Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance

Abstract

Severe acute respiratory syndrome coronavirus 2 causes direct damage to the airway epithelium, enabling aspergillus invasion. 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. This article constitutes a consensus statement on defining and managing COVID-19-associated pulmonary aspergillosis, prepared by experts and endorsed by medical mycology societies. COVID-19-associated pulmonary aspergillosis is proposed to be defined as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Recommended first-line therapy is either voriconazole or isavuconazole. If azole resistance is a concern, then liposomal amphotericin B is the drug of choice. Our aim is to provide definitions for clinical research and up-to-date recommendations for clinical management of the diagnosis and treatment of COVID-19-associated pulmonary aspergillosis.

Figure 1

Defining and diagnosing CAPA (pulmonary form) Classification of possible CAPA will most likely be sufficient to initiate antifungal therapy in the clinic but, in line with other consensus statements, it is not recommended for enrolling patients into clinical trials. Additional studies are needed to confirm the specificity of non-bronchoscopic lavage testing. Bronchoalveolar lavage and non-bronchoscopic lavage are currently not considered equal for diagnosing CAPA. CAPA=COVID-19-associated aspergillosis. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. *Visual reader must be used for primary result and confirmatory galactomannan testing should be sought. † In case of patients with chronic obstructive pulmonary disease or chronic respiratory disease, the PCR or culture results should be confirmed by galactomannan testing to rule out colonisation or chronic aspergillosis. Galactomannan index must be available; galactomannan-index threshold applies to both enzyme immunoassay and lateral flow assay.

Figure 2

Defining and diagnosing CAPA (tracheobronchial form) CAPA=COVID-19-associated aspergillosis. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. *Visual reader must be used for primary result and confirmatory galactomannan testing should be sought. † In case of patients with chronic obstructive pulmonary disease or chronic respiratory disease, the PCR or culture results should be confirmed by galactomannan testing to rule out colonisation or chronic aspergillosis. Galactomannan index must be available; galactomannan-index threshold applies to both enzyme immunoassay and lateral flow assay.

Figure 3

Recommended treatment for CAPA CAPA=COVID-19-associated pulmonary aspergillosis. *The optimal duration is unknown, but the expert panel suggests 6–12 weeks as a treatment course. In immunocompromised patients (eg, with haematological malignancy or receiving immunosuppressive therapy), longer treatment might be necessary. † Salvage therapy: caspofungin 70 mg loading dose on the first day followed by 50 mg/day. If body weight is more than 80 kg, then 70 mg loading dose on the first day followed by 70 mg/day.