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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 2

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

Characteristics Total population, n = 304 CAPA, n = 21 CAPA excluded, n = 188 p value
Age, y
 63 (55–71)
 67 (59–75)
 62 (53–69)
 0.06
Sex
F 227 (75) 21 (100) 141 (75)
M
 77 (25)
 0
 47 (25)
 0.005
BMI, kg/m2
 30.0 (26.0–34.4); n = 296
 30.2 (26.1–32.8); n = 20
 30.0 (26.4–34.5); n = 185
 0.84
Underlying conditions
Active hematologic malignancy 10 (3) 0 6 (3) 1.00
Cardiovascular disease† 185 (61) 17 (81) 112 (60) 0.06
Diabetes mellitus 92 (30) 9 (43) 62 (33) 0.47
Asthma 22 (7) 2 (10) 12 (6) 0.64
COPD 20 (7) 2 (10) 12 (6) 0.64
Liver cirrhosis‡ 5 (2) 2 (10) 2 (1) 0.051
Autoimmune disease 16 (5) 2 (10) 11 (6) 0.63
HIV/AIDS 3 (1) 0 1 (0.5) 1.00
Active solid organ malignancy 4 (1) 1 (5) 3 (2) 0.35
Bronchiectasis
 5 (2)
 2 (10)
 1 (0.5)
 0.027
EORTC/MSGERC host factors
Any§ 35 (12) 3 (14) 20 (11) 0.71
Recent neutropenia¶ 0; n = 303 0 0; n = 187 NA
Hematological malignancy 10 (3) 0 6 (3) 1.00
Receipt of SOT 9 (3) 1 (5) 5 (3) 0.48
Corticosteroids >0.3 mg/kg for 
>3 wks within previous 60 d 17 (6) 2 (10) 10 (5) 0.34
Other immunosuppressants 
<90 d before ICU admission
 23 (8)
 2 (10)
 16 (9)
 0.70
ICU treatment data
Invasive mechanical ventilation 228 (76); n = 302 19 (95); n = 20 168 (89) 0.70
No. invasive ventilation days 15 (9–25); n = 212 18 (13–25); n = 17 15 (9–25); n = 157 0.21
RRT 64 (21); n = 303 11 (55); n = 20 47 (25) 0.008
Systemic corticosteroids during 
ICU admission
 147 (49); n = 303
 11 (52)
 106 (57); n = 187
 0.82
Outcome data
ICU death 69 (23); n = 299 9 (43) 46 (25); n = 185 0.12
ICU LOS, d#
14 (8–26); n = 295
 22 (12–35); n = 20
 18 (10–28); n = 183
 0.27
Mycologic diagnostic tests
Serum GM OD >0.5 4 (2); n = 172** 4 (22); n = 18 0; n = 154†† NA
Serum GM OD 0.07 (0.04–0.12); n = 172** 0.10 (0.06–0.34); n = 18 0.06 (0.04–0.11); n = 154†† 0.008
Positive BALF culture 11 (8); n = 135 11 (52) n = 21 0; n = 114 NA
BALF GM OD >1.0 13 (11); n = 123 13 (62) n = 21 0; n = 102 NA
BALF GM OD‡‡
 0.12 (0.05–0.32); n = 123
 1.10 (0.12–3.06); n = 21
 0.11 (0.05–0.18); n = 102
 <0.001
Positive BALF PCR, any Ct 8 (13); n = 64 8 (53); n = 15 0; n = 49 NA
Serum β-D-glucan value 
≥80 pg/mL 37 (20); n = 184 8 (42); n = 19 29 (18); n = 160 0.030
Serum β-D-glucan value§§ 31 (13–60); n = 184 34 (31–156); n = 19 31 (10–59); n = 160 0.055

*Data are presented as no. (%) or median (IQR), unless stated otherwise. 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; ICU, intensive care unit; IQR, interquartile range; GM, galactomannan; LOS, length of stay; NA, not applicable; OD, optical density; RRT, renal replacement therapy; SAPS, simplified acute physiology score; SOT, solid organ transplant; TBA, tracheobronchial aspirate. †Includes Factor V Leiden mutation and hypertension. ‡Includes hemochromatosis. §Includes use of any systemic corticosteroids. We did not assess receipt of an allogeneic stem cell transplant, presence of an inherited severe immunodeficiency, and presence of acute graft-versus-host disease. ¶Neutropenia includes absolute neutrophil count of <0.5 × 109/L for >10 d. #Data on ICU LOS were regarded as missing if still admitted at the time of data entry or if transfer to another hospital was the reason for ICU discharge. **Serum GM performed in 173 patients, including 1 patient with an unknown result. ††Serum GM values known for 154 patients, unknown value in 1 patient. ‡‡One value of >6.0 entered as 6.0. §§One value of >500 pg/mL entered as 500 pg/mL.

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.

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Page updated: October 19, 2021
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