COVID-19-associated pulmonary aspergillosis: an underdiagnosed or overtreated infection?

Abstract

Purpose of review: Coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) may concern up to one third of intensive care unit (ICU) patients. The purpose of this review is to discuss the diagnostic criteria, the pathogenesis, the risk factors, the incidence, the impact on outcome, and the diagnostic and therapeutic management of CAPA in critically ill patients.

Recent findings: The incidence of CAPA ranges 3--28% of critically ill patients, depending on the definition used, study design, and systematic or triggered screening. COVID-19 is associated with direct damage of the respiratory epithelium, immune dysregulation, and common use of immunosuppressive drugs which might promote Aspergillus respiratory tract colonization and invasion. Positive Aspergillus tests among COVID-19 critically patients might reflect colonization rather than invasive disease. CAPA usually appears during the second week after starting invasive mechanical ventilation and is independently associated with ICU mortality.

Summary: Further studies are needed to validate CAPA case definitions, to determine the accurate incidence of CAPA in comparison to adequate controls, and its evolution during the pandemic. A pro-active diagnostic strategy, based on risk stratification, clinical assessment, and bronchoalveolar lavage could be recommended to provide early antifungal treatment in patients with high probability of CAPA and clinical deterioration.

Box 1

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FIGURE 1

Pathogenesis of COVID-19-associated pulmonary aspergillosis. Factors promoting Aspergillus respiratory tract colonization and invasion in critically ill patients infected with SARS-CoV-2. ARDS, acute respiratory distress syndrome; COPD, chronic obstructive pulmonary disease; EORTC/MSGERC, European Organization for Research and Treatment of Cancer / Mycoses Study Group Education and Research Consortium; ICU, intensive care unit; IL-6, interleukin-6.

FIGURE 2

Diagnostic strategy for COVID-19-associated pulmonary aspergillosis in the ICU, based on recent recommendations. Systematic screening is suggested by the 2020 ECMM/ISHAM guidelines [^▪▪]. Diagnostic procedure triggered by clinical assessment or specific computed tomography lesions is recommended by an international taskforce of experts in the field [^▪▪]. ARDS, acute respiratory distress syndrome; BAL, bronchoalveolar lavage; CT, computed tomography; EORTC/MSGERC, European Organization for Research and Treatment of Cancer / Mycoses Study Group Education and Research Consortium; GM, galactomannan; IL-6, interleukin-6; MV, mechanical ventilation; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.