key: cord-0787548-cfj6uofo authors: Roman‐Montes, Authors. Carla M.; Martinez‐Gamboa, Areli; Diaz‐Lomelí, Paulette; Cervantes‐Sanchez, Axel; Rangel‐Cordero, Andrea; Sifuentes‐Osornio, Jose; Ponce‐de‐Leon, Alfredo; Gonzalez‐ Lara, M. Fernanda title: Accuracy of galactomannan testing on tracheal aspirates in COVID‐19‐associated pulmonary aspergillosis date: 2020-11-20 journal: Mycoses DOI: 10.1111/myc.13216 sha: dd3b8ff83113eba81b65ff597ea1c1f517e995f8 doc_id: 787548 cord_uid: cfj6uofo OBJECTIVE: Our aim was to evaluate the performance of two galactomannan assays (Platelia Aspergillus EIA, BioRadⓇ, and Aspergillus Galactomannan LFA, IMMYⓇ, Norman, OK, USA) in tracheal aspirate (TA) samples of consecutive critically ill patients with COVID‐19. METHODS: We included critically ill patients, performed GM‐EIA and GM‐LFA in TA and followed them until development of CAPA or alternate diagnosis. CAPA was defined according to the modified AspICU criteria in patients with SARS‐CoV‐2 infection. We estimated sensitivity, specificity, positive and negative predictive values for GM‐EIA, GM‐LFA, the combination of both or either positive results for GM‐EIA and GM‐LFA. We explored accuracy using different breakpoints, through ROC analysis and Youden index to identify the optimal cutoffs. We described antifungal treatment and 30‐day mortality. RESULTS: We identified 14/144 (9.7%) patients with CAPA, mean age was 50.35 (SD 11.9), the median time from admission to CAPA was eight days; 28.5% received tocilizumab and 30‐day mortality was 57%. ROC analysis and Youden index identified 2.0 OD as the best cut‐off, resulting in sensitivity and specificity of 57.1% and 81.5% for GM‐EIA and 60% and 72.6% for GM‐LFA, respectively. CONCLUSIONS: The diagnostic performance of galactomannan in tracheal aspirates improved after using a cutoff of 2 OD. Although BAL testing is the ideal test, centers with limited access to bronchoscopy may consider this approach to identify or rule out CAPA. Biosystems 7500 thermocycler (Applied Biosystems, Foster City, CA, USA) Biosystems, Foster City, 131 CA, USA) using primers and conditions described elsewhere] 6 . Laboratory procedures. TAs were received at the Clinical Microbiology Laboratory and processed for bacterial and fungal Accepted Article LFA (4.7 OD). Serum GM was not available for either. All were discharged and alive at 28 days 189 without antifungal treatment. Tracheal aspirate galactomannan performance. Evaluation of cutoffs for GM-EIA showed sensitivity and specificity of 64.3% and 63% when using a 192 cutoff of 0.8, a sensitivity and specificity of 64.3% and 68.5% when using a cutoff of 1, a sensitivity 193 and specificity of 57.1% and 78.5% when using a cutoff of 1.5 and a sensitivity and specificity of 194 57.1% and 81.5% respectively, when using a cutoff of 2 OD. Evaluation of cutoffs for GM-LFA showed a sensitivity and specificity of 80% and 41% when using a cutoff of 0.8, a sensitivity and 196 specificity of 80% and 48.4% when using a cutoff of 1, a sensitivity and specificity of 60% and 197 64.2% when using a cutoff of 1.5 and a sensitivity and specificity of 60% and 72%, when using a were positive using a cutoff value of 2 OD on the sensitivity was 81.2%, specificity was 63.1%, NPV 202 was 96.7%, and PPV 20.4% (Table 3) . in chest X rays. 30 We acknowledge this may lead to reduced specificity, which was a recognized 299 findings in chest CTs as the only abnormality 2 . A major limitation of this study is one shared with 300 many biomarker performance studies in IFIs where the lack of an ideal reference standard leads to 301 uncertainty when classifying the presence or absence of the disease. Accepted Article evaluating the outcome were blinded to the TA GM-EIA and GM-LFA results, reducing the risk of 306 bias. Also, we used the modified AspICU criteria as a reference standard, which was developed in a 307 similar population with IAPA. To our knowledge, this is the first study that evaluates GM testing in TA 308 samples and provides useful information for centers with limited access to bronchoscopies. Although CAPA was not clinically suspected in most patients, a prospective validation including at risk patients 310 results in a real-world estimate of diagnostic accuracy. Our results warrant additional validation, ideally comparing TA galactomannan directly with BAL. However, in center with no access to bronchoscopies, the use of TA GM with an optimal cut-off may 314 be a reasonable alternative considering high NPV that would allow excluding CAPA. We believe the elevated mortality in CAPA supports implementing bronchoscopies providing 316 adequate PPE. A recent study described a bronchoscopy simulation model in intubated patients to 317 evaluate droplet an aerosol release. The authors found several critical situations during the 318 procedure such as opening the closed respiratory circuit, the continued operation of the ventilator 319 and inserting and removal of the bronchoscope. In addition to appropriate PPE, they suggest 320 implementing measures to limit droplet an aerosol contamination which may be of value 31 . The diagnostic performance of galactomannan in tracheal aspirates to identify CAPA was improved 324 after using a cutoff of 2 OD. Although BAL testing is the recommended diagnostic method, centers 325 with limited access to bronchoscopy may consider this approach to identify or rule out CAPA. This article is protected by copyright. All rights reserved Invasive aspergillosis in patients 331 admitted to the intensive care unit with severe influenza: a retrospective cohort study Prevalence of putative invasive 334 pulmonary aspergillosis in critically ill patients with COVID-19 COVID-19-associated Pulmonary Aspergillosis COVID-19 associated pulmonary aspergillosis Confronting and mitigating the risk of Associated Pulmonary Aspergillosis (CAPA) Detection of 2019 -nCoV by RT-PCR Fatal Aspergillosis in a Patient with SARS 347 Who Was Treated with Corticosteroids Pulmonary 350 pathology of severe acute respiratory syndrome in Toronto The Emergence of the Middle East Respiratory 353 Invasive aspergillosis in patients 355 admitted to the intensive care unit with severe influenza: a retrospective cohort study Invasive Fungal Disease From the European Organization for Research and Treatment of 359 Cancer and the Mycoses Study Group Education and Research Consortium Paul E. Verweij M. Detection of Galactomannan in Broncho-362 Alveolar Lavage Fluids by Platelia Aspergillus Enzyme Immunoassay (BioRad Laboratories, 363 USA and Sanofi Diagnostics Galactomannan in 366 bronchoalveolar lavage fluid for diagnosis of invasive aspergillosis in non-hematological 367 patients Point-of-care diagnosis of 369 invasive aspergillosis in non-neutropenic patients Detection of invasive pulmonary aspergillosis in critically 373 ill patients by combined use of conventional culture, galactomannan Aspergillus specific nested polymerase chain reaction in a prospective pilot study CONVENTIONAL 378 CULTURE AND PCR FOR DIAGNOSIS OF INVASIVE PULMONARY ASPERGILLOSIS IN 379 BRONCHOALVEOLAR LAVAGE: A COHORT STUDY Lateral flow assays for diagnosing invasive pulmonary 381 aspergillosis in adult hematology patients: A comparative multicenter study Performance of Galactomannan, Beta-D-Glucan Aspergillus Lateral-Flow Device, Conventional Culture, and PCR Tests with Bronchoalveolar 385 Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis False positive bronchoalveolar 388 lavage galactomannan: Effect of host and cut-off value Potentially Triggers Galactomannan Positivity in Nonhematological Patients COVID-19-associated pulmonary aspergillosis 394 (CAPA) in patients admitted with severe COVID-19 pneumonia: An observational study from 395 Utility of Aspergillus Antigen Detection in 397 Specimens Other than Serum Specimens Diagnostic Tests for Pneumonia in Ventilated 400 Patients: Prospective Evaluation of Diagnostic Accuracy Using Histology as a Diagnostic Cold 401 Standard Incidence of invasive 403 pulmonary aspergillosis among critically ill COVID-19 patients Risk of infections in rheumatoid arthritis patients treated 406 with tocilizumab Incidence of serious respiratory infections in patients with 408 rheumatoid arthritis treated with tocilizumab COVID-19 associated pulmonary 411 aspergillosis (CAPA)-from immunology to treatment Clinical and Epidemiological 414 Characteristics of Patients Diagnosed With Covid-19 in a Tertiary Care Center This article is protected by copyright. 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