Invasive Aspergillosis and Mucormycosis in Patients With COVID-19

Dallas Smith, PharmD; Jeremy A. W. Gold, MD, MS


March 03, 2022

Editorial Collaboration

Medscape &

Invasive aspergillosis and mucormycosis are life-threatening infections caused by environmental molds. Invasive aspergillosis most often affects the lungs (pulmonary aspergillosis), while mucormycosis most often affects the sinuses, lungs, or skin.[1] Classic patient risk factors for these conditions include hematologic malignancies, stem cell or solid organ transplantation, and other forms of severe immunosuppression.[2,3] Uncontrolled diabetes is an important risk factor for mucormycosis.[2]

COVID-19 is likely to increase the risk for pulmonary aspergillosis and mucormycosis because of COVID-19–induced immune dysregulation and treatments for COVID-19 (eg, corticosteroids) that weaken host immune defenses against molds.[4,5] COVID-19–associated pulmonary aspergillosis (CAPA) and mucormycosis (CAM) have emerged globally as public health threats during the pandemic. Researchers estimate that CAPA might occur in more than 10% of mechanically ventilated COVID-19 patients.[5] In India, more than 40,000 CAM cases have been reported during the pandemic (as of July 2021), but this disease is rarer in other parts of the world. Both CAPA and CAM have been associated with mortality rates around 50%.[5,6] Recent reports from the Centers for Disease Control and Prevention (CDC) and partners highlight the emergence of CAM in the United States and globally outside of India.[7,8]

Here are five things to know about CAPA and CAM:

1. Look out for pulmonary aspergillosis and mucormycosis in patients with COVID-19.

This patient presented with a case of a periorbital fungal infection known as mucormycosis, caused by a member of the order, Mucorales. (PHIL #2831)

  • The signs and symptoms of CAPA may include fever, chest pain, cough, hemoptysis, and shortness of breath. Consider CAPA in the differential diagnosis of patients with severe COVID-19 who experience worsening respiratory function or sepsis.

  • The signs and symptoms of CAM usually include fever and can vary depending on the affected body site:

    • Rhino-orbital-cerebral: unilateral facial swelling, headache, sinus congestion, vision loss, proptosis, and necrotic lesions of the nasal bridge of the palate

    • Pulmonary: cough, chest pain, and shortness of breath

    • Cutaneous: blisters, or ulcers that become necrotic; and pain, erythema, or swelling around the wound

    • Gastrointestinal: abdominal pain, nausea, vomiting, and gastrointestinal bleeding

  • CAPA and CAM cases have been reported in patients who:

    • Are mechanically ventilated

    • Are receiving corticosteroids

    • Have poorly controlled diabetes (CAM)

    • Are receiving immunomodulating drugs such as tocilizumab

    • Lacked classic risk factors for mold infections such as cancer, stem cell or solid organ transplantation, and other forms of severe immunosuppression

CAPA is generally seen in patients with severe COVID-19, whereas CAM may also occur in patients whose COVID-19 is not severe.[7,9]

2. Learn how to test for CAPA and CAM.

This methenamine sliver-stained lung tissue specimen revealed numerous darkly stained filaments of an Aspergillus species fungal organism in a patient with aspergillosis. (PHIL #21199)

  • Aspergillosis can be challenging to diagnose because symptoms (eg, fever, cough, shortness of breath) are nonspecific and testing typically requires a specimen from bronchoscopy.[10,11] Aspergillosis is often diagnosed through strategic, prospective, multimodal testing. Cultures, histopathology, fungal biomarkers like Aspergillus galactomannan and 1,3-beta-D-glucan (BDG), and polymerase chain reaction (PCR) can be used in this approach. A positive result from a bronchoalveolar lavage fluid (BAL) sample is typically sufficient to confirm CAPA. A positive serum galactomannan or PCR probably indicates invasive aspergillosis, while a negative test does not rule out invasive aspergillosis. Sensitivity may be increased through dual testing with BDG.[5]

  • Suspected mucormycosis is an emergency that requires rapid diagnosis and treatment. CAM diagnostics typically begin with CT or MRI imaging to assess the extent of disease and tissue sampling for species identification and histopathologic analysis.[12] In resource-limited settings, direct microscopy can provide a useful and inexpensive tool for diagnosing mucormycosis. Aspergillus galactomannan and BDG assays are typically negative in patients with CAM.

3. If you suspect that a patient has mucormycosis or pulmonary aspergillosis, urgent antifungal therapy and surgery (if indicated) can be lifesaving.

  • Treatment for CAPA and CAM should not be delayed while obtaining imaging studies or awaiting confirmatory tests such as histopathology.

  • Recommended treatment for CAPA includes the use of broad-spectrum triazoles.[3,10] Voriconazole or isavuconazole is commonly used for 6-12 weeks; posaconazole is an alternative treatment. Clinicians should consider therapeutic drug monitoring and drug-drug interactions when prescribing triazoles; it should be noted that isavuconazole does not have an established trough. For treating triazole-resistant CAPA, clinicians could consider liposomal amphotericin B or combination therapy with a triazole plus an echinocandin.[10]

  • CAM treatment always requires systemic antifungal therapy and frequently requires surgical debridement of the affected site.[12] For rhino-orbital infections, surgery may involve removal of part of the jaw or an eye and generally requires consultation with an ear, nose, and throat (ENT) specialist. Liposomal amphotericin B is the first-line treatment, and dosing depends on site of involvement. Broad-spectrum triazoles may be used in patients with poor renal function. However, CAM can be caused by a variety of fungal genera, some of which have poor triazole activity in vitro. If using triazoles, speciation is important for appropriate treatment. Voriconazole does not have a role in CAM treatment and should be avoided.

4. You can decrease infection risk by helping your patients with diabetes to control their blood glucose and by prescribing corticosteroids judiciously.

  • Uncontrolled diabetes is an important and modifiable risk factor for CAM. Blood glucose levels should be monitored carefully in patients receiving corticosteroids.

  • Inappropriate use of steroids for COVID-19 treatment, both outpatient and inpatient, has been linked to both CAPA and CAM. According to the National Institutes of Health (NIH) COVID-19 treatment guidelines:

    • In patients who don't require hospitalization or supplemental oxygen, dexamethasone or other systemic steroids are not recommended as treatment for COVID-19.

    • In hospitalized patients who don't require supplemental oxygen, dexamethasone or other corticosteroids are not recommended for the treatment of COVID-19.

5. Encourage your patients to get vaccinated against COVID-19.

Perhaps the best way to prevent COVID-19–associated mold infections is to prevent COVID-19 in the first place. COVID-19 vaccines are highly safe and effective. Talking with your patients about the COVID-19 vaccine can help improve vaccination rates, particularly in patient populations with lower vaccination coverage.[13]


Fungal Diseases and COVID-19 (CDC)

Symptoms of Aspergillosis (CDC)

Symptoms of Mucormycosis (CDC)

Care Step Pathway for a Suspected Pulmonary COVID-19-Associated IFI (COVID-19-Associated Fungal Infections Education Initiative)

Corticosteroids (NIH COVID-19 Treatment Guidelines)