A rash of cases of a rare “black fungus” infection affecting thousands of critically ill Covid patients in India caused alarm last month. Now scientists are warning that other dangerous or even deadly fungal infections have spawned in critically ill coronavirus patients globally, including in the UK.
Fungi are ubiquitous – in soil, water, air, faeces and human skin. Usually, people’s elaborate, adaptive immune systems are enough of a repellent but when that shield is weakened by disease, congenital conditions or age, they are far more vulnerable to microscopic assailants.
When Covid-19 emerged, doctors found that the best tools in their arsenal to fight the virus were steroids, which happen to be immunosuppressants. Wary of secondary bacterial infections in intensive care units, doctors often gave coronavirus patients broad-spectrum antibiotics as a precaution.
But the combination of lungs battered by Covid, impaired immune systems, and both good and bad bacteria wiped out by antibiotics left critically ill patients exposed to moulds and spores.
“It’s an unfortunate perfect storm for these organisms, and we’re seeing it,” said Dr Tom Chiller, the chief of the Mycotic Diseases Branch at the US-based Centers for Disease Control and Prevention (CDC).
Even before the pandemic, rates of the rare and lethal “black fungus” mucormycosis infection in India were estimated to be about 70 times higher than in the rest of the world. With Covid, a fresh epidemic germinated, driven in part by liberal steroid use in hospitals and a high proportion of susceptible patients with uncontrolled diabetes.
Scientists now say concerning reports of other fungal infections, caused by pathogens including Aspergillus and Candida auris, have emerged in hospitalised Covid patients. In particular, the common fungal infection aspergillosis, often seen in combination with the flu, has been observed in critically ill Covid patients globally, from the US to the UK, France, Pakistan and India.
A recent meta-review of 19 observational hospitalised Covid patient studies from various countries showed the overall incidence of Covid-associated pulmonary aspergillosis was 13.5% from 1,421 patients, with a range of 2.5% to 35%. Despite the widespread use of antifungals, nearly half of those infected died.
“Essentially, the more damage there is in the lung from a virus, the more likely you are to get a fungal infection,” said Dr Darius Armstrong-James, a clinical senior lecturer in respiratory fungal diseases at Imperial College London. “And the problem with fungal infections is that they’re much more lethal than bacterial infections. They’re difficult to treat, difficult to diagnose and cause a lot more mortality.”
Armstrong-James, who also leads the fungal diseases unit at the Royal Brompton hospital, estimated that roughly 10% to 15% of critically ill Covid patients have caught aspergillosis in hospitals in the UK, based on his own work as a clinician.
Diagnosing aspergillosis is difficult in Covid cases because it involves sampling fluid from the lungs, which is routine in Europe and North America but not elsewhere, said David Denning, a professor of infectious diseases and global health at the University of Manchester.
“Some people won’t want to take that fluid, because there’s a risk of the [virus that causes] Covid … getting into the air in the intensive care unit and infecting the people doing the procedure. There’s a reluctance to make a diagnosis.”
“Mucormycosis is very visible … the patients look terrible, they’ve got these black areas on their face, they’re losing their eye … it needs a big-time surgery, it looks dreadful,” he said. “A patient with aspergillosis is just sick on a ventilator, and they’ve already got a bad lung disease with Covid. And if they then die, then it’s all attributed to Covid.”
Given these hurdles, undercounting of aspergillosis cases was “extremely likely”, he added. He said the trend of these infections in hospitalised Covid patients was grave enough to justify administering antifungal treatments prophylactically, as doctors do with antibiotics. Research to assess the feasibility of that approach is ongoing.
According to Chiller, roughly half of those infected with mucormycosis tend to die – and aspergillosis can be just as deadly, especially in intensive care patients with Covid. “The important thing is to think fungus,” he said. “If you don’t think it, you’re not going to diagnose it, you’re not going to treat it, you’re not going to save lives.”