TABLE 1 Summary of reported cases of coronavirus disease 2019 (COVID-19) associated pulmonary aspergillosis in the intensive care unit (ICU) setting
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Antwerp, Belgium [8] 38 M None (+) A. fumigatus NR (+) >2.8 (-) Histology from bronchoscopy (+) 6 Proven Proven V, I Alive
Antwerp, Belgium [8] 62 M Diabetes ND A. fumigatus NR (+) >2.0 (-) Histology from bronchoscopy (+) 16 Proven Proven V Died
Antwerp, Belgium [8] 73 M Diabetes ND A. fumigatus NR (+) >2.8 (-) Histology from bronchoscopy (+) 5 Proven Proven V Alive
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
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
Antwerp, Belgium [8] 75 M AML with IPA 2012 ND A. fumigatus NR (+) 2.63 ND 8 No host factor Putative V Died
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
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
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
Breda, The Netherlands [10] 43 M None NR (-) NR (+) 3.8 (-) 14 No host factor Putative V+A, or L-AmB Alive
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
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
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
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. 9 Proven Proven L-AmB Died
Summary Median (IQR)70 (57–75) M: 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
IPA: invasive pulmonary aspergillosis; BAL: bronchoalveolar lavage; TA: tracheal aspirate; GM: galactomannan; EORTC: 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: 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.