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PMC:7239617 JSONTXT 18 Projects

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Id Subject Object Predicate Lexical cue
T1 0-96 Sentence denotes Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19
T2 98-1123 Sentence denotes About 5% of patients with coronavirus disease 2019 (COVID-19) require intensive care unit (ICU) management.1 These patients are at high risk of developing secondary infections including invasive pulmonary aspergillosis (IPA).2 First reported with H1N1 influenza, IPA represents a frequent (20–30%) and early-onset complication (median, 3 days post-ICU admission) in critically ill patients with influenza, leading to enhanced illness severity and mortality (40–60%).3, 4 Most cases have been observed in non-immunocompromised patients, questioning the applicability of the European Organization for Research and Treatment of Cancer Mycoses Study Group (EORTC-MSG) consensus criteria used to define aspergillosis in immunocompromised patients.5 Therefore, an algorithm to discriminate Aspergillus spp colonisation from putative IPA was developed for patients in ICU on the basis of mycological criteria combining culture from respiratory specimens and galactomannan detection in the bronchoalveolar lavage (BAL) and serum.4, 6
T3 1124-1297 Sentence denotes Parallelling what has been reported in influenza patients, we designed this prospective observational study to investigate IPA risk in critically ill patients with COVID-19.
T4 1298-1566 Sentence denotes The patients were classified by means of the EORTC-MSG criteria5 (if immunocompromised) or the influenza-associated IPA criteria4 combined with serum β-D-glucan and quantitative real-time PCR (qPCR)7 done in the serum or pulmonary specimens (if non-immunocompromised).
T5 1567-1927 Sentence denotes Putative IPA was considered if Aspergillus spp were identified in BAL culture; or if two of the following conditions were met (ie, presence of Aspergillus spp in bronchial aspiration [BA] culture; positive Aspergillus fumigatus qPCR in BAL, BA, or serum;8 galactomannan index >0·8 in BAL;5 galactomannan index >0·5 in serum; and β-D-glucan >80 pg/mL in serum).
T6 1928-2062 Sentence denotes 27 successive mechanically ventilated patients with COVID-19 (18 male and nine female, median age 63 years [IQR 56-71]) were included.
T7 2063-2146 Sentence denotes Specimens (20 BALs and seven BAs) were obtained on day 3 [IQR 1–6] post-intubation.
T8 2147-2261 Sentence denotes Probable IPAs were diagnosed in one patient (4%) and putative IPAs were diagnosed in eight patients (30%; table ).
T9 2262-2402 Sentence denotes Putative IPA diagnosis relied on Aspergillus spp identification in BAL culture (n=2) and validation of 2 or more mycological criteria (n=6).
T10 2403-2546 Sentence denotes Table Clinical characteristics of nine critically ill patients with COVID-19 probable (n=1) and putative invasive pulmonary aspergillosis (n=8)
T11 2547-2640 Sentence denotes Putative invasive pulmonary aspergillosis patients (sex, age) Probable IPA patient (sex, age)
T12 2641-2890 Sentence denotes Patient 1 (male, 53 years) Patient 2 (female, 59 years) Patient3 (female, 69 years) Patient 4 (female, 63 years) Patient 5 (male, 43 years) Patient 6 (male, 79 years) Patient 7 (male, 77 years) Patient 8 (female, 75 years) Patient 9 (male, 47 years)
T13 2891-3140 Sentence denotes Risk factors of severe COVID-19 Hypertension, obesity, ischaemic heart disease Hypertension, diabetes, obesity Hypertension, obesity Hypertension, diabetes, ischaemic heart disease Asthma Hypertension Hypertension, asthma Hypertension, diabetes None
T14 3141-3221 Sentence denotes EORTC risk factors None None None None Steroids None None None Myeloma, steroids
T15 3222-3263 Sentence denotes APACHE II score 26 16 11 20 8 16 25 21 10
T16 3264-3503 Sentence denotes Thoracic CT-scan/x-ray* Typical COVID-19 Typical COVID-19 Typical COVID-19 Typical COVID-19 Typical COVID-19 Typical COVID-19, segmental lung atelectasis Typical COVID-19, emphysema Typical COVID-19 Typical COVID-19 + one peripheral nodule
T17 3504-3620 Sentence denotes Anti-COVID-19 therapies LPV–RTV LPV–RTV, AZI LPV–RTV LPV–RTV AZI LPV–RTV, HCQ, AZI LPV–RTV, HCQ, AZI LPV–RTV, AZI No
T18 3621-3682 Sentence denotes Steroids to treat pneumonia† Yes No Yes Yes No Yes Yes Yes No
T19 3683-3738 Sentence denotes Renal replacement therapy Yes No No Yes No No Yes No No
T20 3739-3785 Sentence denotes Vasopressor Yes Yes Yes Yes No Yes Yes Yes Yes
T21 3786-3839 Sentence denotes Pulmonary specimen‡ BAL BAL BA BAL BAL BAL BAL BAL BA
T22 3840-3882 Sentence denotes Invasive pulmonary aspergillosis diagnosis
T23 3883-3913 Sentence denotes BAL culture§ − + + − + + + + +
T24 3914-3956 Sentence denotes BAL/BA qPCR¶ − − 23·9 − − 34·5 29·0 31·7 −
T25 3957-4021 Sentence denotes BAL galactomannan index 0·89 0·03 ND 0·15 0·12 0·05 3·91 0·36 ND
T26 4022-4052 Sentence denotes Serum qPCR¶ − − − ND − − − − −
T27 4053-4101 Sentence denotes β-D-glucan, pg/mL 523 ND 7·8 105 7 23 135 450 14
T28 4102-4172 Sentence denotes Serum galactomannan index 0·13 0·04 0·03 0·51 0·04 0·02 0·37 0·37 0·09
T29 4173-4221 Sentence denotes Number of mycological criteria 2 1 2 2 1 2 3 3 1
T30 4222-4283 Sentence denotes Antifungal therapy None None None None None None VRC CSP None
T31 4284-4378 Sentence denotes Outcome Alive Alive Alive Death (day 0) Alive Alive Death (day 18) Death (day 11) Death day 3)
T32 4379-4444 Sentence denotes EORTC=European Organization for Research and Treatment of Cancer.
T33 4445-4497 Sentence denotes APACHE= Acute Physiology and Chronic Health Enquiry.
T34 4498-4537 Sentence denotes LPV–RTV=lopnavir–ritonavir combination.
T35 4538-4555 Sentence denotes AZI=azithromycin.
T36 4556-4579 Sentence denotes HCQ=hydroxychloroquine.
T37 4580-4607 Sentence denotes BAL=Bronchoalveolar lavage.
T38 4608-4632 Sentence denotes BA=bronchial aspiration.
T39 4633-4645 Sentence denotes ND=not done.
T40 4646-4663 Sentence denotes VRC=voriconazole.
T41 4664-4680 Sentence denotes CSP=caspofungin.
T42 4681-4772 Sentence denotes * Thoracic CT scan was done in Pt3, Pt4, Pt5, 5 days (median) before respiratory specimens.
T43 4773-4897 Sentence denotes † Dexamethasone intravenous dose of 20 mg once daily from day 1 to day 5, followed by 10 mg once daily from day 6 to day 10;
T44 4898-4953 Sentence denotes ‡ No endotracheal or endobronchial lesion was observed.
T45 4954-5021 Sentence denotes § −=negative; +=positive with Aspergillus fumigatus identification.
T46 5022-5116 Sentence denotes ¶ qPCR=quantitative real-time PCR (−, negative; if positive, number of quantification cycles).
T47 5117-5233 Sentence denotes History of hypertension was reported more frequently in the patients with IPA (seven of nine vs six of 18, p=0·046).
T48 5234-5558 Sentence denotes No other significant differences were observed in terms of age, EORTC-MSG risk factors for IPA, time between onset of symptoms and intubation and time between onset of symptoms or intubation and Aspergillus spp respiratory specimen collection, severity, laboratory data, non-COVID CT-scan images, and steroid administration.
T49 5559-5631 Sentence denotes Antifungal therapy was initiated in two of nine (22%) patients with IPA.
T50 5632-5744 Sentence denotes Mortality rate did not differ between IPA and non-IPA patients (four of nine [44%] vs seven of 18 [39%], p=0·99.
T51 5745-6083 Sentence denotes We found putative IPA in almost one-third of our mechanically ventilated patients with COVID-19—a similar prevalence to that observed in patients with influenza.3, 4 One patient with myeloma presented with probable IPA on the basis of EORTC criteria5 with one nodule on chest x-rays in addition to the typical COVID-19-attributed lesions.
T52 6084-6239 Sentence denotes Since CT and BAL are extremely difficult to do in patients with life-threatening COVID-19, mycological data collection is essential to allow IPA diagnosis.
T53 6240-6495 Sentence denotes We strongly support adding β-D-glucan in serum and qPCR in serum and respiratory specimens to the accepted mycological work-up (ie, BAL culture and galactomannan testing)4, 6 until the most sensitive and specific biomarkers are identified in this setting.
T54 6496-6708 Sentence denotes Serum galactomannan was negative in eight of nine (89%) patients, suggesting a lesser degree of Aspergillus invasiveness or early IPA diagnosis, since respiratory specimens were obtained shortly after intubation.
T55 6709-6850 Sentence denotes Galactomannan was negative in our two patients receiving hydroxychloroquine, which is thought to have a negative effect on this measurement.9
T56 6851-6933 Sentence denotes We believe that IPA is more probable if at least two mycological criteria are met.
T57 6934-7066 Sentence denotes However, three patients had Aspergillus fumigatus culture without positive qPCR detection or galactomannan antigen in the BAL or BA.
T58 7067-7277 Sentence denotes Not considering positive culture alone as a diagnostic criterion in accordance with what is accepted,4, 6 would have resulted in underestimating the frequency of putative IPA (22% rather than 30% in our study).
T59 7278-7460 Sentence denotes Despite similar IPA prevalence in critically ill patients with COVID-19 and influenza, the contribution of Aspergillus to the patient presentation in each illness might be different.
T60 7461-7662 Sentence denotes In our patients with IPA, death, including in the two patients who received anti-Aspergillus treatment, was not related to aspergillosis but to bacterial septic shock complicated by multiorgan failure.
T61 7663-7810 Sentence denotes Consistent with others,10, 11 our findings support systematic screening for Aspergillus infection markers in critically ill patients with COVID-19.
T62 7811-8221 Sentence denotes Although oseltamivir-induced inhibition of the host neuraminidase activity has been suggested as a possible molecular mechanism leading to decreased anti-Aspergillus protective immunity in patients with influenza, the exact reasons for increased vulnerability of the patients with COVID-19 to Aspergillus remain to be identified as well as the contribution of Aspergillus to COVID-19-related lung inflammation.
T63 8223-8266 Sentence denotes The authors declare no competing interests.
T64 8267-8385 Sentence denotes This study was part of the COVID-ICU registry and the French COVID-19 cohort registry done by the REACTing consortium.
T65 8386-8491 Sentence denotes Our institutional ethics committee approved the study (IDRCB, 2020-A00256-33; CPP, 11-20 20.02.04.68737).