Clin Microbiol Infect. 2022 Feb 9:S1198-743X(22)00051-9. doi: 10.1016/j.cmi.2022.01.027. Online ahead of print.
BACKGROUND: Pulmonary aspergillosis may complicate 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.
OBJECTIVES: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions.
DATA SOURCES: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021.
STUDY ELIGIBILITY CRITERIA: ICU cohort studies and CAPA case series including ≥3 patients were included.
PARTICIPANTS: Adult patients in ICUs with COVID-19.
DEFINITIONS: Patients were reclassified according to 4 research definitions (respectively described by Verweij et al, White et al, Koehler et al, and Bassetti et al).
ASSESSMENT OF RISK OF BIAS: We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews.
METHODS OF DATA SYNTHESIS: We calculated CAPA prevalence using 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.
RESULTS: 51 studies were included. Among 3,297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%, 95% confidence interval 8-13%). 277 patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ=0.268 to 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.
CONCLUSIONS: The reported prevalence of CAPA is significant, but may be exaggerated by non-standard definitions.