COVID Impacts

COVID-19-associated fungal infections can lead to severe illness and death. COVID-19 likely increases the risk for fungal infections because of its effect on the immune system and because treatments for COVID-19 (like steroids and other drugs) can weaken the body’s defenses against fungi. The most commonly reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis (sometimes referred to by the misnomer ”black fungusexternal icon.”) Fungal infections resistant to antifungal treatment have also been described in patients with severe COVID-19.

Moreover, a distinctive immune-cell event that is observed in patients with COVID-19 is the decrease of T-cell populations, especially in patients with severe disease. Decline of lymphocyte counts can be accompanied by defective function. Severe lymphepenia has been established as a factor predicting the risk of invasive mold disease in patients with hematological malignancies.

Fungal infections of the paranasal sinuses are in fact a spectrum of diseases rather than one distinct entity. As such, there has been much published on the classification of fungal rhinosinusitis (FRS). These are invasive or non-invasive, dependent on the potential of the fungal hyphae to invade the tissues through the epithelium (invasive) in comparison to the infection being confined to the superficial epithelium (non-invasive). As its name suggests, invasive FRS can result in dramatic tissue invasion through mucosa, bone, neurovascular structures and surrounding organs.

Systemic corticosteroids have been proven to reduce mortality in specific subgroups of patients with COVID‐19, with the greatest efficacy observed in individuals who require invasive mechanical breathing. Nonetheless, systemic corticosteroids depress the immune system, predisposing patients to invasive fungal rhinosinusitis. This results in a high rate of deadly fungal infection affecting the nose and paranasal sinuses, with the rhino–orbito–cerebral presentation being the most prevalent.

The COVID‐19‐associated AIFR differs from that of the non‐COVID‐19 in both existences of some remarkable risk factors and high incidence rate. The upregulation of inflammatory cytokines and reduced cell‐mediated immunity with decreasing levels of CD4⁺ and CD8⁺ cells might both be related to COVID‐19. Further contributing variables to the COVID‐19‐linked AIFR include steroid‐induced hyperglycemia, diabetic ketoacidosis, elevated iron levels, immunosuppression from COVID‐19, excessive steroid dosages, and immunomodulators, and reduced white blood cells phagocytic activity. Additionally, extended hospitalization with or without mechanical ventilators and low oxygen levels both increase the risk of AIFR. Compared to non‐COVID‐19 individuals, the incidence of AIFR is noticeably higher in immunocompromised, diabetic, renal, and hepatic dysfunction patients, as well as those with cardiac illnesses, bronchial asthma, and obesity.

Aspergillosis is a disease caused by Aspergillus, a common mold (a type of fungus) that lives indoors and outdoors. Most people breathe in Aspergillus spores every day without getting sick. However, people with weakened immune systems or lung diseases are at a higher risk of developing health problems due to Aspergillus. There are different types of aspergillosis. Some types are mild, but some of them are very serious.

Reports of COVID-19-associated pulmonary aspergillosis have raised concerns about it worsening the disease course of COVID-19 and increasing mortality. Additionally, the first cases of COVID-19-associated pulmonary aspergillosis caused by azole-resistant aspergillus have been reported.

Scientists are still learning about aspergillosis (infections caused by the fungus Aspergillus) in people with severe COVID-19. In the past, scientists thought aspergillosis occurred almost entirely in people with severely weakened immune systems. However, aspergillosis has been increasingly reported in patients without weakened immune systems but who have severe respiratory infections caused by viruses, including influenza. Several recent reports describe COVID-19-associated pulmonary aspergillosis (CAPA).

Mucormycosis (previously called zygomycosis) is a rare but serious angio-invasive infection caused by a group of fungi called mucormycetes. 

Mucormycosis mainly affects people who are immunocompromised, or patients already infected with other diseases. High risk groups include people with diabetes (especially diabetic ketoacidosis), solid organ transplantation, neutropenia (low neutrophils, a type of white blood cells), long-term systemic corticosteroid use, and iron overload (hemochromatosis). The risk is high for people living with HIV, and those using immunomodulating drugs, including the anti-fungal voriconazole in some high-risk groups. 

Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes.

COVID-19-associated mucormycosis is a major public health problem in India. COVID-19-associated mucormycosis cases have also been seen outside of India, including in the United States, although much less commonly. Uncontrolled diabetes and overuse of steroids for COVID-19 treatment are important risk factors.

Candida auris (C. auris) is a type of fungus that can cause serious illness in hospitalized patients. Infections with this fungus can be difficult to treat. C. auris only recently appeared in the United States, and public health officials are researching more about how it is spread.

Candida auris (C. auris) is an emerging fungus that can cause outbreaks of severe infections in healthcare facilities. In the United States, it has most commonly spread in long-term care facilities caring for people with severe medical conditions. However, since the start of the COVID-19 pandemic, outbreaks of C. auris have been reported in COVID-19 units of acute care hospitals. These outbreaks may be related to changes in routine infection control practices during the COVID-19 pandemic, including limited availability of gloves and gowns, reuse or extended use of these items, and changes in cleaning and disinfection practices. Screening for C. auris colonization, an important part of containment efforts, has been more limited as healthcare facilities and health departments have been responding to COVID-19.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide.

According to a CDC analysis published in April 2023 in Annals of Internal Medicine, clinical cases of C. auris, grew 95 percent from 2020 to 2021. Overall, 3,270 infections were reported in the U.S. from 2016 — when the first clinical case was reported — through 2021. Additionally, the number of cases that were resistant to antifungal drugs tripled from 2019 to 2021. Infections in the US increased from 476 clinical cases in 2019 to 1,471 in 2021.

Invasive candidiasis is an infection caused by a yeast (a type of fungus) called Candida.  Unlike Candida infections in the mouth and throat (also called “thrush”) or vaginal “yeast infections,” which are localized to one part of the body,  invasive candidiasis is a serious infection that can affect the blood, heart, brain, eyes, bones, or other parts of the body.

Candida can enter the bloodstream or internal organs and cause an infection. A Candida bloodstream infection, also called candidemia, is the most common form of invasive candidiasis. In the United States, candidemia is one of the most common causes of bloodstream infections in hospitalized patients, and it often results in long hospital stays and death. It is also responsible for high medical costs.

Patients hospitalized for COVID-19 are at risk for healthcare-associated infections (HAIs), including candidemia, or bloodstream infections caused by Candida. Patients with COVID-19 who developed candidemia were less likely to have certain underlying conditions and procedures commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including medicines that suppress the immune system.