs, in a concept known as the mammalian thermal restriction zone. The report argues that as fungal species like C. auris adapt to higher environmental temperatures due to global warming, they may breach this thermal defense. That means in the future we may not only see existing fungal infections spread, but new ones taking hold in humans.
“Fungal resistance could be as dangerous as antibiotic resistance,” Laxminarayan says, hinting at superbug bacteria such as Clostridioides difficile or multidrug-resistant tuberculosis. Those potent bacteria account for 99 percent of the 2.8 million superbug infections reported every year in the U.S., which leads to approximately 35,000 deaths.
India has long been viewed as a hotbed of drug-resistance, and now the nation has become Asia’s epicenter for COVID-19. Back in New Delhi, half of Anuradha Chowdhary’s laboratory staff have recently tested positive for COVID-19. Two have died. Despite the personal hardship, she is grateful that people are waking up to the danger C. auris poses.
“Everyone initially thought this was an India-centric problem—that it wasn’t their problem,” she says. “I was struggling and working alone but I’m glad now that the world is working on it. Fungal infections shouldn’t be neglected.”