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PMC:7265874 JSONTXT 17 Projects

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Id Subject Object Predicate Lexical cue
T1 0-52 Sentence denotes COVID-19-associated invasive pulmonary aspergillosis
T2 54-68 Sentence denotes To the Editor:
T3 69-205 Sentence denotes Since March 2020, following in the footsteps of China, Europe has been facing the COVID-19 pandemic, caused by the SARS-COV-2 virus [1].
T4 206-395 Sentence denotes Increasing numbers of patients are being admitted to intensive care units (ICU) throughout the world, imposing multiple diagnostic and therapeutic challenges on stressed healthcare systems.
T5 396-537 Sentence denotes In our 24-bedded mixed ICU, we have encountered an unexpectedly high number of COVID-19 patients developing invasive pulmonary aspergillosis.
T6 538-755 Sentence denotes Through our case series, we aim to raise awareness of this severe complication in the critical care community, point out different diagnostic obstacles and share our approach to the management of this complex problem.
T7 756-953 Sentence denotes Invasive pulmonary aspergillosis (IPA) is a well-known complication in immunocompromised patients and is encountered frequently in haematopoietic stem cell or solid organ transplant recipients [2].
T8 954-1101 Sentence denotes Continued improvement in diagnostics has revealed that half of the cases of IPA occur in the ICU, in patients who are often non-neutropenic [3, 4].
T9 1102-1270 Sentence denotes Severe influenza infection is a well-known risk factor for developing IPA in non-neutropenic patients; a syndrome termed influenza-associated aspergillosis (IAA) [4–6].
T10 1271-1429 Sentence denotes A damaged respiratory epithelium, dysfunctional mucociliary clearance and a local immune paralysis were demonstrated to be key pathophysiological factors [4].
T11 1430-1606 Sentence denotes Supported by the hypothesis that alveolar damage facilitates fungal invasion, acute respiratory distress syndrome (ARDS) has frequently been associated with IPA in the ICU [6].
T12 1607-1704 Sentence denotes With this in mind, the existence of COVID-19-associated pulmonary aspergillosis is deemed likely.
T13 1705-1850 Sentence denotes Between March 12th and April 25th 2020, 34 COVID-19 patients were admitted to our ICU, of whom 20 (59%) required invasive mechanical ventilation.
T14 1851-1924 Sentence denotes Seven of these ventilated patients (35%) were suspected of IPA (Table 1).
T15 1925-1999 Sentence denotes Median age in our patient cohort was 66 (interquartile range 56–77) years.
T16 2000-2055 Sentence denotes Underlying comorbidities were primarily cardiovascular.
T17 2056-2099 Sentence denotes Only three patients were immunocompromised.
T18 2100-2430 Sentence denotes One patient received chronic corticosteroid treatment for pemphigus foliaceous, one patient was HIV-positive (CD4 count > 250; viral load < 20 copies, treated with antiretrovirals [lamivudine/tenofovir/nevirapine]) and one patient had been treated for acute myeloid leukaemia 8 years ago and had developed IPA during chemotherapy.
T19 2431-2520 Sentence denotes All patients were intubated and mechanically ventilated due to severe COVID-19 pneumonia.
T20 2521-2556 Sentence denotes Table 1 Patients with suspected IPA
T21 2557-2884 Sentence denotes Patient ID Sex (M/F) Age Medical history Time between COVID-19 symptoms and ICU admission (days) Time between COVID-19 symptoms and intubation (days) Time between intubation and first finding of IPA (days) First BAL galactomannan index Peak BAL galactomannan index First serum galactomannan index Peak serum galactomannan index
T22 2885-2925 Sentence denotes 1 M 86 Hyperchol 7 7 9 N/A N/A 0.10 0.10
T23 2926-2979 Sentence denotes 2 M 38 Obesity, hyperchol 9 9 6 2.40 > 2.80 0.30 0.30
T24 2980-3016 Sentence denotes 3 M 62 DM 7 7 16 0.72 2.00 0.20 0.20
T25 3017-3080 Sentence denotes 4 M 73 DM, obesity, AHT, hyperchol 9 10 5 2.65 > 2.80 0.10 0.10
T26 3081-3148 Sentence denotes 5 M 77 DM, CKD, AHT, pemphigus foliaceus 9 10 2 2.79 2.79 0.10 0.10
T27 3149-3202 Sentence denotes 6 M 55 HIV, AHT, hyperchol 8 9 13 0.69 0.69 0.18 0.80
T28 3203-3249 Sentence denotes 7 M 75 AML, IPA (2012) 3 3 8 2.63 2.63 N/A N/A
T29 3250-3405 Sentence denotes Patient ID Sex (M/F) Age Medical history First positive culture CT scan Histological examinationa IPA diagnosis AspICU algorithm Antifungal therapy Outcome
T30 3406-3486 Sentence denotes 1 M 86 Hyperchol A. flavus (ETA) No scan available N/A – – None Died, ICU day 10
T31 3487-3611 Sentence denotes 2 M 38 Obesity, hyperchol A. fumigatus (BAL) + Positive Proven Absolute Voriconazole, isavuconazole Alive on MV, ICU day 28b
T32 3612-3713 Sentence denotes 3 M 62 DM A. fumigatus (BAL) No scan available Positive Proven Absolute Voriconazole Died, ICU day 20
T33 3714-3848 Sentence denotes 4 M 73 DM, obesity, AHT, hyperchol A. fumigatus (BAL) No scan available Positive Proven Absolute Voriconazole Alive on MV, ICU day 24b
T34 3849-3989 Sentence denotes 5 M 77 DM, CKD, AHT, pemphigus foliaceus A. fumigatus (BAL) No scan available Positive Proven Absolute Voriconazole Alive on MV, ICU day 21b
T35 3990-4099 Sentence denotes 6 M 55 HIV, AHT, hyperchol Negative No scan available Negative – Voriconazole, isavuconazole Died, ICU day 27
T36 4100-4194 Sentence denotes 7 M 75 AML, IPA (2012) A. fumigatus (BAL) No scan available N/A – Voriconazole Died, ICU day 8
T37 4195-4289 Sentence denotes CKD chronic kidney disease, AML acute myeloid leukaemia, IPA invasive pulmonary aspergillosis.
T38 4290-4499 Sentence denotes N/A no sample available, Hyperchol hypercholesterolaemia, AHT arterial hypertension, DM diabetes mellitus, BAL bronchoalveolar lavage, ETA endotracheal aspirate, MV mechanical ventilation arterial hypertension
T39 4500-4576 Sentence denotes aAnatomopathological examination of tissue samples obtained via bronchoscopy
T40 4577-4600 Sentence denotes bAt the time of writing
T41 4601-4753 Sentence denotes Our suspicion was raised initially through an unusually rapid growth (< 48 h) of Aspergillus species in bronchial aspirates of three different patients.
T42 4754-4902 Sentence denotes All samples were obtained during routine bronchoscopies, performed for atelectasis, respiratory deterioration or increasing inflammatory parameters.
T43 4903-5125 Sentence denotes From that moment, routine galactomannan assays on serum and bronchoalveolar lavage (BAL) fluid were assessed regularly and bronchoscopy-guided biopsies of suspicious tracheobronchial lesions were obtained whenever present.
T44 5126-5369 Sentence denotes Unfortunately, computed tomography (CT) scanning was deemed unfeasible in some patients due to extreme hypoxia or difficult mechanical ventilation and whenever performed, the distinction between COVID-19 and Aspergillus lesions proved complex.
T45 5370-5457 Sentence denotes Table 1 shows the timing and results of the microbiological testing in our case series.
T46 5458-5563 Sentence denotes Differentiating between Aspergillus colonization and IPA is notoriously difficult, especially in the ICU.
T47 5564-5803 Sentence denotes In the absence of host factors, as defined by the European Organisation for Research and Treatment of Cancer (EORTC) diagnostic criteria, invasive or high-risk diagnostics (biopsy, CT scan) are required to support the diagnosis of IPA [7].
T48 5804-5893 Sentence denotes The AspICU algorithm was designed to partially deal with the absence of host factors [6].
T49 5894-6017 Sentence denotes Based on this algorithm, four patients (No 2, 3, 4, 5) were diagnosed with proven IPA, based on histopathological evidence.
T50 6018-6091 Sentence denotes All of these patients showed positive galactomannan indices on BAL fluid.
T51 6092-6249 Sentence denotes In two patients, cultures and/or galactomannan BAL only became positive post mortem (No 1, 7), before CT scan or histopathological samples could be obtained.
T52 6250-6407 Sentence denotes In one patient (No 6), histopathological sampling was negative and galactomannan BAL only mildly raised, but a raised serum galactomannan was later detected.
T53 6408-6491 Sentence denotes In the remaining patients, the serum galactomannan index remained negative (< 0.5).
T54 6492-6603 Sentence denotes The mean time between intubation date and the first microbiological signs of IPA was a striking 8 (SD 5) days. 
T55 6604-6785 Sentence denotes ICU physicians often have to weigh the risks of further diagnostic tests against a delayed initiation of antifungal treatment, which is associated with mortality rates over 65% [6].
T56 6786-7012 Sentence denotes Because all patients with clinical features of possible IPA were suffering from severe respiratory failure and hemodynamic instability, we initiated antifungal therapy as soon as cultures or galactomannan assays were positive.
T57 7013-7056 Sentence denotes Five patients were started on voriconazole.
T58 7057-7227 Sentence denotes In two of these patients, the treatment was escalated to isavuconazole due to pancytopenia or undetectable voriconazole levels under continuous renal replacement therapy.
T59 7228-7259 Sentence denotes Two patients died on treatment.
T60 7260-7367 Sentence denotes To confirm and control this alarming incidence of COVID-19-associated IPA, a number of measures were taken.
T61 7368-7497 Sentence denotes Firstly, we ruled out an environmental source, by sampling room air and the oxygen and pressurized air supplies (MAS 100, Merck).
T62 7498-7566 Sentence denotes Prior to COVID-19, the incidence of IPA in our ICU was not elevated.
T63 7567-7686 Sentence denotes Nonetheless, high-efficiency particulate air filters (HEPA) (Halton Vita, Helsinki, Finland) were installed in the ICU.
T64 7687-7826 Sentence denotes Secondly, all mechanically ventilated COVID-19 patients were screened systematically by performing serum galactomannan assays twice weekly.
T65 7827-7970 Sentence denotes Whenever a bronchoscopy was needed, BAL galactomannan indices and mould cultures were requested, regardless of the indication for bronchoscopy.
T66 7971-8181 Sentence denotes Finally, we initiated prophylactic nebulization of 12.5 mg of liposomal amphotericin B (Ambisome®, Gilead, Foster City, USA) in every mechanically ventilated patient without an established diagnosis of IPA [8].
T67 8182-8294 Sentence denotes Since the implementation of these measures, we have not encountered any new cases of IPA at the time of writing.
T68 8296-8306 Sentence denotes Conclusion
T69 8307-8460 Sentence denotes Using this case series, we would like to raise awareness about COVID-19-associated pulmonary aspergillosis, in view of its potential detrimental outcome.
T70 8461-8711 Sentence denotes We believe that a low threshold for screening, prophylaxis and early antifungal treatment is of paramount importance, especially since different immunosuppressive therapies have been suggested to treat patients suffering from this alarming condition.
T71 8713-8726 Sentence denotes Abbreviations
T72 8727-8760 Sentence denotes COVID-19 Coronavirus disease 2019
T73 8761-8825 Sentence denotes SARS-COV-2 virus Severe acute respiratory syndrome coronavirus 2
T74 8826-8849 Sentence denotes ICU Intensive care unit
T75 8850-8886 Sentence denotes IPA Invasive pulmonary aspergillosis
T76 8887-8925 Sentence denotes IAA Influenza-associated aspergillosis
T77 8926-8966 Sentence denotes ARDS Acute respiratory distress syndrome
T78 8967-8973 Sentence denotes h Hour
T79 8974-9001 Sentence denotes BAL Broncho-alveolar lavage
T80 9002-9024 Sentence denotes CT Computed tomography
T81 9025-9089 Sentence denotes EORTC European Organization for Research and Treatment of Cancer
T82 9090-9130 Sentence denotes AspICU Aspergillosis intensive care unit
T83 9131-9140 Sentence denotes No Number
T84 9141-9162 Sentence denotes SD Standard deviation
T85 9163-9207 Sentence denotes HEPA High-efficiency particulate air filters
T86 9208-9224 Sentence denotes Publisher's Note
T87 9225-9343 Sentence denotes Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
T88 9345-9361 Sentence denotes Acknowledgements
T89 9362-9462 Sentence denotes We want to thank our entire ICU team for their unwavering commitment during these challenging times.
T90 9464-9486 Sentence denotes Authors’ contributions
T91 9487-9567 Sentence denotes LR wrote the first draft of manuscript with input and revisions from NVR and NS.
T92 9568-9616 Sentence denotes NS collected the data from the source documents.
T93 9617-9660 Sentence denotes TVH and LR performed the literature search.
T94 9661-9798 Sentence denotes PB and HD advised on the reporting of the clinical data; RN and HM on the reporting of the microbiological and infection prevention data.
T95 9799-9846 Sentence denotes All authors had full access to all of the data.
T96 9847-9898 Sentence denotes All authors read and approved the final manuscript.
T97 9900-9907 Sentence denotes Funding
T98 9908-9913 Sentence denotes None.
T99 9915-9949 Sentence denotes Availability of data and materials
T100 9950-10075 Sentence denotes The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
T101 10077-10119 Sentence denotes Ethics approval and consent to participate
T102 10120-10173 Sentence denotes Publication approval granted by the Ethics Committee.
T103 10175-10198 Sentence denotes Consent for publication
T104 10199-10214 Sentence denotes Not applicable.
T105 10216-10235 Sentence denotes Competing interests
T106 10236-10294 Sentence denotes The authors declare that they have no competing interests.