Clinical Guidance for the Diagnosis and Treatment of COVID-19-Associated Pulmonary Aspergillosis

The European Commission on Medical Mycology (ECMM) and International Society for Human and Animal Mycology (ISHAM) released clinical guidance and research criteria for managing invasive pulmonary aspergillosis (IPA) among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was reviewed in a manuscript published in Lancet Infection.

Direct damage to epithelium in the respiratory tract from infection with SARS-CoV-2 enables Aspergillus speciesinvasion. Since the onset of the global pandemic, rising cases of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been observed. There is urgent need for increased awareness and further research into CAPA, as patients with CAPA have had higher rates of mortality compared with Aspergillus-free patients (44% vs 19%).

CAPA diagnosis can be difficult because these patients may not exhibit host factors or radiological features typical of invasive fungal disease. Typical diagnostic procedures, such as bronchoscopy, have been avoided to reduce health care worker exposure to aerosols.

CAPA Diagnosis

Proven CAPA: Relies on histological data alone, in which lung biopsy tissue indicates invasive growth of Aspergillus speciesobserved through microscopy, tissue culture, or by genetic testing through polymerase chain reaction (PCR).

Probable CAPA: Combines imaging and microbiology data. Evidence of pulmonary infiltrate and/or cavitating infiltrate are not typical features of COVID-19 and should trigger an investigation for IPA. Several avenues of microbiology evidence may be found from bronchoalveolar lavage testing, which through microscopy, culture, or PCR indicates evidence of Aspergillus species. Blood serum may also be tested by PCR, but additional evidence or 2 positive tests are needed for a probable CAPA diagnosis.

Possible CAPA: Based on a combination of imaging, microbiology, and clinical features. In addition to the imaging evidence described above, non-bronchoalveolar lavage testing with microscopy, culture, or PCR evidence of Aspergillus species should be combined with refractory fever, pleural rub, chest pain, or hemoptysis symptoms for possible CAPA diagnosis.

CAPA Treatment

The primary drug choice should be voriconazole or isavuconazole. In the case of treatment failure or azole resistant Aspergillus, liposomal amphotericin B should be the second-line therapeutic.

All patients treated with voriconazole should be monitored by a plasma trough for appropriate concentrations (2 to 6 mg/L) and patients treated with liposomal amphotericin B should be continuously monitored for renal and hepatic functioning.

Despite these recent clinical guidelines for the diagnosis and management of CAPA, future studies and clinical trials are needed to establish differential features between airway colonization and invasive infection, between tracheobronchitis and pulmonary phenotypes, to determine important host factors and immunological defense, and to streamline diagnosis and management guidelines.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance. Lancet Infect Dis. Published online December 14, 2020. doi:10.1016/S1473-3099(20)30847-1.