COVID-19–Associated Pulmonary Aspergillosis, March–August 2020

Salmanton‐García, Jon; Sprute, Rosanne; Stemler, Jannik; Bartoletti, Michele; Dupont, Damien; Valerio, Maricela; García-Vidal, Carolina; Falces‐Romero, Iker; Machado, Marina; Villa, Sofía de la; Schroeder, Maria; Hoyo, Irma; Hanses, Frank; Ferreira-Paim, Kennio; Giacobbe, Daniele Roberto; Meis, Jacques F.; Gangneux, Jean‐Pierre; Rodríguez-Guardado, Azucena; Antinori, Spinello; Sal, Ertan; Malaj, Xhorxha; Seidel, Danila; Cornely, Oliver A.; Köehler, Philipp

doi:10.3201/eid2704.204895

Cited by 194 publications

(226 citation statements)

References 44 publications

(36 reference statements)

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“…15.2% incidence of CAPA in our ICU in the first wave is comparable to the 19.4% 3 and 21.4% 4 published recently from other Dutch 21%) 30,31. Whilst BDG testing is nonspecific, its sensitivity in the ICU population for invasive fungal disease has been shown to be high (88%) 34.…”

supporting

confidence: 78%

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

Meijer

Dofferhoff

Hoiting

et al. 2021

Mycoses

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Background COVID‐19–associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%–33.3% have been reported depending on the geographic area, with high (47%) mortality. Objectives Here, we describe a single‐centre prospective case series with CAPA cases from both the first (March‐May, n = 5/33) and second (mid‐September through mid‐December, n = 8/33) COVID‐19 wave at a 500‐bed teaching hospital in the Netherlands. Patients/Methods In the first COVID‐19 wave, a total of 265 SARS‐CoV‐2 PCR‐positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS‐CoV‐2 PCR‐positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected. Results We found a significant decrease in COVID‐19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%–50%). Moreover, we found environmental TR34/L98H azole‐resistant Aspergillus fumigatus isolates in two separate patients. Conclusions In this series, 19.7% (n = 13/66) of mechanically ventilated SARS‐CoV‐2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID‐19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS‐CoV‐2 therapy.

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supporting

confidence: 78%

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

Meijer

Dofferhoff

Hoiting

et al. 2021

Mycoses

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“…Interestingly, while case reports on positive Aspergillus tests in COVID-19 patients originate from 17 different countries [ 26 ], observational studies are mostly from France. There is a possibility that Aspergillus testing, especially the use of galactomannan, is more widespread in French ICUs than in other countries.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus in Critically Ill COVID-19 Patients: A Scoping Review

Yusuf

Seghers

Hoek

et al. 2021

JCM

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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.

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“…According to a recent case series involving 186 CAPA cases, GM levels were positive (i.e., GM index ≥ 1.0) in respiratory samples from 113 (60.8%) patients, including BAL samples from 63 (33.9%) patients and NBL from 22 (11.8%) [ 4 ]. Furthermore, GM was detected in serum or plasma from 29 (15.6%) CAPA patients.…”

Section: Key Questionsmentioning

confidence: 99%

“…The mortality rate was 51% compared to 28% in influenza patients without IAPA [ 3 ]. COVID-19 associated pulmonary aspergillosis (CAPA) has been reported to have a similar mortality rate of 52% [ 4 ]. However, there are clear differences between IAPA and CAPA, including different patients’ typology and comorbidities, viral lytic effects and tissue tropism, host immune response as well as performance of Aspergillus diagnostic tests.…”

Section: Introductionmentioning

confidence: 99%

Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis

et al. 2021

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Purpose Invasive pulmonary aspergillosis (IPA) is increasingly reported in patients with severe coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Diagnosis and management of COVID-19 associated pulmonary aspergillosis (CAPA) are challenging and our aim was to develop practical guidance. Methods A group of 28 international experts reviewed current insights in the epidemiology, diagnosis and management of CAPA and developed recommendations using GRADE methodology. Results The prevalence of CAPA varied between 0 and 33%, which may be partly due to variable case definitions, but likely represents true variation. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis, allowing for diagnosis of invasive Aspergillus tracheobronchitis and collection of the best validated specimen for Aspergillus diagnostics. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL positive patients, but the decision to treat depends on the patients’ clinical condition and the institutional incidence of CAPA. We recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients. Conclusion CAPA is a complex disease involving a continuum of respiratory colonization, tissue invasion and angioinvasive disease. Knowledge gaps including true epidemiology, optimal diagnostic work-up, management strategies and role of host-directed therapy require further study. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06449-4.

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COVID-19–Associated Pulmonary Aspergillosis, March–August 2020

Cited by 194 publications

References 44 publications

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

Aspergillus in Critically Ill COVID-19 Patients: A Scoping Review

Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis

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