> top > projects > LitCovid-sentences > docs > PMC:7646269 > annotations
LitCovid-sentences  

PMC:7646269 JSONTXT 16 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-83 Sentence denotes Putative invasive pulmonary aspergillosis in critically ill patients with COVID‐19:
T2 84-125 Sentence denotes An observational study from New York City
T3 126-139 Sentence denotes MITAKA et al.
T4 141-149 Sentence denotes Abstract
T5 150-158 Sentence denotes Abstract
T6 160-170 Sentence denotes Background
T7 171-332 Sentence denotes Critically ill patients with coronavirus disease‐2019 (COVID‐19) are at the theoretical risk of invasive pulmonary aspergillosis (IPA) due to known risk factors.
T8 334-350 Sentence denotes Patients/Methods
T9 351-477 Sentence denotes We aimed to describe the clinical features of COVID‐19‐associated pulmonary aspergillosis at a single centre in New York City.
T10 478-602 Sentence denotes We performed a retrospective chart review of all patients with COVID‐19 with Aspergillus isolated from respiratory cultures.
T11 604-611 Sentence denotes Results
T12 612-797 Sentence denotes A total of seven patients with COVID‐19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified, all of whom were mechanically ventilated in the ICU.
T13 798-844 Sentence denotes Four patients were classified as putative IPA.
T14 845-901 Sentence denotes The median age was 79 years, and all patients were male.
T15 902-978 Sentence denotes The patients had been mechanically ventilated for a mean of 6.8 days (range:
T16 979-1019 Sentence denotes 1‐14 days) before Aspergillus isolation.
T17 1020-1080 Sentence denotes Serum galactomannan level was positive for only one patient.
T18 1081-1201 Sentence denotes The majority of our cases received much higher doses of glucocorticoids than the dosage with a proven mortality benefit.
T19 1202-1225 Sentence denotes All four patients died.
T20 1227-1238 Sentence denotes Conclusions
T21 1239-1364 Sentence denotes Vigilance for secondary fungal infections will be needed to reduce adverse outcomes in critically ill patients with COVID‐19.
T22 1366-1381 Sentence denotes 1 INTRODUCTION
T23 1382-1477 Sentence denotes Invasive pulmonary aspergillosis (IPA) has been reported in critically ill patients in the ICU.
T24 1478-1666 Sentence denotes 1 , 2 Patients with coronavirus disease‐2019 (COVID‐19) may develop acute hypoxemic respiratory failure and are at high risk of requiring mechanical ventilation with prolonged ICU stays.
T25 1667-1752 Sentence denotes Further, patients with severe COVID‐19 may be administered high‐dose glucocorticoids.
T26 1753-1856 Sentence denotes Hence, there is a theoretical risk of IPA in patients with COVID‐19 due to combined known risk factors.
T27 1857-1930 Sentence denotes However, there are scant data on aspergillosis in patients with COVID‐19.
T28 1931-2110 Sentence denotes 3 , 4 , 5 , 6 The aim of the study was to describe the clinical features of critically ill COVID‐19‐infected patients with pulmonary aspergillosis at a New York City hospital.
T29 2112-2135 Sentence denotes 2 PATIENTS AND METHODS
T30 2136-2363 Sentence denotes We performed a retrospective chart review of all COVID‐19‐infected patients with Aspergillus isolates in respiratory samples during 21 March and 22 April 2020 at Mount Sinai Beth Israel, an acute care hospital in New York City.
T31 2364-2525 Sentence denotes We collected longitudinal clinical data, including fraction of inspired oxygen (FiO2) and vital signs, laboratory and microbiology data, treatment, and outcomes.
T32 2526-2600 Sentence denotes Serial chest radiographs and computed tomography (CT) scans were reviewed.
T33 2601-2673 Sentence denotes Glucocorticoid dose was converted into an equivalent dose of prednisone.
T34 2674-2730 Sentence denotes Fever was defined as a temperature of ≥100.4 Fahrenheit.
T35 2731-2873 Sentence denotes We used the clinical algorithm for ICU patients to classify pulmonary aspergillosis as either putative IPA or colonisation (AspICU algorithm).
T36 2874-3075 Sentence denotes 7 As per the clinical algorithm, persistent fever was defined as fever persisting despite at least 3 days of antibiotic therapy or recrudescent fever while on antibiotics without other apparent cause.
T37 3076-3251 Sentence denotes Worsening respiratory status was defined by an increase in FiO2 requirement on mechanical ventilation, or worsening respiratory failure led to invasive mechanical ventilation.
T38 3252-3363 Sentence denotes Study approval was obtained from the institutional review board of the Icahn School of Medicine at Mount Sinai.
T39 3365-3375 Sentence denotes 3 RESULTS
T40 3376-3508 Sentence denotes A total of seven patients with COVID‐19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified.
T41 3509-3593 Sentence denotes According to the AspICU algorithm, 7 four patients were classified as putative IPA.
T42 3594-3891 Sentence denotes None of the patients had European Organization for Research and Treatment of Cancer/ Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) host factors, including neutropenia and prolonged use of corticosteroids.
T43 3892-3994 Sentence denotes Only one patient had a pre‐existing lung disease (chronic obstructive pulmonary disease in Patient 1).
T44 3995-4309 Sentence denotes All four patients had compatible signs (fever refractory to at least 3 days of appropriate therapy or worsening respiratory insufficiency despite appropriate antibiotic therapy and ventilatory support), host factor (glucocorticoid treatment with prednisone equivalent > 20 mg/d) and abnormal radiographic findings.
T45 4310-4524 Sentence denotes Radiographic abnormalities included worsening infiltrates (Patient 1), opacities with dense consolidations (Patient 2), cavitary pneumonia (Patient 3) and diffuse interstitial and patchy hazy opacities (Patient 4).
T46 4525-4634 Sentence denotes The remaining three patients were classified as having colonisation as they lacked compatible clinical signs.
T47 4635-4725 Sentence denotes For those three patients, subsequent clinical deterioration was explained by other causes.
T48 4726-4806 Sentence denotes Clinical characteristics of the patients with putative IPA are shown in Table 1.
T49 4807-4835 Sentence denotes The median age was 79 years.
T50 4836-4970 Sentence denotes All experienced worsening respiratory status leading to invasive mechanical ventilation before the isolation of Aspergillus fumigatus.
T51 4971-5047 Sentence denotes The patients had been mechanically ventilated for a mean of 6.8 days (range:
T52 5048-5088 Sentence denotes 1‐14 days) before Aspergillus isolation.
T53 5089-5194 Sentence denotes At Aspergillus isolation, fever and leukocytosis were present in one and all four patients, respectively.
T54 5195-5267 Sentence denotes Serum galactomannan level was positive for only one patient (Patient 2).
T55 5268-5336 Sentence denotes All patients received concomitant broad‐spectrum antibiotic therapy.
T56 5337-5462 Sentence denotes Table 1 Clinical characteristics of critically ill COVID‐19‐infected patients with putative invasive pulmonary aspergillosis
T57 5463-5505 Sentence denotes Patient 1 Patient 2 Patient 3 Patient 4
T58 5506-5529 Sentence denotes Age (y) 82 79 77 77
T59 5530-5560 Sentence denotes Gender Male Male Male Male
T60 5561-5580 Sentence denotes Comorbid conditions
T61 5581-5610 Sentence denotes Hypertension No Yes No No
T62 5611-5636 Sentence denotes Diabetes No No No Yes
T63 5637-5677 Sentence denotes Coronary artery disease No Yes No No
T64 5678-5732 Sentence denotes Chronic obstructive pulmonary disease Yes No No No
T65 5733-5785 Sentence denotes History of cerebrovascular accident No Yes No No
T66 5786-5821 Sentence denotes History of cancer Yes Yes No No
T67 5822-5846 Sentence denotes Dementia No No No No
T68 5847-5971 Sentence denotes Timing of positive culture for Aspergillus fumigatus (hospital day) Day 15 and 20 Day 7, 10, and 16 Day 10 and 14 Day 10
T69 5972-6014 Sentence denotes Clinical features at Aspergillus isolation
T70 6015-6037 Sentence denotes Fever No No Yes No
T71 6038-6101 Sentence denotes Respiratory status at Aspergillus isolation IMV IMV IMV IMV
T72 6102-6281 Sentence denotes New radiographic abnormalities on chest CT or X‐ray Worsening infiltrates Opacities with dense consolidations Cavitary pneumonia Diffuse interstitial and patchy hazy opacities
T73 6282-6337 Sentence denotes White blood cell count (103/μL) 32.9 21.1 20.1 20.2
T74 6338-6381 Sentence denotes Platelet count (103/μL) 376 146 420 123
T75 6382-6427 Sentence denotes Procalcitonin (ng/mL) 0.16 0.30 3.30 9.34
T76 6428-6468 Sentence denotes Lactic acid (mmol/L) 1.0 3.6 1.6 3.7
T77 6469-6512 Sentence denotes Total bilirubin (mg/dL) 2.4 1.1 1.4 2.9
T78 6513-6557 Sentence denotes Serum creatinine (mg/dL) 2.6 3.1 1.5 4.1
T79 6558-6607 Sentence denotes Serum galactomannan NA 0.71 Negative Negative
T80 6608-6647 Sentence denotes Vasopressor support Yes Yes Yes Yes
T81 6648-6669 Sentence denotes Inpatient medications
T82 6670-6685 Sentence denotes Glucocorticoids
T83 6686-6751 Sentence denotes Cumulative dose in prednisone equivalent (mg) 932 1000 870 87
T84 6752-6809 Sentence denotes Starting date (hospital day) Day 8 Day 2 Day 2 Day 10
T85 6810-6837 Sentence denotes Duration (d) 10 10 12 3
T86 6838-6866 Sentence denotes Tocilizumab No Yes No No
T87 6867-6971 Sentence denotes Antibiotics Cefepime + Vancomycin Cefepime + Vancomycin Meropenem + Vancomycin Cefepime + Vancomycin
T88 6972-7045 Sentence denotes Antifungal therapy Voriconazole Voriconazole Voriconazole Caspofungin
T89 7046-7117 Sentence denotes Abbreviations: IMV, invasive mechanical ventilation; NA, not available.
T90 7118-7265 Sentence denotes John Wiley & Sons, Ltd This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response.
T91 7266-7448 Sentence denotes It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.
T92 7449-7585 Sentence denotes All four patients concomitantly received glucocorticoids, with three of which were already given steroids for a mean of 6.6 days (range:
T93 7586-7632 Sentence denotes 5‐8 days) before the isolation of Aspergillus.
T94 7633-7741 Sentence denotes In the remaining one patient (patients 4), glucocorticoid therapy was administered at Aspergillus isolation.
T95 7742-7815 Sentence denotes The overall mean duration of glucocorticoid exposure was 8.5 days (range:
T96 7816-7894 Sentence denotes 3‐11 days) with a mean cumulative prednisone equivalent dose of 722 mg (range:
T97 7895-7907 Sentence denotes 87‐1000 mg).
T98 7908-7981 Sentence denotes One patient received tocilizumab after Aspergillus isolation (Patient 3).
T99 7982-8173 Sentence denotes Patient 1 was an 82‐year‐old man with a history of COPD and pharyngeal cancer who was transferred to the ICU on hospital day 3 for acute respiratory distress syndrome (ARDS) and septic shock.
T100 8174-8307 Sentence denotes He was afebrile at Aspergillus isolation on hospital day 15, but respiratory status deteriorated with increased FiO2 from 50% to 80%.
T101 8308-8366 Sentence denotes A chest radiograph showed worsening bilateral infiltrates.
T102 8367-8421 Sentence denotes He was initially treated with cefepime and vancomycin.
T103 8422-8501 Sentence denotes Voriconazole was added 3 days after the first positive culture for Aspergillus.
T104 8502-8572 Sentence denotes Leukocytosis persisted on broad‐spectrum antibiotics and voriconazole.
T105 8573-8682 Sentence denotes He developed intermittent fever with worsening respiratory status and required continued vasopressor support.
T106 8683-8820 Sentence denotes The family subsequently requested no further aggressive treatment, and he passed away 17 days after the initiation of antifungal therapy.
T107 8821-9110 Sentence denotes Patient 2 was a 79‐year‐old man with a history of hypertension, coronary artery disease, transient ischaemic attack, and renal cell carcinoma who was transferred to the ICU on hospital day 6 for worsening acute hypoxemic respiratory failure requiring intubation and mechanical ventilation.
T108 9111-9232 Sentence denotes He was afebrile and had been on non‐invasive ventilation (NIV) for 6 days before Aspergillus isolation on hospital day 7.
T109 9233-9306 Sentence denotes Respiratory culture grew Aspergillus fumigatus and Staphylococcus aureus.
T110 9307-9443 Sentence denotes A chest CT showed dense bilateral lower lobe consolidations, multifocal ground‐glass opacities, pneumomediastinum and pneumopericardium.
T111 9444-9498 Sentence denotes He was initially treated with cefepime and vancomycin.
T112 9499-9571 Sentence denotes Voriconazole was started at the second positive culture for Aspergillus.
T113 9572-9661 Sentence denotes A repeat chest CT showed similar findings together with worsening ground‐glass opacities.
T114 9662-9852 Sentence denotes Despite subsequent treatment with meropenem, vancomycin, and voriconazole, he continued to deteriorate with persistent leukocytosis, worsening respiratory status, and multiorgan dysfunction.
T115 9853-9915 Sentence denotes He expired 13 days after the initiation of antifungal therapy.
T116 9916-10066 Sentence denotes Patient 3 was a 77‐year‐old man with no past medical history who was admitted to the ICU for acute hypoxemic respiratory failure requiring intubation.
T117 10067-10132 Sentence denotes He developed a fever at Aspergillus isolation on hospital day 10.
T118 10133-10172 Sentence denotes Respiratory status had remained stable.
T119 10173-10228 Sentence denotes He was initially treated with meropenem and vancomycin.
T120 10229-10284 Sentence denotes Fever persisted for 4 days, and voriconazole was added.
T121 10285-10554 Sentence denotes A chest CT showed bilateral patchy ground‐glass opacities, bilateral mid to lower lung zone predominant consolidative opacities, bilateral lower lobe cavitary lesions, the largest of which is seen within the right lung base and one of which contains an air‐fluid level.
T122 10555-10598 Sentence denotes He was then treated with voriconazole only.
T123 10599-10645 Sentence denotes Fever and leukocytosis subsided within 6 days.
T124 10646-10887 Sentence denotes A repeat chest CT after 2 weeks of voriconazole showed improved bilateral ground‐glass opacities, stable to mildly improved cavitary pneumonia within the bilateral lower lobes, and a new cavitary lesion within the subpleural left lower lobe.
T125 10888-11053 Sentence denotes The subsequent course was complicated by intravenous catheter‐related thrombophlebitis with Staphylococcus epidermidis bacteremia, which was treated with vancomycin.
T126 11054-11246 Sentence denotes He had a protracted hospital course with persistent metabolic encephalopathy, chronic respiratory failure required tracheostomy, multiorgan dysfunction and subsequent Staphylococcus pneumonia.
T127 11247-11363 Sentence denotes Due to a lack of improvement, the family requested comfort care, and he expired after 1 month of antifungal therapy.
T128 11364-11538 Sentence denotes Patient 4 was a 77‐year‐old man with a history of type 2 diabetes mellitus who was transferred to the ICU on hospital day 8 for worsening acute hypoxemic respiratory failure.
T129 11539-11733 Sentence denotes He had been on NIV for 8 days and on cefepime and vancomycin until respiratory status further deteriorated, which required intubation and transfer to the ICU 2 days before Aspergillus isolation.
T130 11734-11794 Sentence denotes He was afebrile at Aspergillus isolation on hospital day 10.
T131 11795-11851 Sentence denotes Chest radiographs showed diffuse ground‐glass opacities.
T132 11852-11915 Sentence denotes Caspofungin was started together with meropenem and vancomycin.
T133 11916-12019 Sentence denotes He continued to deteriorate with multiorgan dysfunction and expired after 3 days of antifungal therapy.
T134 12021-12034 Sentence denotes 4 DISCUSSION
T135 12035-12144 Sentence denotes Reports of pulmonary aspergillosis complicating severe COVID‐19 required mechanical ventilation are emerging.
T136 12145-12273 Sentence denotes 5 , 6 Most patients did not have underlying immunocompromising conditions, as observed in patients with ARDS due to influenza.
T137 12274-12470 Sentence denotes 2 Detailed data from patients who presented in the first waves of COVID‐19 pandemic are needed to define the incidence and clinical features of COVID‐19‐associated pulmonary aspergillosis (CAPA).
T138 12471-12591 Sentence denotes 8 We herein describe the clinical characteristics of four cases of critically ill COVID‐19 complicated by putative IPA.
T139 12592-12693 Sentence denotes Early diagnosis of IPA is critical but challenging in mechanically ventilated patients with COVID‐19.
T140 12694-12816 Sentence denotes Bronchoscopy and transbronchial biopsy are rarely performed given the risk of complications and transmission of the virus.
T141 12817-12899 Sentence denotes Further, pneumonia due to SARS‐CoV‐2 may obscure the radiological findings of IPA.
T142 12900-13087 Sentence denotes Consolidation is commonly seen in both COVID‐19 and superimposing pulmonary aspergillosis, and any new radiological signs could be obscured by background bilateral ground‐glass opacities.
T143 13088-13234 Sentence denotes Systemic inflammatory markers are almost always elevated with severe COVID‐19, which make them less useful to diagnose secondary fungal infection.
T144 13235-13492 Sentence denotes While it has been suggested that a low procalcitonin level may indicate a high likelihood for invasive fungal infection in critically ill patients with clinical signs of sepsis, 9 the procalcitonin level was elevated in only two patients with putative IPA.
T145 13493-13749 Sentence denotes At our institution, fungal cultures are routinely performed on bronchoscopy specimens and other respiratory specimens as clinically indicated; consequently, it is plausible there were instances of Aspergillus respiratory infection that were not identified.
T146 13750-13817 Sentence denotes Aspergillus infection can be seen in construction‐related clusters.
T147 13818-13989 Sentence denotes 10 While there was some construction at our institution during the first wave of COVID‐19, it was physically remote from the units where all of the cases were identified.
T148 13990-14134 Sentence denotes Further, there were no instances of isolating Aspergillus from any patients without the diagnosis of COVID‐19 within or around the study period.
T149 14135-14267 Sentence denotes For research purposes, EORTC/MSG Consensus Group have proposed definitions of proven, probable and possible invasive fungal disease.
T150 14268-14462 Sentence denotes 11 However, these consensus definitions are much less useful for immunocompetent patients in the ICU, as the diagnosis of probable or possible IPA requires the presence of classic host factors.
T151 14463-14660 Sentence denotes We used the AspICU criteria, which is an algorithm for diagnosing IPA in the ICU patients with positive Aspergillus endotracheal aspirate cultures, 7 to distinguish putative IPA from colonisation.
T152 14661-14804 Sentence denotes However, the performance characteristics of the algorithm for COVID‐19 patients have not been validated with autopsy or postmortem biopsy data.
T153 14805-14877 Sentence denotes Serum galactomannan was positive in only one patient in our case series.
T154 14878-15014 Sentence denotes Serum galactomannan is more specific for invasive aspergillosis than beta‐D‐glucan but has poor sensitivity in non‐neutropenic patients.
T155 15015-15131 Sentence denotes 12 Combining three case series of CAPA, only three (13%) out of 23 patients had positive serum galactomannan level.
T156 15132-15337 Sentence denotes 5 , 6 , 13 The less frequently elevated serum galactomannan levels might simply reflect colonisation rather than infection or suggest that angioinvasive pulmonary infection is a rare phenomenon in CAPA.
T157 15338-15425 Sentence denotes In any case, the diagnostic value of serum galactomannan for CAPA seems less promising.
T158 15426-15560 Sentence denotes All the patients with putative IPA died in our consecutive cases, suggesting the grave prognosis of critically ill patients with CAPA.
T159 15561-15740 Sentence denotes On the other hand, Alanio et al reported no significant difference in mortality between IPA and non‐IPA patients in a report of eight COVID‐19‐infected patients with putative IPA.
T160 15741-15866 Sentence denotes 6 Further data from multi‐institutional series are needed to clearly characterise the potential impact on mortality of CAPA.
T161 15867-16097 Sentence denotes Although dexamethasone was recently shown to decrease 28‐day mortality in mechanically ventilated patients with COVID‐19, 14 the majority of our cases received much higher doses of glucocorticoids than what was proven beneficial.
T162 16098-16281 Sentence denotes Since one of the potential sequelae of COVID‐19 is secondary fungal infections as our cases demonstrated, vigilance for secondary infections will be needed to reduce adverse outcomes.
T163 16282-16578 Sentence denotes Clinicians should have a high index of suspicion for CAPA when a critically ill patient with COVID‐19 in the ICU develops further respiratory decompensation, fevers or new or worsening radiographic abnormalities of the lungs, particularly if there is no response to empiric antibacterial therapy.
T164 16579-16759 Sentence denotes It is important to obtain a respiratory culture for fungal pathogens and a serum galactomannan level in these settings to attempt to identify this ominous complication of COVID‐19.
T165 16761-16782 Sentence denotes CONFLICTS OF INTEREST
T166 16783-16829 Sentence denotes There are no conflicts of interest to declare.
T167 16831-16851 Sentence denotes AUTHOR CONTRIBUTIONS
T168 16852-16866 Sentence denotes Hayato Mitaka:
T169 16867-17031 Sentence denotes Conceptualization (equal); data curation (equal); formal analysis (equal); investigation (equal); writing‐original draft (lead); writing‐review and editing (equal).
T170 17032-17040 Sentence denotes David C.
T171 17041-17049 Sentence denotes Perlman:
T172 17050-17154 Sentence denotes Conceptualization (equal); methodology (equal); supervision (equal); writing‐review and editing (equal).
T173 17155-17169 Sentence denotes Waleed Javaid:
T174 17170-17231 Sentence denotes Supervision (equal); writing‐review and editing (supporting).
T175 17232-17246 Sentence denotes Nadim Salomon:
T176 17247-17434 Sentence denotes Conceptualization (equal); data curation (equal); investigation (equal); methodology (equal); supervision (equal); writing‐original draft (supporting); writing‐review and editing (equal).
T177 17436-17463 Sentence denotes DATA AVAILABILITY STATEMENT
T178 17464-17581 Sentence denotes The data that support the findings of this study are available from the corresponding author upon reasonable request.
T179 17582-17657 Sentence denotes The data are not publicly available due to privacy or ethical restrictions.