LitCovid-sentences  

PMC:7344504 / 821-14430 JSONTXT 12 Projects

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Id Subject Object Predicate Lexical cue
T9 0-2 Sentence denotes 1.
T10 3-15 Sentence denotes Introduction
T11 16-207 Sentence denotes There have been suggestions that coronavirus disease 2019 (COVID-19) might increase the risk of superinfections [1] and, particularly, invasive pulmonary aspergillosis (IPA) co-infection [2].
T12 208-383 Sentence denotes COVID-19-associated pulmonary aspergillosis (CAPA) is a recently described disease entity affecting patients in intensive care unit (ICUs) with severe pulmonary abnormalities.
T13 384-570 Sentence denotes Small cohorts of 31 patients in the Netherlands [3], 27 patients in France [4] and 19 patients in Germany [5] have been published, showing CAPA rates of 19.4%, 33% and 26%, respectively.
T14 571-638 Sentence denotes An additional two fatal cases of CAPA were recently reported [6,7].
T15 639-894 Sentence denotes The numbers resemble what has been observed in influenza, where influenza in ICU patients has been identified as an independent risk factor for invasive pulmonary aspergillosis and which is associated with an even higher mortality rate than IPA alone [8].
T16 895-1083 Sentence denotes In addition, in the Netherlands, an estimated 11.3% of cases with invasive aspergillosis are infected with an azole-resistant isolate [9], potentially increasing mortality to 50–100% [10].
T17 1084-1220 Sentence denotes We present the first case of azole-resistant Aspergillus fumigatus in a SARS-CoV-2-positive immunocompetent patient admitted to the ICU.
T18 1222-1224 Sentence denotes 2.
T19 1225-1248 Sentence denotes Case Report and Results
T20 1249-1346 Sentence denotes A 74-year-old patient was admitted because of respiratory insufficiency amid the COVID-19 crisis.
T21 1347-1439 Sentence denotes Eleven days prior to admission, she had been suffering from fever (38.5 °C) and a dry cough.
T22 1440-1495 Sentence denotes Three days after symptom onset, she developed diarrhea.
T23 1496-1720 Sentence denotes Her medical history included complaints of reflux and pain due to arthrosis of the hip and knees, for which she uses a proton-pump inhibitor and a nonsteroidal anti-inflammatory drug pantoprazol and etoricoxib, respectively.
T24 1721-1788 Sentence denotes She stopped smoking 20 years ago and was healthy and fit otherwise.
T25 1789-1837 Sentence denotes Patient characteristics can be found in Table 1.
T26 1838-2121 Sentence denotes This study, “Clinical course and prognostic factors for COVID-19” with project identification code CWZ-nr 027-2020, was approved in March 20202 by the Canisius Wilhelmina Hospital medical ethics committee and patient informed consent was acquired antemortem with opt out possibility.
T27 2122-2224 Sentence denotes At presentation to the emergency department, she had been feeling progressively dyspneic for two days.
T28 2225-2361 Sentence denotes On physical examination, her oxygenation was 82%, with 28 breaths per minute in room air, pulmonary wheezing and an extended expiration.
T29 2362-2457 Sentence denotes Oxygenation improved to 94% with 5 L O2 via a nasal cannula, but she desaturated during speech.
T30 2458-2511 Sentence denotes Her BMI was 27.7 (80 kg) and her temperature 37.8 °C.
T31 2512-2577 Sentence denotes No other aberrant observations on physical examination were made.
T32 2578-2631 Sentence denotes Her Glasgow Coma Scale was 15 and her ECG was normal.
T33 2632-3061 Sentence denotes Her C-reactive protein (CRP) was 214 mg/L, and other laboratory findings included slightly elevated leucocytes (12.6 × 109 /L) and neutrophils (8.4 × 109 /L), elevated liver enzymes (alkaline phosphatase 528 U/L; GGT 376 U/L; AST 76 U/L; LD 745 U/L), slightly elevated pro-calcitonin (0.25 µg/L; <0.5 µg/L not suggestive of bacterial infection), increased ferritin (1442 µg/L), and normal electrolyte, glucose and renal function.
T34 3062-3116 Sentence denotes SARS-CoV-2 nasopharyngeal and throat swabs were taken.
T35 3117-3342 Sentence denotes A low-dose chest CT demonstrated extensive centralized and peripheral bilateral ground glass opacities with left-sided consolidations and bilateral fibrotic bands without pleural effusions and vascular enlargement (Figure 1).
T36 3343-3411 Sentence denotes The CO-RADS score was 5 and CT-severity score was 24 out of 25 [11].
T37 3412-3593 Sentence denotes Because of the high probability of SARS-CoV-2 infection, chloroquine treatment was started (600 mg and 300 mg on day 1, 300 mg q12h days 2–5), which was national policy at the time.
T38 3594-3675 Sentence denotes The SARS-CoV-2 PCR of a nasopharyngeal swab was positive (Ct 30.59; E gene [12]).
T39 3676-3768 Sentence denotes Blood cultures remained negative, as were nasopharynx bacterial cultures taken at admission.
T40 3769-3849 Sentence denotes The patient was subsequently admitted to our general inpatient respiratory ward.
T41 3850-3909 Sentence denotes An overview of her hospital course is depicted in Figure 2.
T42 3910-4008 Sentence denotes The CRP remained highly stable over the following days at around 200 mg/L with a range of 192–214.
T43 4009-4088 Sentence denotes However, the patient needed increasing oxygenation with a non-rebreathing mask.
T44 4089-4182 Sentence denotes Empirical treatment of a suspected bacterial superinfection was started with ceftriaxone i.v.
T45 4183-4196 Sentence denotes 2000 mg q24h.
T46 4197-4397 Sentence denotes Five days after admission, the maximum (15 L O2) oxygenation with the non-rebreathing mask became insufficient and the patient was admitted to the ICU for respiratory support and intensive monitoring.
T47 4398-4541 Sentence denotes In the ICU, HFNO (high-flow nasal oxygen therapy) and selective digestive decontamination (SDD) were initiated, which includes ceftriaxone i.v.
T48 4542-4659 Sentence denotes 2000 mg q24h for 4 days and a combined oral non-absorbable suspension of amphotericin B, colistin and tobramycin q6h.
T49 4660-4731 Sentence denotes In this patient, ceftriaxone was continued de facto for another 4 days.
T50 4732-4892 Sentence denotes Routine bacterial and fungal (peri-anal, throat and tracheal aspirate) surveillance cultures were done twice weekly in adherence with our local SDD policy [13].
T51 4893-5023 Sentence denotes Within a few hours after admission to the ICU, her blood oxygenation became insufficient with HFNO at FiO2 100% and 60 L/min flow.
T52 5024-5097 Sentence denotes Therefore, she was sedated, intubated and put on a mechanical ventilator.
T53 5098-5200 Sentence denotes A CT angiography of the chest was performed which demonstrated significant bilateral pulmonary emboli.
T54 5201-5283 Sentence denotes Anticoagulants (enoxaparine anti-factor Xa) were initiated in therapeutic dosages.
T55 5284-5361 Sentence denotes Pressure control ventilation was required with the patient in prone position.
T56 5362-5513 Sentence denotes Because of the need for increasing noradrenaline dosages during circulatory shock, hydrocortisone 100 mg q8h was initiated and continued for five days.
T57 5514-5595 Sentence denotes Cardiac ultrasound showed a minor tricuspid insufficiency but no major pathology.
T58 5596-5707 Sentence denotes Aspergillus fumigatus was recovered from high-volume tracheal aspirate cultures [14] obtained at ICU admission.
T59 5708-6028 Sentence denotes Aspergillus galactomannan (Platelia Aspergillus; Bio-Rad, Marnes-La-Coquette, France) ratio at this time was >3.0 (positive) in a tracheal aspirate and β-d-glucan (Fungitell assay; Associates of Cape Cod Inc., East Falmouth, MA, USA) in serum was 1590 pg/mL (positive), after which a putative diagnosis of CAPA was made.
T60 6029-6102 Sentence denotes Serum galactomannan remained negative (<0.5) in three subsequent samples.
T61 6103-6120 Sentence denotes Voriconazole i.v.
T62 6121-6177 Sentence denotes 6 mg/kg q12h was started in addition to caspofungin i.v.
T63 6178-6302 Sentence denotes 70 mg q24h until the VIPcheck (Mediaproducts BV, Groningen, The Netherlands), used to detect azole resistance, was negative.
T64 6303-6552 Sentence denotes MICs determined with broth microdilution using CLSI methodology of the A. fumigatus isolate were as follows: amphotericin B 0.5 mg/L, micafungin and anidulafungin <0.016 mg/L, itraconazole 1 mg/L, voriconazole 0.25 mg/L, and posaconazole 0.063 mg/L.
T65 6553-6653 Sentence denotes Voriconazole was switched to oral administration of 200 mg q12h with discontinuation of caspofungin.
T66 6654-6734 Sentence denotes During SDD, bacterial cultures remained negative throughout her stay in the ICU.
T67 6735-6882 Sentence denotes On day 6 after admission (day 2 at the ICU), continuous venovenous hemofiltration was initiated because of rapidly progressive acute renal failure.
T68 6883-7143 Sentence denotes A. fumigatus was persistently cultured from tracheal aspirate samples during voriconazole treatment and β-d-glucan levels remained positive with 1149 and 1458 pg/µl, at 1 and 6 days (day 8 and 13 after hospital admission) of voriconazole therapy, respectively.
T69 7144-7331 Sentence denotes Voriconazole serum therapeutic drug monitoring was performed as recommended [15], with therapeutic concentrations of 4.72 mg/L, 2.78 mg/L and 1.43 mg/L at day 13, 15 and 17, respectively.
T70 7332-7436 Sentence denotes The respiratory situation improved marginally in the subsequent 7 days but declined steadily thereafter.
T71 7437-7603 Sentence denotes Pressure support and pressure control ventilation were alternated between days 12 and 19 and attempts to return the patient to a supine position failed several times.
T72 7604-7740 Sentence denotes After 7 days, A. fumigatus grew on the itraconazole and voriconazole wells of the second VIPcheck on day 19 (tracheal aspirate culture).
T73 7741-7927 Sentence denotes MICs of this A. fumigatus isolate were as follows: amphotericin B 0.5 mg/L, anidulafungin and micafungin <0.016 mg/L, itraconazole 16 mg/L, voriconazole 2 mg/L and posaconazole 0.5 mg/L.
T74 7928-8003 Sentence denotes Voriconazole treatment was changed to liposomal amphotericin B 200 mg q24h.
T75 8004-8126 Sentence denotes Subsequent cyp51A gene sequencing identified a TR34/L98H mutation, probably responsible for the observed azole resistance.
T76 8127-8275 Sentence denotes On day 22, ventilation and oxygenation of the patient deteriorated further without further treatment options and therapy was discontinued on day 23.
T77 8276-8305 Sentence denotes An autopsy was not performed.
T78 8307-8309 Sentence denotes 3.
T79 8310-8320 Sentence denotes Discussion
T80 8321-8476 Sentence denotes We report the first case of azole-resistant CAPA, which occurred in an immunocompetent host during ICU support without a previous history of azole therapy.
T81 8477-8769 Sentence denotes The A. fumigatus cyp51A gene TR34/L98H mutation found in this patient has been well described as an environmentally acquired mutation [16], which is in line with data from clinical studies where two-thirds of patients with azole-resistant infections had no history of azole pretreatment [10].
T82 8770-8987 Sentence denotes This case underscores the importance of early diagnosis and the need for resistance surveillance, comparable to what has been described in influenza patients [9,17], given the emergence of triazole resistance [18,19].
T83 8988-9256 Sentence denotes The sensitivity for detection of resistance in primary cultures with the VIPcheck plate depends on the number of A. fumigatus colonies that are tested, as clinical cultures may contain both mixed azole-susceptible and azole-resistant isolates during an infection [20].
T84 9257-9454 Sentence denotes We suspect that A. fumigatus isolated in the first tracheal aspirate was already a mixed culture but was missed in initial fungal cultures due to abundance of azole-susceptible A. fumigatus spores.
T85 9455-9603 Sentence denotes Molecular detection could have given a suggestion to the presence of a mixed culture [21] but PCR could not be performed due to absence of material.
T86 9604-9790 Sentence denotes The TR34/L98H had a phenotype with high itraconazole MIC (>16 mg/L) and low voriconazole MIC (2 mg/L), similar to strains which have been described only recently in the Netherlands [22].
T87 9791-9871 Sentence denotes IPA is known to be problematic to diagnose in the non-neutropenic ICU host [23].
T88 9872-10148 Sentence denotes Regardless of the compelling evidence for CAPA in this patient, the EORTC/MSGERC [24] host criteria for invasive fungal disease were not met, nor did the patient meet the AspICU algorithm because we tested tracheal aspirates instead of bronchoalveolar lavage (BAL) fluid [25].
T89 10149-10279 Sentence denotes This is in line with findings from other groups, where CAPA patients did not meet the EORTC/MSGERC host criteria either [3,4,5,6].
T90 10280-10512 Sentence denotes In addition, the American Association for Bronchology and Interventional Pulmonology (AABIP) has issued a statement advising against routine bronchoscopy in COVID-19 patients, as it poses substantial risk to patients and staff [26].
T91 10513-10662 Sentence denotes BAL should only be considered in intubated patients if upper respiratory samples are negative and BAL would significantly change clinical management.
T92 10663-10803 Sentence denotes Tracheal aspirate cultures, as performed twice weekly in our patient, repeatedly identified A. fumigatus as the only micro-organism present.
T93 10804-10951 Sentence denotes In the first positive culture, five colonies were tested for resistance with the VIPcheck plate as is recommended to exclude azole resistance [15].
T94 10952-11222 Sentence denotes When surveillance cultures of tracheal aspirates were persistently cultured positive with A. fumigatus during voriconazole therapy, we suspected the selection of resistant isolates which were probably already present in the first samples, albeit in undetectable numbers.
T95 11223-11262 Sentence denotes An autopsy to confirm IPA was not done.
T96 11263-11430 Sentence denotes Serum galactomannan testing has been shown to be a fairly sensitive diagnostic tool (70%) in neutropenic patients with pathology-proven invasive aspergillosis [27,28].
T97 11431-11686 Sentence denotes However, in patients who are non-neutropenic, serum galactomannan sensitivity of around 25% has been reported [27], which may explain the low number of serum galactomannan positive findings in recently published case reports [6,7] and case series [3,4,5].
T98 11687-11839 Sentence denotes The role of β-d-glucan and the Aspergillus-specific lateral flow device (LFD) as an adjunct to the diagnosis of IPA in COVID-19 is not yet clear [2,23].
T99 11840-11934 Sentence denotes Serum β-d-glucan was persistently strongly positive in this patient over the course of a week.
T100 11935-12182 Sentence denotes The specificity for invasive fungal disease of β-d-glucan testing in a mixed ICU population has been shown to be high (86%), with two consecutive positive results [29] compared to those with only fungal colonization and no invasive fungal disease.
T101 12183-12333 Sentence denotes In addition, multiple other studies report a good sensitivity for the diagnosis of invasive aspergillosis in critically ill patients [30,31,32,33,34].
T102 12334-12478 Sentence denotes BAL β-d-glucan in the ICU setting is, however, not recommended, due to its poor specificity and confounders causing false positive results [35].
T103 12479-12559 Sentence denotes The LFD is particularly interesting in the ICU due to its short turnaround time.
T104 12560-12742 Sentence denotes It has demonstrated a higher sensitivity but lower specificity in BAL fluids compared to galactomannan [36] and β-d-glucan [37] in IPA-probable and proven immunocompromised patients.
T105 12743-12891 Sentence denotes In the ICU setting, however, LFD is suggested to have a lower sensitivity but comparable specificity to galactomannan testing in BAL fluids [35,38].
T106 12892-12984 Sentence denotes Noteworthily, a negative predictive value of >96% has been reported in the ICU setting [39].
T107 12985-13158 Sentence denotes We used the OLM lateral flow device (AspLFD) on sequential patient tracheal aspirates, yielding positive results on all samples confirming the positive galactomannan result.
T108 13159-13337 Sentence denotes Although suitable for its negative predictive value or as an additional diagnostic measure, further evaluation of lateral flow technology in critically ill patients is warranted.
T109 13338-13438 Sentence denotes Altogether, we describe the clinical course of the first reported patient with azole-resistant CAPA.
T110 13439-13609 Sentence denotes The contribution of A. fumigatus to this fatal COVID-19 course is highly likely, although autopsy was not performed, as in all previously reported CAPA cases [3,4,5,6,7].