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Fungal infection increases mortality in COVID patients

In addition to aspergillosis, a disease caused by fungi of the genus Aspergillus, co-infections with COVID-19 are caused by two other groups. Fungi of the order Mucorales are responsible for mucormycosis, which occurs mainly in India and Pakistan, while yeasts of the genus Candida cause candidiasis and are practically present worldwide.

“Patients with this co-infection are twice as likely to die than patients infected with SARS-CoV-2 alone,” study first author Martin Honigal told Agnia FAPESP. Honigal is a professor at the University of California San Diego in La Jolla (USA) and at the University of Graz (Austria).

Antifungal Infections and COVID

According to the article, aspergillosis can be confined to the upper airway for several days and can be contained with antifungals. Once it invades the blood vessels in the lungs, however, the mortality rate exceeds 80% even when systemic antifungal therapy is administered.

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Candidiasis occurs almost exclusively in patients in intensive care units and does not occur more often in COVID-19 patients than in those hospitalized for other reasons. However, Candida auris, an emerging fungus, is a concern because it can colonize the skin. Furthermore, it appears to be the only fungus to be transmitted between people. The species is resistant to all known antifungals and, being present in a wide range of environments, can readily infect patients on mechanical ventilators or with catheters and other invasive life support equipment present in hospitals (more here: agencia .fapesp.br/36111) .

COVID-19-associated mucormycosis (CAM) is a serious problem, especially in India, where the number of cases has doubled during the pandemic. News of this mycosis attracted international attention in 2021 when over 47,500 cases were notified in India in the May-August period alone. Classified as an epidemic by the Indian government at the time, it was mistakenly called “black fungus” because the disease caused tissue discoloration. The true black fungus is part of a separate group that is relatively distant from the Mucorales and does not cause disease in humans.

In COVID-19 patients, mucormycosis often occurs in the eyes and nose area, and can reach the brain. The mortality rate in these cases is 14%, with both diseases occurring together. Since mucormycosis causes necrosis, it may require surgery and may disfigure the patient. Patients who survive this can lose parts of their face and suffer from problems for the rest of their lives. If the lungs are affected, or the fungus spreads throughout the organism, the mortality rate reaches 80%.

“The prevalence of this mycosis in India was 0.27% in patients hospitalized with COVID-19, although it often occurs in people outside hospitals, such as those treated at home with very high doses of systemic steroids, Which is easily obtained by most of the Indians,” Honigal said.

The use of steroids and other drugs that reduce the activity of the immune system is one of the reasons for the global increase in fungal infections. While the strategy was successful during the pandemic and the benefits outweighed the risks, the researchers caution that it is important to avoid abusive administration of immunosuppressant drugs.

As an alternative, some centers at high risk for aspergillosis successfully implemented antifungal prophylaxis during epidemics by administering drugs prior to infection by these agents. However, because fungicides are often resistant to most available drugs and there are insufficient clinical studies to evaluate the strategy, it is not currently recommended.

“Immunosuppressants 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, a side effect of their use is a significant increase in the incidence of fungal infections.” Told. “Except for some heat-tolerant species, such as A. fumigatus, fungi generally cannot tolerate mammalian body temperature and readily compete with our innate immunity. Very vulnerable to something like COVID-19, they take this opportunity to attack us.”

novel drugs

In addition, many fungi are adapting to higher temperatures as the global climate warms, and it also makes humans more vulnerable. Consequently, there is an urgent need for novel antifungal drugs, experts agree. For example, there are currently only four classes of antifungals, compared to dozens of classes of antibacterials (antibiotics).

Another problem is the difficulty in diagnosing fungal infections. Diagnostic tests are too expensive for most people in low- and middle-income countries, and it can take a long time before test results are available for the right treatment to be prescribed.

For example, a 100% definitive diagnosis of aspergillosis requires bronchoscopy, a type of examination considered highly risky during the COVID-19 pandemic and therefore avoided as much as possible. The amount of fluid removed from the patient during the procedure is more than enough to transmit SARS-CoV-2 to the medical team. Aspergillosis cases are probably underestimated as a result.

“The good news is that several novel classes of antifungals have been developed and are currently in phase 2 and 3 clinical trials,” Honigl said.

However, researchers fear that these new drugs may not reach everyone who needs them. State-of-the-art treatments may remain confined to wealthy countries, as their availability inequalities are likely to continue.

“With few available drugs against the background of global warming, and diseases that weaken immunity while causing epidemics and epidemics, there is a high potential for outbreaks of fungal infections. We need more scientists to control them so that to study different fungi and their mechanisms of action,” Goldman said.

Source: Eurekalert

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