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Id Subject Object Predicate Lexical cue
T1 0-82 Sentence denotes Confronting and mitigating the risk of COVID-19 associated pulmonary aspergillosis
T2 83-149 Sentence denotes Mitigating the risk of COVID-19 associated pulmonary aspergillosis
T3 151-302 Sentence denotes The coronavirus disease 2019 (COVID-19) virus caused a wide spectrum of disease in healthy individuals, as well as those with common comorbidities [1].
T4 303-511 Sentence denotes Severe COVID-19 is characterised by acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis, treatment of which may require mechanical ventilation or extracorporeal membrane oxygenation [2].
T5 512-745 Sentence denotes Clinicians are alert to the possibility of bacterial co-infection as a complication of lower respiratory tract viral infection; for example, a recent review found that 72% of patients with COVID-19 received antimicrobial therapy [3].
T6 746-879 Sentence denotes However, the risk of fungal co-infection, in particular COVID-19 associated pulmonary aspergillosis (CAPA), remains underappreciated.
T7 881-1116 Sentence denotes Cases of COVID-19 associated pulmonary aspergillosis (CAPA) are being increasingly reported and physicians treating patients with COVID-19-related lung disease need to actively consider these fungal co-infections https://bit.ly/3feuGsQ
T8 1118-1269 Sentence denotes The coronavirus disease 2019 (COVID-19) virus caused a wide spectrum of disease in healthy individuals, as well as those with common comorbidities [1].
T9 1270-1478 Sentence denotes Severe COVID-19 is characterised by acute respiratory distress syndrome (ARDS) secondary to viral pneumonitis, treatment of which may require mechanical ventilation or extracorporeal membrane oxygenation [2].
T10 1479-1712 Sentence denotes Clinicians are alert to the possibility of bacterial co-infection as a complication of lower respiratory tract viral infection; for example, a recent review found that 72% of patients with COVID-19 received antimicrobial therapy [3].
T11 1713-1846 Sentence denotes However, the risk of fungal co-infection, in particular COVID-19 associated pulmonary aspergillosis (CAPA), remains underappreciated.
T12 1847-2081 Sentence denotes Fungal disease consistent with invasive aspergillosis has been observed with other severe coronaviruses such as severe acute respiratory syndrome-coronavirus (SARS-CoV) 2003 [4, 5] and Middle East Respiratory Syndrome-coronavirus [6].
T13 2082-2188 Sentence denotes From the outset of the COVID-19 pandemic, there were warning signs of secondary invasive fungal infection.
T14 2189-2498 Sentence denotes Aspergillus flavus was isolated from the respiratory tract in one out of 99 patients in the first COVID-19 cohort from Wuhan, China to be reported in any detail [2] and Aspergillus spp. were isolated from two (3.8%) out of 52 patients in a subsequent cohort of critically unwell patients from this region [7].
T15 2499-2697 Sentence denotes More recently, retrospective case series from Belgium [8], France [9], The Netherlands [10] and Germany [11] have reported evidence of CAPA in an alarming 20–35% of mechanically ventilated patients.
T16 2699-2703 Sentence denotes CAPA
T17 2704-2935 Sentence denotes Influenza-associated pulmonary aspergillosis (IAPA) presents a known risk to critically unwell patients with influenza [12–14] and the clinical course of COVID-19 shows many features that are shared with severe influenza infection.
T18 2936-3101 Sentence denotes These include ARDS, lymphopenia, bilateral pulmonary infiltrates, systemic pro-inflammatory cytokine responses and sepsis leading to multiple organ failure [14, 15].
T19 3102-3230 Sentence denotes It is therefore reasonable to suspect that patients with severe COVID-19 may be similarly susceptible to invasive aspergillosis.
T20 3231-3470 Sentence denotes Corticosteroid use is an important acquired immunological risk factor for IAPA [16] and, during the SARS-CoV 2003 epidemic, there were case reports of patients developing SARS-associated invasive aspergillosis after corticosteroid use [5].
T21 3471-3598 Sentence denotes Corticosteroid use has been reported in hospitalised patients with COVID-19 [1] and may further contribute to the risk of CAPA.
T22 3599-3935 Sentence denotes Importantly, the recent finding by the UK RECOVERY trial (ISRCTN50189673) [17] of a one-third mortality reduction conferred by dexamethasone in ventilated patients with COVID-19, while leading to a crucial new therapeutic avenue, may increase the risk of patients acquiring CAPA and emphasises the need for enhanced fungal surveillance.
T23 3936-4037 Sentence denotes Table 1 summarises individual patient-level data in 33 cases of CAPA that have been reported to date.
T24 4038-4212 Sentence denotes The median (interquartile range) age of cases is 70 (57–75) years, of whom only two (6%) had a European Organization for Research and Treatment of Cancer (EORTC) host factor.
T25 4213-4492 Sentence denotes Of these 16 (48%) had exposure to inhaled or systemic corticosteroids, 10 (30%) had diabetes and nine (27%) had underlying chronic lung disease; COPD (n=5), asthma (n=3), bullous emphysema (n=1), pulmonary fibrosis (n=1) and post-radiotherapy for nonsmall-cell lung cancer (n=1).
T26 4493-4662 Sentence denotes CAPA was diagnosed a median (interquartile range) 5.5 (4.3–9) days after intensive care unit (ICU) admission and 21 (63.6%) patients had died by the time of publication.
T27 4663-4914 Sentence denotes This mortality is in excess of most cohorts of ventilated patients with COVID-19, as a comparison in the UK ISARIC cohort 618 (37%) out of 1658 ventilated patients had died by the time of publication (17% discharged and 46% still receiving care) [23].
T28 4915-5063 Sentence denotes TABLE 1 Summary of reported cases of coronavirus disease 2019 (COVID-19) associated pulmonary aspergillosis in the intensive care unit (ICU) setting
T29 5064-5246 Sentence denotes Location [ref.] Age years Sex IPA risk factors Radiology BAL culture TA culture BAL GM Serum GM Other diagnostics Onset days post-ICU EORTC status Mod AspICU status Treatment Outcome
T30 5247-5472 Sentence denotes Cologne, Germany [11] 62 F Ex-smoker, moderate COPD, inhaled steroids Ground-glass opacities, crazy paving, peripheral nodular consolidation A. fumigatus NR (+) >2.5 (-) BAL PCR A. fumigatus NR No host factor# Putative V Died
T31 5473-5631 Sentence denotes Cologne, Germany [11] 70 M Ex-smoker Ground-glass opacities, occasional nodules (-) NR (+) >2.5 (+) 0.7 BAL PCR A. fumigatus NR No host factor Putative I Died
T32 5632-5884 Sentence denotes Cologne, Germany [11] 54 M Diabetes, systemic corticosteroids0.4 mg·kg−1·day−1×13 days Ground-glass opacities, nodular infiltrates with cavities, air crescent sign (-) A. fumigatus (+) >2.5 (-) BAL PCR A. fumigatus NR No host factor Putative C, V Alive
T33 5885-6153 Sentence denotes Cologne, Germany [11] 73 M Smoker, bullous emphysema, severe COPD, inhaled steroids Ground-glass opacities, occasional nodules, known bullous emphysema ND A. fumigatus ND (-) TA PCR A. fumigatus NR No host factor Putative only if TA considered equivalent to BAL V Died
T34 6154-6361 Sentence denotes Cologne, Germany [11] 54 F None Ground-glass opacities, crazy paving, central and peripheral consolidation, smaller nodular infiltrates ND (-) ND (+) 2.7, 1.3 TA PCR (-) NR No host factor Putative C, V Alive
T35 6362-6541 Sentence denotes Munich, Germany [18] 80 M Pulmonary fibrosis Typical signs for COVID-19 pneumonia but no specific signs for IPA A. fumigatus NR (+) >6 (+) 1.5 5 No host factor Putative L-AmB Died
T36 6542-6703 Sentence denotes Munich, Germany [18] 70 M None Typical signs for COVID-19 pneumonia but no specific signs for IPA A. fumigatus NR (+) >6 (-) 6 No host factor Putative L-AmB Died
T37 6704-6919 Sentence denotes Paris, France [19] 74 M Myelodysplastic syndrome NR ND A. fumigatus ND (-) x2 TA PCR A. fumigatus x2, TA GM (-)×1, BDG and serum PCR (-) x2 4 No host factor Putative only if TA considered equivalent to BAL None Died
T38 6920-7155 Sentence denotes Paris, France [9] 53 M Dexamethasone 20 mg·day−1 days 1–5, 10 mg·day−1 days 6–10 Typical COVID-19 (-) NR (-) 0.89 (-) BAL PCR (-), Serum PCR (-), BDG (+) >500 NR No host factor Putative only if BAL GM cut-off lowered to >0.8 None Alive
T39 7156-7333 Sentence denotes Paris, France [9] 59 F Diabetes Typical COVID-19 A. fumigatus NR (-) (-) BAL PCR (-), serum PCR (-) NR No host factor Putative but note BAL culture (+) but BAL GM (-) None Alive
T40 7334-7576 Sentence denotes Paris, France [9] 69 F Dexamethasone 20 mg·day−1 days 1–5, 10 mg·day−1 days 6–10 Typical COVID-19 ND A. fumigatus ND (-) TA PCR A. fumigatus, serum PCR (-), BDG (-) NR No host factor Putative only if TA considered equivalent to BAL None Alive
T41 7577-7802 Sentence denotes Paris, France [9] 63 F Diabetes, dexamethasone 20 mg·day−1 days 1–5, 10 mg·day−1 days 6–10 Typical COVID-19 (-) NR (-) (+) 0.51 BAL PCR (-), BDG (+) 105 NR No host factor Putative but relies on serum GM of only 0.51 None Died
T42 7803-8004 Sentence denotes Paris, France [9] 43 M Asthma, corticosteroids Typical COVID-19 A. fumigatus NR (-) (-) BAL PCR (-), serum PCR (-), BDG (-) NR No host factor Putative but note BAL culture (+) but BAL GM (-) None Alive
T43 8005-8283 Sentence denotes Paris, France [9] 79 M Diabetes, Dexamethasone 20 mg·d−1 days 1–5, 10 mg·d−1 days 6–10 Typical COVID-19, segmental lung atelectasis A. fumigatus NR (-) (-) BAL PCR A. fumigatus, serum PCR (-), BDG (-) NR No host factor Putative but note BAL culture (+) but BAL GM (-) None Alive
T44 8284-8513 Sentence denotes Paris, France [9] 77 M Asthma, dexamethasone 20 mg·day−1 days 1–5, 10 mg·day−1 days 6–10 “Typical COVID-19”, emphysema A. fumigatus NR (+) 3.9 (-) BAL PCR A. fumigatus, serum PCR (-), BDG (+) 135 NR No host factor Putative V Died
T45 8514-8769 Sentence denotes Paris, France [9] 75 F Diabetes, dexamethasone 20 mg·day−1 days 1–5, 10 mg·day−1 days 6–10 Typical COVID-19 A. fumigatus NR (-) (-) BAL PCR, A. fumigatus, serum PCR (-), BDG (+) 450 NR No host factor Putative but note BAL culture (+) but BAL GM (-) C Died
T46 8770-8995 Sentence denotes Paris, France [9] 47 M Myeloma, corticosteroids Typical COVID-19, one peripheral nodule ND A. fumigatus ND (-) TA PCR A. fumigatus, serum PCR (-), BDG (-) NR Probable Putative only if TA considered equivalent to BAL None Died
T47 8996-9328 Sentence denotes Graz, Austria [20] 70 M Moderate COPD, steroid inhaler, obstructive sleep apnoea, diabetes Ground-glass opacities, crazy paving, reversed halo sign, progression of the bilateral infiltrates on day 2 chest radiography ND A. fumigatus ND (-) TA LFD (+), BDG (-) 3 No host factor Putative only if TA considered equivalent to BAL V Died
T48 9329-9458 Sentence denotes Antwerp, Belgium [8] 86 M None ND ND A. flavus ND (-) 9 No host factor Putative only if TA considered equivalent to BAL None Died
T49 9459-9581 Sentence denotes Antwerp, Belgium [8] 38 M None (+) A. fumigatus NR (+) >2.8 (-) Histology from bronchoscopy (+) 6 Proven Proven V, I Alive
T50 9582-9704 Sentence denotes Antwerp, Belgium [8] 62 M Diabetes ND A. fumigatus NR (+) >2.0 (-) Histology from bronchoscopy (+) 16 Proven Proven V Died
T51 9705-9827 Sentence denotes Antwerp, Belgium [8] 73 M Diabetes ND A. fumigatus NR (+) >2.8 (-) Histology from bronchoscopy (+) 5 Proven Proven V Alive
T52 9828-10000 Sentence denotes Antwerp, Belgium [8] 77 M Diabetes, chronic corticosteroids for pemphigus foliaceous ND A. fumigatus NR (+) 2.79 (-) Histology from bronchoscopy (+) 2 Proven Proven V Alive
T53 10001-10197 Sentence denotes Antwerp, Belgium [8] 55 M HIV (CD4 count >250, viral load <20) copies) ND (-) NR (-) (+) 0.8 Histology from bronchoscopy (-) 13 No host factor Putative but relies on serum GM of only 0.8 V, I Died
T54 10198-10305 Sentence denotes Antwerp, Belgium [8] 75 M AML with IPA 2012 ND A. fumigatus NR (+) 2.63 ND 8 No host factor Putative V Died
T55 10306-10555 Sentence denotes Breda, The Netherlands [10] 83 M Prednisolone 0.13 mg·kg−1·day−1×28 days for cardiomyopathy NR ND A. fumigatus ND (-) 3 Probable if steroid requirement reduced to <0.3 mg·kg−1·day−1 Putative only if TA considered equivalent to BAL V+A, or L-AmB Died
T56 10556-10774 Sentence denotes Breda, The Netherlands [10] 67 M Severe COPD, Post RT for NSCLC 2014, prednisolone 0.37 mg·kg−1·day−1×2 days NR ND A. fumigatus ND ND 3 No host factor Putative only if TA considered equivalent to BAL V+A, or L-AmB Died
T57 10775-10946 Sentence denotes Breda, The Netherlands [10] 75 M Moderate COPD NR A. fumigatus NR (+) 4.0 ND Mucoid white sputum left bronchus at bronchoscopy 5 No host factor Putative V+A, or L-AmB Died
T58 10947-11053 Sentence denotes Breda, The Netherlands [10] 43 M None NR (-) NR (+) 3.8 (-) 14 No host factor Putative V+A, or L-AmB Alive
T59 11054-11187 Sentence denotes Breda, The Netherlands [10] 57 M Asthma, inhaled steroids NR A. fumigatus NR (+) 1.6 (-) 5 No host factor Putative V+A, or L-AmB Died
T60 11188-11337 Sentence denotes Breda, The Netherlands [10] 58 M None NR ND A. fumigatus ND ND 28 No host factor Putative only if TA considered equivalent to BAL V+A, or L-AmB Alive
T61 11338-11544 Sentence denotes Paris, France [21] 80 M None Pleural effusions, alveolar condensation, ground-glass opacities, pulmonary cysts ND A. flavus ND ND NR No host factor Putative only if TA considered equivalent to BAL V, I Died
T62 11545-11756 Sentence denotes Milan, Italy [22] 73 M Diabetes Interstitial opacities with right upper lobe focal consolidation which progressively worsened A. fumigatus NR ND (+) 8.6 Lung histology from PM (+), PM tissue PCR Aspergillus spp.
T63 11757-11783 Sentence denotes 9 Proven Proven L-AmB Died
T64 11784-11817 Sentence denotes Summary Median (IQR)70 (57–75) M:
T65 11818-12280 Sentence denotes 26 (79%) out of 33 EORTC host factor: n=2 (6%); inhaled/systemic steroid exposure: n=16 (48%); diabetes: n=10 (30%); chronic lung disease: n=9 (27%) Nodules: n=6 (31.6%), cavity/halo-sign: n=2 (10.5%) 16 (72.7%) out of 22 with BAL 14 (66.7%) out of 21 with BAL GM 6 (21.4%) out of 28 with serum GM Median (IQR)5.5 (4.3–9) Proven: n=5; probable: n=1; no host factor: n=27 Proven: n=5; putative: n=11; putative with caveats: n=17 24 (72.7%) treated 21 (63.6%) died
T66 12281-12397 Sentence denotes IPA: invasive pulmonary aspergillosis; BAL: bronchoalveolar lavage; TA: tracheal aspirate; GM: galactomannan; EORTC:
T67 12398-12548 Sentence denotes European Organization for Research and Treatment of Cancer; AspICU: clinical criteria to diagnose IPA; M: male; F: female; BDG: (1–3)-β-D-glucan; LFD:
T68 12549-13422 Sentence denotes Aspergillus lateral-flow device; PM: post mortem; AML: acute myeloid leukaemia; RT: radiotherapy; NSCLC: nonsmall-cell lung cancer; NR: not recorded; V: voriconazole; I: isavuconazole; L-AmB: liposomal amphotericin B; C: caspofungin; A: anidulafungin; ND: no data; (+): positive result; (-): negative result. #: without histological evidence of “proven” IPA a patient host factor (e.g. recent neutropenia, haematological malignancy) is required to meet the probable/possible definition, corticosteroids must be given at ≥0.3 mg·kg−1 for ≥3 weeks to classify as a host factor result.Invasive aspergillosis is difficult to diagnose in critically unwell patients without traditional host factors because radiological changes are usually nonspecific (e.g. infiltrates, consolidation or nodules), with features such as halo sign, air-crescent sign or cavitation being rare [24].
T69 13423-13734 Sentence denotes For these reasons Schauwvlieghe et al. [13] developed the modified AspICU criteria to help diagnose IAPA which (in the absence of histology) essentially relies on mycological evidence of Aspergillus spp. in the form of a positive bronchoalveolar lavage (BAL) culture or positive galactomannan (GM) in serum/BAL.
T70 13735-13927 Sentence denotes Applying these modified AspICU criteria, five cases of CAPA in table 1 were “proven”, 11 “putative” and 17 might be considered putative but with caveats which have been described in the table.
T71 13928-14107 Sentence denotes For example, in many cases a tracheal aspirate, rather than BAL, provided the only mycological evidence of invasive aspergillosis (in the absence of tracheobronchitis/cavitation).
T72 14108-14293 Sentence denotes There should therefore be caution about over-estimating the incidence of CAPA from such case series, which may include some patients with aspergillus colonisation or contamination only.
T73 14294-14736 Sentence denotes In the study by Alanio et al. [9] which reported evidence of CAPA in nine (33%) out of 27 ventilated patients who underwent BAL/tracheal aspirate, one case was defined based on a BAL GM of 0.89 (below the usual cut-off of 1.0), two based on tracheal aspirate rather than BAL culture, one based on a serum GM of 0.51 (cut-off being 0.50) and in four cases BAL culture was positive but BAL GM negative, which suggests a lack of tissue invasion.
T74 14737-14818 Sentence denotes Indeed, out of seven cases that were not treated with antifungals, five survived.
T75 14819-15018 Sentence denotes Accordingly, larger, prospective, multi-site studies are needed to refine the AspICU criteria for patients with COVID-19, as well as to estimate incidence and the impact of CAPA on survival [25, 26].
T76 15020-15046 Sentence denotes Diagnosis and risk of CAPA
T77 15047-15188 Sentence denotes Bearing these observations in mind, we argue that critically ill patients with COVID-19 and progressive features should be screened for CAPA.
T78 15189-15396 Sentence denotes We acknowledge that acquiring and handling clinical samples for microbiology is very challenging given the Hazard Group 3 rating of the SARS-CoV-2 virus, alongside an overburdened critical care service [27].
T79 15397-15608 Sentence denotes Ideally, screening for CAPA entails using a combination of computed tomography chest imaging and Aspergillus antigen tests on BAL and serum including GM ELISA or lateral-flow tests [28], or aspergillus PCR [29].
T80 15609-15793 Sentence denotes Whilst characteristic CT features of invasive aspergillosis such as nodules with halo sign were seen in 17.6% of severely ill COVID-19 patients, they were not confirmed to be IPA [30].
T81 15794-16082 Sentence denotes Given the lack of typical invasive aspergillosis features on CT in IAPA, the absence of classical findings such as cavitation should not be used to exclude CAPA; however, their presence can help support the diagnosis and reduce the burden of evidence placed on mycological investigations.
T82 16083-16289 Sentence denotes In a study of 26 ICU patients that were diagnosed with proven (non-CAPA/IAPA) IPA post mortem, serum GM had only 25% sensitivity in those that were not neutropenic (versus 70% in neutropenic patients) [31].
T83 16290-16346 Sentence denotes In contrast, BAL GM was 88–90% sensitive in both groups.
T84 16347-16529 Sentence denotes In the IAPA study by Schauwvlieghe et al. [13] serum GM testing performed better with 20 (65%) out of 31 positive cases, however BAL GM remained superior at 67 (88%) out of 76 cases.
T85 16530-16699 Sentence denotes In CAPA cases reported to date (table 1), BAL culture and GM had a sensitivity of 72.7% and 66.7%, respectively, but serum GM was positive in only six (21.4%) out of 28.
T86 16700-16883 Sentence denotes Moreover, of the five cases of proven CAPA reported to date, four were serum GM negative (table 1) [8], indicating that serum GM test performance might be inferior in diagnosing CAPA.
T87 16884-17167 Sentence denotes Therefore, bronchoscopy, including tracheobronchial inspection and BAL sampling for culture and GM should be the diagnostic gold standards whenever CAPA is suspected, providing this is compatible with local infection prevention and control guidance for aerosol-generating procedures.
T88 17168-17287 Sentence denotes A positive BAL GM (index >1.0) would be indicative of CAPA, whereas if the index is <0.5 CAPA is much less likely [31].
T89 17288-17425 Sentence denotes A positive serum GM result (≥ 0.5) would be highly suspicious for CAPA but a negative result should not be used to exclude the diagnosis.
T90 17426-17644 Sentence denotes Novel lateral-flow antigen tests may represent a locally implementable alternative to GM ELISA in the CL3 laboratory, but currently require validation in ICU patients without EORTC host factors including COVID-19 [28].
T91 17645-17865 Sentence denotes An Aspergillus-specific PCR test [29] may also be helpful and if positive could also lead to the application of molecular testing for the recognised markers of clinically or environmentally derived azole resistance [32].
T92 17866-17991 Sentence denotes A (1–3)-β-D-glucan (BDG) test on a serum sample is an easily obtained, early screening test when there is a suspicion of IPA.
T93 17992-18315 Sentence denotes Although performance might be superior to serum Aspergillus antigen testing for the detection of IPA in the ICU [33], BDG negativity cannot be used to rule out infection, with a 77% sensitivity determined across a heterogeneous population of invasive aspergillosis patients, and performance in CAPA as yet to be determined.
T94 18316-18589 Sentence denotes BDG positivity can occur due to a number of reasons in this patient cohort, however serial positive tests increases specificity and should prompt a diagnostic work-up including computed tomography and bronchoscopy and testing for Aspergillus antigen as outlined above [34].
T95 18590-18815 Sentence denotes While initiating antifungal treatment pre-emptively based on BDG positivity may be an improvement on empirical therapy, every effort should be made to utilise other more specific diagnostic tests to complement the BDG result.
T96 18816-19053 Sentence denotes Current guidelines advise against routine diagnostic bronchoscopy due to the risk of aerosol generation; recommending it only in patients in whom nasopharyngeal cultures are negative and BAL sampling will change clinical management [35].
T97 19054-19250 Sentence denotes In practice many patients with suspected CAPA undergo endotracheal sampling or non-directed BAL sampling only, and it is important that any case definition proposed for CAPA reflects this reality.
T98 19251-19472 Sentence denotes To acknowledge this, we propose a screening and diagnostic algorithm for CAPA, which has clinical (respiratory) deterioration and/or positive aspergillus sputum, or tracheal aspirate culture as its entry point (figure 1).
T99 19473-19717 Sentence denotes Although the host risk factors and clinical characteristics of CAPA are not yet understood, those individuals fulfilling the criteria for proven or probable aspergillosis [13, 14] should then be treated according to current guidelines [36, 37].
T100 19718-19993 Sentence denotes Importantly, now that adjunctive use of dexamethasone is likely to become widespread in the treatment of patients with severe COVID-19 [17], intensified screening for invasive aspergillosis is indicated to study the possible association between corticosteroid usage and CAPA.
T101 19994-20118 Sentence denotes FIGURE 1 Proposed screening and diagnostic algorithm for coronavirus disease-2019 associated pulmonary aspergillosis (CAPA).
T102 20119-20292 Sentence denotes BAL: bronchoalveolar lavage; BDG: (1–3)-β-D-glucan; TA: tracheal aspirate; Asp Ag: aspergillus antigen; AF: antifungal; IA: invasive aspergillosis; GM: galactomannan; EORTC:
T103 20293-20399 Sentence denotes European Organization for Research and Treatment of Cancer; NBL: non-directed bronchoalveolar lavage; PCP:
T104 20400-20655 Sentence denotes Pneumocystis pneumonia.Finally, the use of immunomodulatory drugs such as anakinra (recombinant interleukin-1Ra), tocilizumab (anti-interleukin-6) and Janus kinase inhibitors, currently undergoing trials for COVID-19, may also predispose patients to CAPA.
T105 20656-20879 Sentence denotes There is also an increased risk of Aspergillus exposure for patients who are treated in hospital wards or makeshift “hospital” facilities that do not meet ICU specifications for appropriate room ventilation and air changes.
T106 20880-21074 Sentence denotes It is also worth bearing in mind that pulmonary aspergillosis could develop into a chronic cavitary disease in a subset of patients, perhaps in those developing post-COVID-19 pulmonary fibrosis.
T107 21075-21264 Sentence denotes For these reasons, clinicians following up patients manifesting chronic respiratory problems following their primary COVID-19 infection should bear in mind longer term fungal complications.
T108 21266-21276 Sentence denotes Conclusion
T109 21277-21401 Sentence denotes Fungal infections present an additional threat in the challenging task of managing COVID-19 patients in outbreak conditions.
T110 21402-21603 Sentence denotes The pandemic of SARS-CoV-2 virus will undoubtedly involve CAPA, and the use of immunomodulatory therapy and impact of overburdened critical care services during this pandemic may exaggerate its impact.
T111 21604-21898 Sentence denotes More research is needed on the epidemiology and diagnosis of CAPA in patients with COVID-19, a need that is partially met as ongoing prospective multi-site clinical studies are extended to include this cohort (e.g. AspiFlu) [25] or are launched (CAPA) [26] in response to the COVID-19 pandemic.
T112 21900-21913 Sentence denotes Shareable PDF
T113 21914-21960 Sentence denotes This one-page PDF can be shared freely online.
T114 21961-21999 Sentence denotes Shareable PDF ERJ-02554-2020.Shareable
T115 22001-22023 Sentence denotes Supplementary Material
T116 22024-22052 Sentence denotes ERJ-02554-2020.Shareable.pdf
T117 22054-22078 Sentence denotes Conflict of interest: D.
T118 22079-22195 Sentence denotes Armstrong-James reports grants and personal fees from Pulmocide Ltd and Gilead Sciences, outside the submitted work.
T119 22196-22220 Sentence denotes Conflict of interest: J.
T120 22221-22296 Sentence denotes Youngs reports funding from the UK and Ireland Gilead Fellowship Programme.
T121 22297-22321 Sentence denotes Conflict of interest: T.
T122 22322-22469 Sentence denotes Bicanic reports grants and personal fees for lectures from Gilead Sciences Ltd, personal fees for lectures from Pfizer, outside the submitted work.
T123 22470-22494 Sentence denotes Conflict of interest: A.
T124 22495-22592 Sentence denotes Abdolrasouli has received speaker honoraria from Gilead Sciences Ltd, outside the submitted work.
T125 22593-22619 Sentence denotes Conflict of interest: D.W.
T126 22620-22741 Sentence denotes Denning and family hold founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company; D.W.
T127 22742-22978 Sentence denotes Denning acts or has recently acted as a consultant to Scynexis, Pulmatrix, Pulmocide, Zambon, iCo Therapeutics, Mayne Pharma, Biosergen, and Fujifilm; and has been paid for talks on behalf of Hikma, Gilead, Merck, Mylan and Pfizer; D.W.
T128 22979-23191 Sentence denotes Denning is a longstanding member of the Infectious Disease Society of America Aspergillosis Guidelines group, the European Society for Clinical Microbiology and Infectious Diseases Aspergillosis Guidelines group.
T129 23192-23216 Sentence denotes Conflict of interest: E.
T130 23217-23249 Sentence denotes Johnson has nothing to disclose.
T131 23250-23274 Sentence denotes Conflict of interest: V.
T132 23275-23411 Sentence denotes Mehra reports personal fees for lectures from Pfizer, Novartis, Incyte and Gilead Sciences, grants from MSD, outside the submitted work.
T133 23412-23436 Sentence denotes Conflict of interest: T.
T134 23437-23548 Sentence denotes Pagliuca reports personal fees for advisory board work from Gilead, MSD and Pfizer, outside the submitted work.
T135 23549-23573 Sentence denotes Conflict of interest: B.
T136 23574-23604 Sentence denotes Patel has nothing to disclose.
T137 23605-23629 Sentence denotes Conflict of interest: J.
T138 23630-23661 Sentence denotes Rhodes has nothing to disclose.
T139 23662-23686 Sentence denotes Conflict of interest: S.
T140 23687-23791 Sentence denotes Schelenz reports personal fees for lectures from Gilead Sciences and Pfizer, outside the submitted work.
T141 23792-23816 Sentence denotes Conflict of interest: A.
T142 23817-23942 Sentence denotes Shah reports grant funding from Gilead Sciences and Vertex Pharmaceuticals, and speaker fees from Gilead Sciences and Pfizer.
T143 23943-24010 Sentence denotes Conflict of interest: F.L. van de Veerdonk has nothing to disclose.
T144 24011-24037 Sentence denotes Conflict of interest: P.E.
T145 24038-24297 Sentence denotes Verweij has received research grants from Gilead Sciences, F2G Ltd, Pfizer, Thermofisher and Merck, has served on an advisory board for Gilead Sciences, Mundipharma and F2G, and has received speaker honoraria from F2G, Mundipharma, Pfizer and Gilead Sciences.
T146 24298-24324 Sentence denotes Conflict of interest: P.L.
T147 24325-24429 Sentence denotes White reports personal fees from Gilead, Pfizer and F2G, grants from Bruker, outside the submitted work.
T148 24430-24456 Sentence denotes Conflict of interest: M.C.
T149 24457-24563 Sentence denotes Fisher reports grants and personal fees for lectures from Gilead Sciences Ltd, outside the submitted work.
T150 24564-24582 Sentence denotes Support statement:
T151 24583-24764 Sentence denotes This work was supported by the Natural Environment Research Council (grant NE/P001165/1), Medical Research Council (grant MR/R015600/1) and Canadian Institute for Advanced Research.
T152 24765-24855 Sentence denotes Funding information for this article has been deposited with the Crossref Funder Registry.