%0 Journal Article
%T Defining COVID-19-associated pulmonary aspergillosis: systematic review and meta-analysis.
%A Kariyawasam RM
%A Dingle TC
%A Kula BE
%A Vandermeer B
%A Sligl WI
%A Schwartz IS
%J Clin Microbiol Infect
%V 28
%N 7
%D Jul 2022
%M 35150878
%F 13.31
%R 10.1016/j.cmi.2022.01.027
%X <B>BACKGROUND: </B>Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies.<BR><B>OBJECTIVE: </B>We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions.<BR><B>METHODS: </B>PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021.<BR><B>METHODS: </B>ICU cohort studies and CAPA case series including ≥3 patients were included.<BR><B>METHODS: </B>Adult patients in ICUs with COVID-19.<BR><B>METHODS: </B>Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews.<BR><B>METHODS: </B>We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis.<BR><B>RESULTS: </B>Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival.<BR><B>CONCLUSIONS: </B>The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.