Every day we inhale thousands of potentially pathogenic fungal spores, but our immune system simply eliminates them. However, in people whose immunity is compromised – transplant recipients, patients undergoing cancer treatment or hospitalized in Intensive Care Units (ICU) −, this interaction between pathogens and hosts can be quite different. (Read Polio State of Emergency Declared in New York)
An example of this is the cases of fungal infections that emerged during the covid-19 pandemic and enhanced the action of SARS-CoV-2 on the planet. Among patients affected by the severe form of covid-19 and simultaneously infected with the fungus Aspergillus fumigatus, mortality reached 80%. (Lea Minsalud requested to suspend the application of two batches of Moderna)
An international group of scientists conducted a joint study of the burden of these co-infections (coronavirus and fungi) in the world during the health crisis. And that work, published in the magazine Nature Microbiology issues some warnings regarding this and future pandemics.
“The central issue with fungi is that they are a highly neglected public health problem with few treatment options. There are now more deaths from fungal diseases than from malaria and tuberculosis combined, for example. That is why it is not surprising that fungal diseases have taken advantage of so many people hospitalized due to covid-19,” says Gustavo Henrique Goldman, professor at the Ribeirão Preto School of Pharmaceutical Sciences, University of São Paulo (FCFRP-USP). , in Brazil, and one of the coordinators of the study, which had the support of FAPESP.
Apart from aspergillosis, a disease caused by fungi of the genus Aspergillus, other groups cause simultaneous infections with covid-19. The Mucorales are responsible for mucormycosis, with records mainly in India and Pakistan. The yeasts of the genus Candida, in turn, cause candidiasis and are present practically everywhere on the planet.
“Aspergillosis associated with covid-19 [ una condición denominada CAPA, por sus siglas en inglés] It affects an average of 10% of patients with acute respiratory failure admitted to the ICU. Carriers of this coinfection are twice as likely to have fatal outcomes than individuals infected only with SARS-CoV-2″, Martin Hönigl, a professor at the University of California San Diego, in La Jolla, United States, tells Agência FAPESP. , and the University of Graz, in Austria, first author of the study.
Harms and benefits
According to that article, aspergillosis can stick to the upper airways for many days and can be contained with antifungals. But once it invades the blood vessels of the lungs, mortality exceeds 80%, even when systemic antifungal therapy is applied.
Candidiasis, which is suffered almost exclusively by patients hospitalized in ICUs, is not more frequent in patients with covid-19 than in those hospitalized for other reasons. However, fungi of a new emerging species, Candida auris, are of concern, as they are capable of colonizing the skin. They also seem to be the only ones transmitted from person to person. This species is resistant to all known antifungals and, because it is present in various environments, it can easily reach patients with catheters, respirators and other invasive life support devices in hospitals
Meanwhile, covid-19-associated mucormycosis (CAM) is a serious problem, particularly in India, where the number of cases doubled compared to the pre-pandemic period. Reports of this mycosis gained international attention in 2021, when more than 47,500 cases were reported in that country between the months of May and August alone. At that time, the Indian government considered mucormycosis an epidemic, which was erroneously called “black fungus”, due to the appearance of the human tissue necrotic due to the disease. To tell the truth, the black fungi are part of another group, relatively distant from the Mucorales, and do not cause disease in humans.
In patients with covid-19, mucormycosis usually appears in the area of the eyes and nose, and can reach the brain. In these cases, the association of both diseases has a mortality of 14%. Because it causes necrosis, in many cases this infection requires surgeries that disfigure patients. When they survive, they can lose parts of their faces and have to deal with various problems for the rest of their lives. When the fungal infection affects the lungs or spreads throughout the body, mortality reaches 80%.
“The prevalence of this fungal infection in India was 0.27% in hospitalized COVID-19 patients, although it can occur frequently in patients outside hospitals, such as those treated at home with very high doses of readily available systemic corticosteroids. for the population of that country”, comments Hönigl.
The use of this and other types of drugs that suppress immune activity is one of the causes of the increase in fungal infections worldwide. However, this strategy has proven successful during the pandemic, as the benefits have outweighed the risks. Even so, the researchers warn about the importance of avoiding the abusive administration of immunosuppressive drugs.
Alternatively, during the pandemic, some centers subject to high risk of aspergillosis successfully implemented antifungal prophylaxis, by administering drugs even before infection with those agents. But since fungi are often resistant to most available drugs and there are not enough clinical studies to evaluate this strategy, it is not currently recommended.
“Immunosuppressants are a great advance in medicine, as they make it possible for many people to stop dying of cancer and autoimmune diseases, and even allow them to receive organs from other people,” says Goldman.
“As a side effect, its application greatly increased the incidence of fungal infections. Except for some that are thermotolerant, such as A. fumigatus fungi normally do not support the body temperature of mammals and our innate immunity fights them easily, but due to the decrease in immune activity to deal with highly inflammatory diseases such as covid-19, a flank is opened for them to attack, ”he says .
new drugs
Global warming also opens the way for many fungi to adapt to higher temperatures, making humans more vulnerable. For this reason, specialists agree that it is urgent to develop new antifungal drugs. Currently, there are only four types of these drugs, compared to dozens of different classes of antibacterials, for example.
Another problem lies in the difficulty of making diagnoses, which may be too expensive for the standards of low- and middle-income countries or may not be carried out quickly enough to indicate the ideal treatment.
To ensure with 100% certainty of the existence of aspergillosis, for example, it is necessary to carry out a bronchoscopy study, a procedure considered too risky during the covid-19 pandemic. It happens that the amount of human fluids expelled during the procedure is more than enough to transmit SARS-CoV-2 to the medical team and that is why its application was avoided. This suggests that the statistics on that infection are underestimated.
“Fortunately, there is good news emerging in terms of drug development in this area, with several new classes of antifungals now in the process of phase II and III clinical trials,” says Hönigl.
Still, researchers fear that these new drugs will not reach all who need them, and that cutting-edge treatments will continue to be restricted to rich countries, thus continuing the current inequality in drug availability. those medications.
“Given this panorama of global warming, of few available drugs and of diseases that weaken and cause epidemics and pandemics, outbreaks of fungal infections will occur again. It is urgent to have more tools to control them and more researchers to study the different fungi and their mechanisms of action”, concludes Goldman.