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

Abstract

I ncidence of coronavirus disease (COVID-19)associated pulmonary aspergillosis (CAPA) in hospital intensive care units (ICUs) is 3.8%-33.3% (1-9). Variations might be explained by differences in patient populations and CAPA defi nitions used, complicating direct comparisons between studies.Diagnosing CAPA is complex because cases frequently lack typical radiologic features and European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) host factors ( 10) and because mycologic evidence is diffi cult to obtain. Serum galactomannan (GM) detection has low sensitivity in CAPA (7,10).The European Confederation of Medical Mycology and International Society for Human and Animal Mycology (ECMM/ISHAM) published consensus criteria for a CAPA defi nition (11). We used these criteria to perform an observational cohort study to assess CAPA incidence in patients with COVID-19 admitted to ICUs during the fi rst wave of the COVID-19 pandemic. The StudyWe collected partially prospective and partially retrospective data for 823 patients in 2 cohorts. The discovery cohort comprised patients with PCR-confi rmed or clinically presumed COVID-19 admitted to 4 ICUs in the Netherlands and 4 ICUs in Belgium during February 28-May 27, 2020. The validation cohort comprised patients with PCR-confi rmed COVID-19 admitted because of respiratory insuffi ciency to 3 participating ICUs in France during April 7-May 31, 2020 (Appendix Methods, Table 1, https://wwwnc.cdc.gov/EID/ article/27/11/21-1174-App1.pdf).

A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA)

“…The middle date of inclusion is calculated as the date in the middle, between the start and end date of study inclusion. The partially retrospective/prospective study by Janssen et al [16] is counted as a retrospective study. CAPA incidence is calculated per study for the combination of proven, probable, putative and possible CAPA cases.…”

“…The maps on the right show the pooled CAPA incidence per country in studies with observational data. Only studies with exact information on the countries where patients were recruited were included in this figure [2,9,15,16,18,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][35][36][37][38]40,41,[43][44][45][47][48][49][51][52][53][54][55][56][57][58][59]. CAPA incidence is calculated per study for the combination of proven, probable, putative and possible CAPA cases.…”

“…CAPA is typically diagnosed approximately one week after ICU admission. The median time between ICU admission and the first positive mycological evidence was 6 days (IQR 3-9 days) in the largest observational study by Janssen et al [16]. Since most people with severe COVID-19 require ICU admission at approximately 10 days after symptom onset [64][65][66][67], CAPA occurs late during the COVID-19 disease course.…”

“…Reports on CAPA IATB are scarce, probably in part due to a reluctance to perform bronchoscopy in severe COVID-19 patients due to safety concerns (especially in the first wave of the pandemic) [68]. In the paper by Janssen et al, CAPA IATB was reported in 4 of 90 CAPA patients (4.4%) [16].…”

Managing secondary fungal infections in severe COVID-19: how to move forward?

“…However, primary prophylaxis depends on the anticipated frequency of secondary fungal infections. Although reported CAPA incidence is 10–17%, 4 , 6 , 7 most of these studies were performed during the first wave of COVID-19, whereas the current epidemiology is likely to have changed. Factors that might increase invasive fungal infection frequency include the standard use of dexamethasone combined with anti-IL-6 in severe COVID-19, emergence of new (more virulent) SARS-CoV-2 variants, 8 and a possible shift towards unvaccinated individuals and those who respond less well to vaccination.…”