Covid-19 has killed millions around the world, but for some who are lucky enough to survive the infection, the nightmare is not over: adding insult to injury are deadly fungal infections that follow in the wake of the virus. Making matters worse, inequities that long predated the pandemic have left some countries without the capacity to combat these serious infections.
In India, a fungal infection called mucormycosis has emerged in patients with Covid-19. This infection is caused by a group of fungi that are everywhere on the planet. In fact, all of us are probably inhaling spores of these fungi every day, but these are rapidly controlled by our immune systems. Rarely, our defences are breached, and the fungus takes hold, with devastating consequences. After establishing itself in the nose and sinuses, it begins to invade the tissue of the face, the jaw, the eyes and brain, blocking blood flow and causing tissue death. It is the black discoloration of dead tissue that conferred upon this mould its fearsome moniker in the Indian media: “the black fungus”.
Although the fungi are ubiquitous, mucormycosis is usually rare, and most specialists around the world will see fewer than a dozen cases in their entire careers. Even before the pandemic, rates of mucormycosis in India were estimated to be about 70 times higher than in the rest of the world. Even so, the tsunami of cases occurring in the wake of Covid-19 is of an unimaginable scale. More than 11,700 people were reported by a government minister to be receiving care for mucormycosis on 25 May. Two states, Maharashtra and Gujarat, have confirmed more than 5,500 cases. Whereas a large referral hospital in London might see three or four cases a year, some Indian hospitals are caring for more than 500 patients with mucormycosis right now.
Mucormycosis cases in Covid-19 patients have also been linked to poorly controlled diabetes and therapeutic steroids, a triad of risk factors some have dubbed “the unholy trinity”. Although steroids can be lifesaving in Covid-19 patients needing supplemental oxygen, they are a double-edged sword: they weaken the immune system that normally keeps fungi we inhale at bay. Undisciplined prescribing is likely to be playing a major role in driving the epidemic: one study at 16 Indian hospitals found that nearly two in three steroid prescriptions for Covid-19 patients were inappropriate (they were either used in patients who weren’t sick enough to warrant them, or the dose was too high). Lack of access to oxygen may have resulted in doctors overcompensating by prescribing higher-than-recommended doses.
Additionally, rates of diabetes have been increasing in India, and high blood sugars further weaken the immune system and increase the growth of fungi in the body. High blood sugars are also a well-known side-effect of steroids, particularly in diabetic or prediabetic patients, and overstretched healthcare workers have been unable to adequately monitor blood sugar levels of Covid-19 patients on crowded wards. The confluence of these risk factors, plus higher-than-average background rates of mucormycosis, high numbers of spores in both indoor and outdoor environments, and the lack of hospital infection-control resources (like efficient air particle filters in ICU rooms, standard in resource-rich settings to filter out airborne spores) have allowed the fungus to run amok.
Mucormycosis is rapidly fatal without prompt diagnosis, administration of antifungal medicines and – most importantly – emergency surgery to cut out the dead and infected tissue. This lifesaving surgery can be extremely disfiguring and lead to irreversible loss of one or both eyes. Even with surgery, half of those infected won’t survive. Most cases develop in the second or third week following a Covid-19 diagnosis, when many patients are no longer in hospital. The partial closure of outpatient clinics and the shortage of specialised doctors have meant that affected patients present to hospital later in the disease, when the odds of survival are lower.
The mucormycosis epidemic has been accompanied by a rush for antifungal treatments that have left India’s medicine cabinet empty. The nation’s supply of amphotericin B, the best antifungal to treat the infection, is nearly depleted and it is difficult to procure. The government has pledged to increase importation and ramp up domestic production of the drug, but this will take several weeks to months. There are only two other medications that can be used for this infection: posaconazole, now generic in India; and isavuconazole, patented and expensive. Both are in critically scarce supply.
Unsurprisingly, the epidemic has led to fear and rumours. Some have suggested that oxygen supplies may be contaminated, but the fungus cannot tolerate high oxygen concentrations, and there has not been any empirical evidence to support this assertion. Mucormycosis is not contagious, and infected individuals do not need to be isolated.
India’s mucormycosis epidemic is a reminder of two cruel realities that Covid-19 has laid bare: 1) our universal vulnerability to the capricious whims of nature; and 2) the stark inequities in the distribution of resources to weather the storm. We cannot solve global inequities overnight, but there are some concrete steps that governments around the world can take to help India through this horror. Drug manufacturers must prioritise getting antifungal therapies into India as quickly as possible, and governments in wealthy nations need to hold these corporations to task. In the longer term, investment must be increased for researching fungal diseases, especially those that disproportionately affect the world’s poor. Ultimately, the best way to end this nightmare is to end the pandemic as soon as possible, and this is best achieved through vaccination; this fungal epidemic makes the equitable redistribution of global vaccine caches that is needed to minimise human suffering from this virus even more urgent.
Ilan Schwartz is an infectious diseases doctor at the University of Alberta, Canada. Prof Arunaloke Chakrabarti is the president of the International Society for Human and Animal Mycology, and a global expert on mucormycosis.