Table 2.
Studies Describing Coronavirus Disease 2019 (COVID-19)–Associated Pulmonary Aspergillosis in Critical Care COVID-19 Patients
| Reference | Study Design | Case/Total (%) | Certainty of Diagnosisa | Comments |
|---|---|---|---|---|
| Koehler et al [38] | Case series | 5/19 (26.3) | 4/5 | One pt Aspergillus fumigatus detected in TA only |
| Van Arkel et al [40] | Case series | 6/31 (19.4) | 3/6 | One pt A fumigatus detected in TA, serum GMI: 0.4; one pt A fumigatus detected in TA only; and one pt A fumigatus detected in sputum only |
| Zhu et al [42] | Prospective cohort | 5/17 (29.4) | Unclear | Details not provided |
| Du et al [43] | Case series | 3/9 (33.3) | 0/3 | All patients positive in sputum |
| Chen et al [44] | Case series | 6/17 (35.3) | Unclear | Culture of various respiratory samples, details not provided |
| Machado et al [41] | Prospective cohort | 8/239 (3.3) | 7/8 | Cases classified using EORTC/MSGERC and ASPICU definitions; 9 additional pts deemed to be colonized. One pt A fumigatus detected in TA |
| Bartoletti et al [9] | Prospective cohort | 30/108 (27.8) | 30/30 | All cases had BAL GMI ≥1.0 |
| Nasir et al [45] | Retrospective cohort | 5/23 (21.7) | Unclear | 4 additional pts deemed to be colonized |
| Rutsaert et al [46] | Case series | 7/34 (20.6) | 6/7 | One pt Aspergillus flavus detected in TA |
| Alanio et al [39] | Case series | 9/27 (33.3) | 8/9 | One pt BAL GMI <1.0 |
| Helleberg et al [47] | Case series | 2/8 (25.0) | 1/2 | One pt A fumigatus detected in TA |
| Dupont et al [48] | Prospective cohort | 19/106 (17.9) | 15/19 | Four pts A fumigatus detected in TA |
| Segrelles-Calvo et al [49] | Prospective cohort | 7/215 (3.2) | 8/9 | One pt had Aspergillus sp detected in sputum |
| Borman et al [50] | Prospective samplesb | Proven/probable 36/719 (5.0)
Possible 108/719 (15.0) |
Unclear | Pts classified using modified ASPICU definitions |
| Van Biesen et al [51] | Case series | 9/42 (21.4) | 9/9 | Nondirected bronchial lavage testing |
| Wang et al [52] | Retrospective cohort | 8/104 (7.7) | 4/8 | Cases classified using the EORTC/MSGERC definitions. Four pts had Aspergillus sp detected in sputum |
| Flikweert et al [19] | Case series | 6/7 | 6/6 | Compares histology where 0/6 had evidence of IPA |
| White et al [11] | Prospective cohort | 19/135 (14.1) | 13/19 | BDG testing incorporated into diagnostic strategy. Patients defined using local definitions |
| Delliere et al [53] | Retrospective cohort | 21/108 (19.4) | Unclear | Cases classified using the EORTC/MSGERC definitions and revised IAPA definitions |
| Lamoth et al [54] | Prospective cohort | 3/80 (3.8) | 3/3 | Cases classified using modified IAPA definitions |
| Gangneux et al [55] | Prospective cohort | 7/45 (15.6) | Unclear | Cases classified using modified ASPICU definitions |
| Gouzien et al [56] | Retrospective cohort | 2/53 (3.8) | 2/2 | One pt Aspergillus detected in TA. Limited testing of respiratory samples |
| Ripa et al [57] | Prospective cohort | 10/86 (11.6)c | 10/10 | Includes secondary infections in all COVID-19 patients |
| Brown et al [58] | Prospective cohort | 2/62 (3.2) | 0/2 | One patient meets EORTC/MSGERC classification |
| Ichai et al [59] | Case series | 6/26 (23.1) | Unclear | Link with negative pressure rooms and CAPA, 2 further patients colonized with Aspergillus |
| Maes et al [60] | Retrospective cohort | 3/23 (13.0) | 3/3 | IAPA classifications modified to include PCR |
| Razazi et al [61] | Retrospective cohort | 7/90 (7.8) | 7/7 | Updated IAPA classification used |
| IPA in COVID-19 less than non–COVID-19 pts | ||||
| Meijer et al [62] | Case series | 13/66 (19.7) | 13/13 | ECMM/ISHAM classification used. Data for both waves of the pandemic |
| Yusuf et al [63] | Case-control study | 5/92 (5.4) | 5/5 | Comparison with IPA in influenza and bacterial infection |
| Fekkar et al [18] | Retrospective cohort | 6/145 (4.1) | 4/6 | Used EORTC/MSGERC classification or negativity in follow-up testing in the absence of clinical deterioration or survival without antifungal treatment to classify CAPA |
| Versyck et al [64] | Retrospective cohort | 2/54 (3.7) | 2/2 | Modified ASPICU definitions |
| Roman-Montes et al [65] | Prospective cohort | 14/144 (9.7) | 6/14 | Modified ASPICU definitions, TA testing with GM-EIA and LFA |
| Van Grootveld et al [66] | Prospective cohort | 11/63 (17.5) | 11/11 | Four additional patients considered colonized. Compares TA and BAL testing |
| Chauvet et al [10] | Retrospective cohort | 6/46 | 3/6 | Used EORTC/MSGERC, ASPICU, and modified ASPICU definitions |
| Heard et al [67] | Retrospective cohort | 1/57 | 0/1 | Highlights issues with empirical antifungal therapy |
| Permpalung et al [8] | Retrospective cohort | 39/396 | 12/39 | BDG testing incorporated into diagnostic strategy. Definitions based on proposed classifications and a local definition of possible CAPA |
| Total | 353d/3519 | 195/273 | ||
Abbreviations: ASPICU, Aspergillus in the Intensive Care Unit; BAL, bronchoalveolar lavage; BDG, (1–3)-β-D-glucan; CAPA, coronavirus disease 2019–associated pulmonary aspergillosis; COVID-19, coronavirus disease 2019; ECMM/ISHAM, European Confederation of Medical Mycology and International Society for Human and Animal Mycology; EORTC/MSGERC, European Organization for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium; GM-EIA, galactomannan enzyme immunoassay; GMI, galactomannan index; IAPA, influenza-associated pulmonary aspergillosis; IPA, invasive pulmonary aspergillosis; LFA, lateral flow assay; pt, patient; TA, tracheal aspirate.
Meets ECMM/ISHAM definition of CAPA. Includes proven, probable, and possible CAPA, where possible CAPA permits nondirected bronchial lavage testing. For the purpose of this table, bronchial aspirates have been included, whereas sputum and tracheal aspirates are considered inadequate evidence.
Samples referred from multiple centers to a specialist national mycology reference facility for testing.
Intensive care unit patients only.
Excludes 108 possible cases defined by Borman et al.