Mature sporangium of a Mucor - Credit CDC PHIL
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Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection generally seen in severely ill, or immunocompromised patients. Patients taking immune suppressant drugs - such as organ transplant recipients - are at a higher risk of infection.
People get mucormycosis by coming in contact with the fungal spores in the environment. For example, infections involving the lung or sinus can occur after someone breathes in spores. These forms of mucormycosis usually occur in people who have health problems or take medicines that lower the body’s ability to fight germs and sickness.2,3
Types of mucormycosis
- Rhinocerebral (sinus and brain) mucormycosis is an infection in the sinuses that can spread to the brain. This is most common in people with uncontrolled diabetes and in people who have had a kidney transplant.4–5
- Pulmonary (lung) mucormycosis is the most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell transplant.
- Gastrointestinal mucormycosis is more common among young children than adults. Premature and low-birth-weight infants less than 1 month of age are at risk if they have had antibiotics, surgery, or medications that lower the body’s ability to fight germs and sickness.6-7
- Cutaneous (skin) mucormycosis occurs after the fungi enter the body through a break in the skin. This type of infection might occur after a burn, scrape, cut, surgery, or other types of skin trauma. This is the most common form of mucormycosis among people who do not have weakened immune systems.
- Disseminated mucormycosis occurs when the infection spreads through the bloodstream to affect another part of the body. The infection most commonly affects the brain, but also can affect other organs such as the spleen, heart, and skin.
Types of fungi that most commonly cause mucormycosis
Examples are Rhizopus species, Mucor species, Rhizomucor species, Syncephalastrum species, Cunninghamella bertholletiae, Apophysomyces species, and Lichtheimia (formerly Absidia) species.8
A year ago (see India Reporting Rare Cases of Mucormycosis In COVID Patients) we were seeing alarming reports out of India of thousands of COVID-related Mucormycosis (aka `Black Fungus') cases, many resulting in death.
Last summer, the American Society for Microbiology (ASM) published a highly informative article on the disease, and India's outbreak, titled COVID-19-Associated Mucormycosis: Triple Threat of the Pandemic), which cited 41,512 cases and 3,554 deaths over a six month period in India.
While the United States hasn't seen the sort of mucormycosis epidemic that India reported, some cases have arisen. Yesterday the CDC's MMWR ran two reports, one on cases here in the United States (Arkansas), and another on cases in Honduras.India has a high incidence of diabetes and pre-diabetes, and when combined with the liberal use of corticosteroids in treating COVID patients and potential immune disruptions from COVID itself, that appears to produce a large number of patients vulnerable to mucormycosis co-infection.
Notes from the Field: COVID-19–Associated Mucormycosis — Arkansas, July–September 2021
Weekly / December 17, 2021 / 70(50);1750–1751
Theresa M. Dulski, MD1,2; Megan DeLong, MPH2; Kelley Garner, MPH2; Naveen Patil, MD2,3; Michael J. Cima, PhD2; Laura Rothfeldt, DVM2; Trent Gulley, MPH2; Austin Porter, DrPH2,3; Keyur S. Vyas, MD3; Hazel K. Liverett, MD3; Mitsuru Toda, PhD4; Jeremy A.W. Gold, MD4,*; Atul Kothari, MD2,3,* (View author affiliations)View suggested citation
During September 17–24, 2021, three clinicians independently notified the Arkansas Department of Health (ADH) of multiple patients with mucormycosis after a recent diagnosis of COVID-19. To provide data to guide clinical and public health practice, ADH coordinated a statewide call on October 11, 2021 to infection preventionists for COVID-19–associated mucormycosis cases.
Mucormycosis is an uncommon but severe invasive fungal infection caused by molds in the order Mucorales. Mucormycosis typically affects persons with immunocompromising conditions such as a hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes (1). The emergence of COVID-19–associated mucormycosis has been described in other parts of the world, particularly in India, but has been infrequently reported in the United States (2–4). COVID-19 might increase mucormycosis risk because of COVID-19–induced immune dysregulation or associated treatments such as corticosteroids and immunomodulatory drugs (e.g., tocilizumab or baricitinib) that impair host defenses against molds (5).
A case of mucormycosis was defined as laboratory identification of Mucorales by culture, histopathology, or polymerase chain reaction in a patient with a clinical diagnosis of invasive mucormycosis.† Cases were considered COVID-19–associated if the patient received a positive reverse transcription–polymerase chain reaction or antigen test result for SARS-CoV-2 (the virus that causes COVID-19) during the 60 days preceding the mucormycosis diagnosis. Cases were reported to ADH using a standardized case report form, medical records, or oral report. Data were stored using Research Electronic Data Capture software (version 10.6.18; Vanderbilt University) (6) and linked to state vital records and state immunization and COVID-19 registries. Patient demographic characteristics, underlying conditions, clinical course, treatment, and clinical outcomes were examined. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§
Ten COVID-19–associated mucormycosis cases that occurred during July 12–September 28, 2021, were reported to ADH by six hospitals.¶ Nine patients lived in Arkansas, with patients representing each of the state’s five public health unit regions; one patient lived in a bordering state. Among all 10 patients, the median age was 57 years (range = 17–78 years), all patients were non-Hispanic White persons, seven were male, one had a history of solid organ transplantation, and one had a history of recent traumatic injury at the body site where mucormycosis later developed. Eight patients had diabetes; among these, the median hemoglobin A1c was 8.6% (range = 6.0%–14.3% [normal <5.7%]).** During hospitalization, three patients with diabetes experienced diabetic ketoacidosis. Mucormycosis clinical signs and symptoms included those that were rhino-orbital (four patients, including three with cerebral involvement), pulmonary (three), disseminated (two), and gastrointestinal (one).
The median interval from COVID-19 diagnosis to the first positive test result for mucormycosis was 18.5 days (range = 6–52 days). None of the patients had been vaccinated against COVID-19. COVID-19 treatment included supplemental oxygen therapy (eight patients), invasive mechanical ventilation (five), corticosteroids (nine), tocilizumab (two), and baricitinib (two). Five patients received surgical treatment to excise mucormycosis-affected tissue. Six of the 10 patients died during hospitalization or within 1 week of discharge.
The findings in this report are subject to at least two limitations. First, cases were identified using passive reporting, which could have missed some mucormycosis cases. Second, the definition of COVID-19–associated cases was limited to positive tests within 60 days preceding mucormycosis diagnosis, which could have missed some cases occurring outside this period.
The 10 reported COVID-19–associated mucormycosis cases occurred during a 79-day period (July 12–September 28, 2021) coinciding with a statewide surge in COVID-19 cases caused by the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant.†† By comparison, nine mucormycosis cases per year might be expected in Arkansas (population approximately 3,000,000)§§ based on the estimated U.S. incidence of mucormycosis hospitalizations (approximately three per 1,000,000 persons annually) (7). The reported COVID-19–associated mucormycosis cases might have occurred because of COVID-19–induced immune dysregulation or medical treatments (5).
Because of the severity of mucormycosis, it is important that clinicians maintain a high index of suspicion for COVID-19–associated mucormycosis, including in patients without severe immunocompromising conditions. Mucormycosis treatment guidelines recommend prompt antifungal therapy¶¶ and surgical intervention to improve outcomes (8).
Maintenance of glycemic control in patients with diabetes, guideline-based use of corticosteroids for COVID-19 treatment,*** and vaccination against COVID-19 should be encouraged. As a result of these reported cases, ADH sent an update on the statewide Health Alert Network (October 21, 2021) and nationwide Epi-X listserv (October 22, 2021) to improve mucormycosis prevention, diagnosis, and treatment. COVID-19–associated mucormycosis surveillance and case investigations are ongoing.
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Excerpts from the second report, from Honduras, follow:
Notes from the Field: Mucormycosis Cases During the COVID-19 Pandemic — Honduras, May–September 2021
Weekly / December 17, 2021 / 70(50);1747–1749
Homer Mejía-Santos1,*; Sandra Montoya2,*; Rafael Chacón-Fuentes3; Emily Zielinski-Gutierrez3; Beatriz Lopez3; Mariangeli F. Ning3; Nasim Farach3; Fany García-Coto4; David S. Rodríguez-Araujo4; Karla Rosales-Pavón1; Gustavo Urbina1; Ana Carolina Rivera1; Rodolfo Peña5; Amy Tovar5; Mitzi Castro Paz6; Roque Lopez6; Fabian Pardo-Cruz7; Carol Mendez7; Angel Flores7; Mirna Varela7; Tom Chiller8; Brendan R. Jackson8; Alexander Jordan8; Meghan Lyman8; Mitsuru Toda8; Diego H. Caceres8,9,†; Jeremy A. W. Gold8,† (View author affiliations)
(Excerpt)
Seventeen persons received a diagnosis of mucormycosis during May 5–September 6, 2021; these included 11 persons with COVID-19–associated cases (Figure). Mucormycosis was confirmed by direct microscopy (16 cases), fungal culture (13 cases), or histopathology (three cases). The demographic features, underlying conditions, and mucormycosis clinical signs and symptoms were similar between patients with and without COVID-19. Most patients were male (nine); the median age was 54 years (IQR = 32–68 years). Diabetes was the most common underlying condition (12 patients), and two patients had hematologic malignancies; no other underlying immunosuppressive medical conditions were noted. During hospitalization, none of the patients with diabetes experienced diabetic ketoacidosis. The most frequent mucormycosis clinical signs and symptoms were rhino-orbital (12 patients) and cutaneous (four patients). The median interval between hospital admission and first positive test result for mucormycosis was 7 days (range = -8 to 21 days). Among the 11 patients with COVID-19–associated mucormycosis cases, nine were unvaccinated against COVID-19; the median interval between COVID-19 diagnosis and the first positive test result for mucormycosis was 11 days (range = -12 to 58 days). Seven COVID-19 patients received supplemental oxygen therapy, nine received corticosteroids, and four received tocilizumab.
Ten of the 17 patients died during hospitalization, including eight of the 11 with COVID-19–associated mucormycosis; three patients remained hospitalized at the time of medical chart abstraction. Two of the seven surviving patients experienced major sequelae from mucormycosis, including facial disfiguration and limb loss.
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