In addition to aspergillosis, a disease caused by fungi of the genus Aspergillus, co-infection with COVID-19 is caused by two other groups. Mushrooms of the order Mucorales are the cause of mucormycosis, which occurs mainly in India and Pakistan, while yeasts of the genus Candida cause candidiasis and are present throughout the world.
Martin Hoenigl, first author of the study, told Agncia FAPESP: “Patients with this co-infection were twice as likely to die as patients with SARS-CoV-2 alone. Hoenigl is a professor at the University of California San Diego in La Jolla (USA) and at the University of Graz (Austria).
Antifungal Infections & COVID
According to the article, aspergillosis can stay in the upper respiratory tract for several days and can be controlled with antifungal medications. However, once it has entered the blood vessels in the lungs, the mortality rate exceeds 80% even with systemic antifungal therapy.
Candidiasis occurs almost exclusively in patients in the intensive care unit and no more frequently in patients with COVID-19 than in patients hospitalized for other reasons. However, Candida auris, an emerging fungus, is a concern because it can invade the skin. In addition, it appears to be the only fungus that is transmitted from person to person. This species is resistant to all known antifungal drugs and is present in many environments, can easily infect patients using mechanical ventilators or by catheters and assistive devices. Other invasive lives are available in the hospital (see more at: agencia.fapesp.br/36111).
COVID-19-associated mucosal infections (CAM) are a serious problem, especially in India, where the number of cases has doubled during the pandemic. News of this fungal disease gained international attention in 2021 when more than 47,500 cases were reported in India between May and August alone. Classified by the Indian government as a disease epidemic, it is erroneously called “black fungus” because of the color of the tissues necrotic by the disease. Black fungus is in fact part of a different group that is relatively distant from the Mucorales and is not pathogenic to humans.
In patients with COVID-19, mucormycosis most commonly appears in the eye and nose area, and may reach the brain. The mortality rate is 14% in these cases, in which the two diseases co-occur. Since mucormycosis causes necrosis, it may require surgery and ultimately disfigure the patient. Patients who survive it may lose facial features and suffer problems for the rest of their lives. If the lungs are affected, or the fungus spreads throughout the body, the mortality rate is up to 80%.
“The prevalence of this fungal disease in India is 0.27% among hospitalized patients with COVID-19, although it frequently occurs in people outside the hospital, such as those receiving treatment. at home with very high doses of systemic steroids, which are readily available to most Indians,” says Hoenigl.
The use of steroids and other drugs that reduce the activity of the immune system is one of the causes of the global increase in fungal infections. While this strategy has been successful during the pandemic and the benefits outweigh the risks, the researchers caution that it’s important to avoid overuse of immunosuppressants.
As an alternative, several high-risk centers for aspergillosis have successfully implemented anti-fungal prophylaxis during the pandemic using pre-infection drugs with these agents. However, because the fungus is generally resistant to most currently available drugs and there are not enough clinical studies to evaluate the strategy, it is not currently recommended.
“Immunosuppressive drugs are a major advance in medicine. They prevent many deaths from cancer and autoimmune diseases, as well as play an important role in organ transplantation. However, one A side effect of their use is a significantly increased incidence of fungal infections,” says Goldman. “With the exception of some heat-tolerant species, such as A. fumigatus, fungi are generally not able to withstand the body heat of animals. mammals and are easily resisted by our innate immunity. But when our immune systems are too weak to fight off highly inflammatory diseases like COVID-19 they take the opportunity to attack us. ”
In addition, many fungi are adapting to higher temperatures as the global climate warms, and this also makes humans more vulnerable. Therefore, experts agree that new antifungal drugs are needed. There are currently only four antifungals, for example, compared to dozens of bacteria (antibiotics).
Another problem is the difficulty of diagnosing fungal infections. Diagnostic tests are too expensive for most people in low- and middle-income countries, and test results can take too long to get appropriate treatment prescribed.
For example, a 100% sure diagnosis of aspergillosis would require bronchoscopy, a test considered high risk during the COVID-19 pandemic and therefore should be avoided as much as possible. The amount of fluid ejected from the patient during the procedure is more than enough to transmit SARS-CoV-2 to the medical team. Therefore, cases of aspergillosis can be underestimated.
“The good news is that several new antifungal drugs have been developed and are currently in phase 2 and 3 clinical trials,” says Hoenigl.
However, the researchers fear these novel drugs won’t reach everyone who needs them. Advanced treatments may remain limited to rich countries, as inequalities in their availability are likely to continue.
“In the context of global warming with few drugs available and diseases that weaken immunity and cause epidemics and pandemics, the likelihood of outbreaks of fungal infections is very high. We need more. more tools to control them and more scientists to study different fungi and their mechanisms of action,” said Goldman.