COVID-19 associated pulmonary aspergillosis: regional variation in incidence and diagnostic challenges

Prattes, Juergen; Köehler, Philipp; Hoenigl, Martin; Wauters, Joost; Giacobbe, Daniele Roberto; Lagrou, Katrien; Salmanton‐García, Jon; Rautemaa‐Richardson, Riina; Hatzl, Stefan; Maertens, Johan; Debaveye, Yves; Bourgeois, Marc; Reynders, Marijke; Rutsaert, Lynn; Regenmortel, N. Van; Lormans, Piet; Feys, Simon; Reisinger, Alexander Christian; Cornely, Oliver A.; Lahmer, Tobias; Valerio, Maricela; Delhaès, Laurence; Jabeen, Kauser; Steinmann, Joerg; Chamula, Mathilde; Bassetti, Matteo

doi:10.1007/s00134-021-06510-2

Cited by 34 publications

(30 citation statements)

References 5 publications

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“…Although the prevalence of CAPA in our ICU‐admitted patients (6.04%) is similar to other works 27 and is consistent with studies in our setting 31 and autopsy studies, 32 some other authors have noted a higher prevalence, 4,12,28,33 up to 30% 34 . These differences could be related to regional variations in incidence 35 . Using the same cut‐off of 6 points in a high prevalence population to identify patients at low risk would remain adequate, as it would identify patients with a risk of developing CAPA of approximately 1%.…”

Section: Discussionsupporting

confidence: 92%

“… 34 These differences could be related to regional variations in incidence. 35 Using the same cut‐off of 6 points in a high prevalence population to identify patients at low risk would remain adequate, as it would identify patients with a risk of developing CAPA of approximately 1%. Of note, in populations with a higher prevalence of CAPA, the cut‐off of 6 points would be enough to identify patients at high risk, since patients with 6 or more points would present a risk greater than 40%.…”

Section: Discussionmentioning

confidence: 99%

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COVID‐19‐associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID‐19 patients

Calderón-Parra

Mills-Sánchez

Moreno-Torres

et al. 2022

Mycoses

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Background: COVID-19-associated pulmonary aspergillosis (CAPA) is a major complication of critically ill COVID-19 patients, with a high mortality rate and potentially preventable. Thus, identifying patients at high risk of CAPA would be of great interest.We intended to develop a clinical prediction score capable of stratifying patients according to the risk for CAPA at ICU admission.Methods: Single centre retrospective case-control study. A case was defined as a patient diagnosed with CAPA according to 2020 ECMM/ISHAM consensus criteria. 2 controls were selected for each case among critically ill COVID-19 patients.Results: 28 CAPA patients and 56-matched controls were included. Factors associated with CAPA included old age (68 years vs. 62, p = .033), active smoking (17.9% vs. 1.8%, p = .014), chronic respiratory diseases (48.1% vs. 26.3%, p = .043), chronic renal failure (25.0% vs. 3.6%, p = .005), chronic corticosteroid treatment (28.6% vs. 1.8%, p < .001), tocilizumab therapy (92.9% vs. 66.1%, p = .008) and high APACHE II at ICU admission (median 13 vs. 10 points, p = .026). A score was created including these variables, which showed an area under the receiver operator curve of 0.854 (95% CI 0.77-0.92). A punctuation below 6 had a negative predictive value of 99.6%. A punctuation of 10 or higher had a positive predictive value of 27.9%. Conclusion:We present a clinical prediction score that allowed to stratify critically ill COVID-19 patients according to the risk for developing CAPA. This CAPA score would allow to target preventive measures. Further evaluation of the score, as well as the utility of these targeted preventive measures, is needed.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

COVID‐19‐associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID‐19 patients

Calderón-Parra

Mills-Sánchez

Moreno-Torres

et al. 2022

Mycoses

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“…Finally, the study chose a more conservative approach to CAPA classification by applying the new and more restrictive ECMM/ISHAM criteria for CAPA classification instead of the modified Blot criteria. When compared to modified Blot criteria, application of these new criteria was shown to result in a reduction of the mean incidence of probable/proven CAPA cases from 19% to 11.9% among evaluable cases, bringing the prevalence of CAPA cases closer to that suggested by autopsy studies (30,31).…”

Section: Discussionmentioning

confidence: 96%

Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA): a Multicenter Study

et al. 2022

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This multicenter study evaluated the IMMY Aspergillus Galactomannan Lateral Flow Assay (LFA) with automated reader for diagnosis of pulmonary aspergillosis in patients with COVID-19 associated acute respiratory failure (ARF) requiring intensive care unit (ICU) admission between 03/2020 and 04/2021. A total of 196 respiratory samples and 148 serum samples (n=344) from 238 patients were retrospectively included, with a maximum of one of each sample type per patient. Cases were retrospectively classified for COVID-19 associated pulmonary aspergillosis (CAPA) status following the 2020 consensus criteria, with the exclusion of LFA results as a mycological criterion. At the 1.0 cutoff, sensitivity of LFA for CAPA (proven/probable/possible) was 52%, 80% and 81%, and specificity was 98%, 88% and 67%, for bronchoalveolar lavage fluid (BALF), non-directed bronchoalveolar lavage (NBL), and tracheal aspiration (TA), respectively. At the 0.5 manufacturer’s cutoff, sensitivity was 72%, 90% and 100%, and specificity was 79%, 83% and 44%, for BALF, NBL and TA, respectively. When combining all respiratory samples, the receiver operating characteristic (ROC) area under the curve (AUC) was 0.823, versus 0.754, 0.890 and 0.814 for BALF, NBL and TA, respectively. Sensitivity and specificity of serum LFA were 20% and 93%, respectively, at the 0.5 ODI cutoff. Overall, the Aspergillus Galactomannan LFA showed good performances for CAPA diagnosis, when used from respiratory samples at the 1.0 cutoff, while sensitivity from serum was limited, linked to weak invasiveness during CAPA. As some false positive results can occur, isolated results slightly above the recommended cutoff should lead to further mycological investigations.

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“…During the COVID-19 pandemic, there was a surge in the reliance on nonbronchoscopic lavage (NBL) and tracheal aspirates to perform the fungal work-up rather than bronchoalveolar lavage, due to safety concerns [8]. Most of the fungal diagnostic tools have not been validated for these types of respiratory specimen, and using them may, as such, have led to an overestimation of the CAPA incidence (misidentifying colonization and invasion) [62]. Regional variation in number of inclusions and CAPA incidence in studies with observational data.…”

Section: Incidencementioning

confidence: 99%

A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA)

Feys

Almyroudi

Braspenning

et al. 2021

JoF

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Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a severe fungal infection complicating critically ill COVID-19 patients. Numerous retrospective and prospective studies have been performed to get a better grasp on this lethal co-infection. We performed a qualitative review and summarized data from 48 studies in which 7047 patients had been included, of whom 820 had CAPA. The pooled incidence of proven, probable or putative CAPA was 15.1% among 2953 ICU-admitted COVID-19 patients included in 18 prospective studies. Incidences showed great variability due to multiple factors such as discrepancies in the rate and depth of the fungal work-up. The pathophysiology and risk factors for CAPA are ill-defined, but therapy with corticosteroids and anti-interleukin-6 therapy potentially confer the biggest risk. Sampling for mycological work-up using bronchoscopy is the cornerstone for diagnosis, as imaging is often aspecific. CAPA is associated with an increased mortality, but we do not have conclusive data whether therapy contributes to an increased survival in these patients. We conclude our review with a comparison between influenza-associated pulmonary aspergillosis (IAPA) and CAPA.

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COVID-19 associated pulmonary aspergillosis: regional variation in incidence and diagnostic challenges

Cited by 34 publications

References 5 publications

COVID‐19‐associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID‐19 patients

COVID‐19‐associated pulmonary aspergillosis (CAPA): Risk factors and development of a predictive score for critically ill COVID‐19 patients

Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA): a Multicenter Study

A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA)

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