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Aspergillus in Critically Ill COVID-19 Patients: A Scoping Review
Erlangga Yusuf1, Leonard Seghers2, Rogier A S Hoek2
1Department of Medical Microbiology and Infectious Disease, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Abstract:
Several reports have been published on Aspergillus findings in COVID-19 patients leading to a proposition of new disease entity COVID-19-associated pulmonary aspergillosis. This scoping review is designed at clarifying the concepts on how the findings of Aspergillus spp. in COVID-19 patients were interpreted. We searched Medline to identify the studies on Aspergillus spp. findings in COVID-19 patients. Included were observational studies containing the following information: explicit mention of the total number of the study population, study period, reason for obtaining respiratory samples, case definition, and clinical outcomes. Excluded were case series, case reports and reviews. Identified were 123 publications, and 8 observational studies were included. From the included studies the following issues were identified. The proportion of immunocompromised patients considered as host factors varied from 0 to 17%. Most of the studies did not mention radiographic findings explicitly. Respiratory samples were mostly obtained to investigate clinical deterioration. Aspergillus culture, antigen or PCR testing on bronchoalveolar lavage (BAL) fluid were performed in between 23.3% and 66.3% of the study population. Two studies performed periodic samples of BAL. Galactomannan index (GI) positivity in BAL was between 10% and 28%. GI in blood was found in 0.9% to 6.7% of the available samples. The prevalence of COVID-19-associated pulmonary aspergillosis ranged from 2.7% to 27.7%. Studies compared the mortality between defined cases and non-cases, and all showed increased mortality in cases. No studies showed that antifungal treatment reduced mortality. Concluding, this review showed how studies defined the clinical entity COVID-19-associated pulmonary aspergillosis where positive Aspergillus test in the respiratory sample was the main driver for the diagnosis. There were many differences between studies in terms of test algorithm and Aspergillus test used that largely determined the prevalence. Whether antifungal therapy, either as prophylaxis, pre-emptive or targeted therapy will lead to better outcomes of COVID-19-associated pulmonary aspergillosis patients is still need to be answered.
Insights
This review clarifies COVID-19-associated pulmonary aspergillosis diagnosis. Positive Aspergillus tests in respiratory samples were key, but diagnostic methods varied, impacting prevalence and outcomes.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pulmonology
Background:
- Reports of Aspergillus findings in COVID-19 patients suggest a new disease entity: COVID-19-associated pulmonary aspergillosis.
- Interpretation of Aspergillus spp. findings in COVID-19 patients requires clarification.
- Existing literature lacks standardized diagnostic criteria for this condition.
Purpose of the Study:
- To clarify how Aspergillus spp. findings in COVID-19 patients were interpreted.
- To review diagnostic approaches and prevalence of COVID-19-associated pulmonary aspergillosis.
- To identify variations in diagnostic methods and their impact on reported outcomes.
Main Methods:
- Scoping review of observational studies identified via Medline search.
- Inclusion criteria: explicit data on study population, period, sample collection reason, case definition, and outcomes.
- Exclusion criteria: case series, case reports, and reviews.
Main Results:
- Eight observational studies were included, with 0-17% immunocompromised patients.
- Aspergillus testing (culture, antigen, PCR) on bronchoalveolar lavage (BAL) fluid varied (23.3%-66.3%).
- Prevalence of COVID-19-associated pulmonary aspergillosis ranged from 2.7% to 27.7%, with higher mortality in diagnosed cases.
- Galactomannan index positivity in BAL ranged from 10% to 28%; in blood, 0.9% to 6.7%.
- No studies demonstrated reduced mortality with antifungal treatment.
Conclusions:
- Diagnosis of COVID-19-associated pulmonary aspergillosis heavily relied on positive Aspergillus tests in respiratory samples.
- Significant heterogeneity in diagnostic algorithms and Aspergillus tests used across studies influenced prevalence estimates.
- The efficacy of antifungal therapy for COVID-19-associated pulmonary aspergillosis remains undetermined.
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