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Volume 27, Number 11—November 2021
Dispatch

Multinational Observational Cohort Study of COVID-19–Associated Pulmonary Aspergillosis1

Nico A.F. Janssen, Rémy Nyga, Lore Vanderbeke, Cato Jacobs, Mehmet Ergün, Jochem B. Buil, Karin van Dijk, Josje Altenburg, Catherine S.C. Bouman, Hans I. van der Spoel, Bart J.A. Rijnders, Albert Dunbar, Jeroen A. Schouten, Katrien Lagrou, Marc Bourgeois, Marijke Reynders, Niels van Regenmortel, Lynn Rutsaert, Piet Lormans, Simon Feys, Yves Debavaye, Fabienne Tamion, Damien Costa, Julien Maizel, Hervé Dupont, Taieb Chouaki, Saad Nseir, Boualem Sendid, Roger J.M. Brüggemann, Frank L. van de Veerdonk, Joost Wauters2, and Paul E. Verweij2Comments to Author 
Author affiliations: Radboud University Medical Center, Nijmegen, the Netherlands (N.A.F Janssen, M. Ergün, J.B. Buil, J.A. Schouten, R.J.M. Brüggemann, F.L. van de Veerdonk, P.E. Verweij); Amiens University Hospital, Amiens, France (R. Nyga, J. Maizel, H. Dupont, T. Chouaki); University Hospitals Leuven, Leuven, Belgium (L. Vanderbeke, C. Jacobs, K. Lagrou, Y. Debavaye, J. Wauters); Katholieke Universiteit Leuven, Leuven (L. Vanderbeke, K. Lagrou, J. Wauters); Amsterdam University Medical Centers, Amsterdam, the Netherlands (K. van Dijk, J. Altenburg, C.S.C. Bouman, H. van der Spoel); Erasmus Medical Center, Rotterdam, the Netherlands (B.J.A. Rijnders, A. Dunbar); AZ Sint-Jan Brugge-Oostende, Brugge, Belgium (M. Bourgeois, M. Reynders); ZNA Campus Stuivenberg, Antwerpen, Belgium (N. van Regenmortel, L. Rutsaert); AZ Delta Hospital, Roeselare, Belgium (P. Lormans, S. Feys); Rouen University Hospital, Rouen, France (F. Tamion, D. Costa); Lille University Hospital, Lille, France (S. Nseir, B. Sendid); University of Lille, Lille (S. Nseir, B. Sendid)

Main Article

Table 1

Demographic, clinical, and mycological characteristics of the discovery cohort in a multinational observational study of COVID-19–associated pulmonary aspergillosis in 3 countries in Europe, 2020*

Characteristics Total population, n = 519 CAPA, n = 42 CAPA excluded, n = 237 p value
Age, y
 64 (55–72)
 68 (61–73)
 65 (57–71)
 0.12
Sex
F 141 (27) 8 (19) 58 (24)
M
 378 (73)
 34 (81)
 179 (76)
 0.56
BMI, kg/m2
 27.2 (24.4–31.0); n = 507
 27.4 (23.6–30.2); n = 40
 26.9 (24.4–30.9); n = 231
 0.72
Underlying conditions
Cardiovascular disease† 291 (56) 25 (60) 130 (55) 0.62
Diabetes mellitus 139 (27) 9 (21) 61 (26) 0.70
Asthma 37 (7) 1 (2) 19 (8) 0.33
COPD 44 (9) 8 (19) 19 (8) 0.042
Liver cirrhosis 6 (1) 0 2 (0.8) 1.00
Rheumatological disease 31 (6) 5 (12) 14 (6) 0.18
HIV/AIDS 6 (1) 3 (7) 1 (0.4) 0.011
Solid organ malignancy
 28 (5)
 3 (7)
 11 (5)
 0.45
EORTC/MSGERC host factors
Any‡ 70 (16); n = 426 13 (33); n = 39 31 (19); n = 166 0.053
Recent neutropenia§ 7 (2); n = 413 1 (3); n = 38 5 (3); n = 156 1.00
Hematologic malignancy 18 (4) 4 (10) 9 (4) 0.11
Receipt of allogeneic SCT 4 (0.8); n = 516 0 3 (1); n = 236 1.00
Receipt of SOT 6 (1) 1 (2) 2 (0.8) 0.39
Systemic corticosteroids <30 d before
ICU admission, any dose 38 (9); n = 430 7 (18); n = 39 14 (9); n = 160 0.14
T or B cell immunosuppressants other 
than corticosteroids <90 d before ICU 
admission 31 (6); n = 514 7 (17) 12 (5); n = 233 0.014
Inherited severe immunodeficiency
 0; n = 517
 0
 0; n = 236
 NA
ICU treatment data
Invasive mechanical ventilation 423 (82); n = 517 40 (98); n = 41 225 (95) 0.70
No. invasive ventilation days¶ 14 (9–24); n = 395 16 (13–27); n = 37 18 (11–30); n = 212 0.98
RRT during ICU admission 93 (18); n = 516 17 (41) 44 (19); n = 236 0.004
Systemic corticosteroids during ICU 
admission
 216 (42); n = 516
 20 (48)
 131 (56); n = 236
 0.40
Outcome data
ICU death 154 (30); n = 518 22 (52) 81 (34) 0.036
ICU LOS, d#
 14 (8–24); n = 491
 18 (12–27); n = 39
 20 (12–32); n = 222
 0.84
Mycologic diagnostic tests
Serum GM OD >0.5, no. positive (%); 
no. values reported/no. performed 3 (2); 134/176 3 (11); 28/28 0; 106/148 NA
Serum GM OD** 0.10 (0.10–0.10); n = 134 0.10 (0.06–0.14); n = 28 0.10 (0.10–0.10); n = 106 0.95
Positive BALF/BL culture 17 (10); n = 166 17 (42); n = 41 0; n = 125 NA
BALF/BL GM OD >1.0, no. positive 
(%); no. OD values reported/no. 
BL/BALF performed 32 (19); 90/166 32 (78); 34/41 0; 55/125 NA
BALF/BL GM OD** 0.20 (0.10–1.50); n = 90 1.80 (1.00–3.90); n = 35 0.10 (0.10–0.20); n = 55 <0.001
Positive BALF/BL PCR, any Ct, no. 
positive (%); no. reported/no. tested
 9 (5); 11/166
 7 (17); 7/41
 2 (2); 4/125††
 NA
Days between ICU admission and first positive mycologic test‡‡ NA 6 (3–9); n = 41 NA NA

*Data are presented as no. (%) or median (IQR) unless otherwise indicated. Continuous variables were compared by Mann-Whitney U test, categorical variables by Fisher exact test with omission of missing data, unless stated otherwise. Total percentages might not equal 100% because of rounding. Bold text indicates statistical significance. BAL, bronchoalveolar lavage; BALF, BAL fluid; BL, bronchial lavage; BMI, body mass index; CAPA, COVID-19–associated pulmonary aspergillosis; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease; Ct, cycle threshold; CT, computed tomography; ECMO, extracorporeal membrane oxygenation; EORTC/MSGERC, European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium; GM, galactomannan; ICU, intensive care unit; IQR, interquartile range; LOS, length of stay; NA, not applicable; NBL, nonbronchoscopic lavage; OD, optical density; RRT, renal replacement therapy; SCT, stem cell transplantation; SOT, solid organ transplant. †Includes hypertension ‡Includes any use of systemic corticosteroids before ICU admission; If data on one or more EORTC host factors were missing, then data were regarded as missing for this variable. §Neutropenia includes absolute neutrophil count of <0.5 × 109 cells/L for >10 d. ¶If transferred to another hospital from ICU and still on ventilatory support of any kind, duration of invasive mechanical ventilatory support was regarded as missing data and not included in the analyses. The same holds true for those who received a tracheostomy for a prolonged weaning trajectory. #Data on ICU LOS were regarded as missing if transfer to another hospital was the reason for ICU discharge because exact ICU LOS was unknown. **When multiple values were reported for 1 patient, the median of these values was used for further calculations. ††Positive PCR with Ct values >36 as only positive mycologic criterion. ‡‡Mycologic test considered a criterion for proven, probable, or possible CAPA according to the 2020 European Confederation for Medical Mycology/International Society for Human and Animal Mycology classification (11).

Main Article

1The results of this study were presented at the Scientific Spring Meeting of the Dutch Society of Medical Microbiology (NVMM) and the Royal Dutch Society of Microbiology (KNVM), held online March 30–31, 2021; and at the 31st European Congress of Clinical Microbiology & Infectious Diseases (ECCMID), held online from July 9–12, 2021.

2These authors were co–principal investigators.

Page created: August 24, 2021
Page updated: October 19, 2021
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