The risk for developing COVID-19-associated pulmonary aspergillosis (CAPA) is increased by treatment with glucocorticoids (GC) and exacerbated with use of high-dose glucocorticoids (GC) or dexamethasone treatment, according to systematic review and meta-analysis findings published in Mycoses.
Investigators sought to assess whether the development of CAPA is associated with systemic GC treatment in patients with COVID-19.
Researchers conducted a systematic review and meta-analysis of controlled studies published in peer-reviewed journals reporting on CAPA in adult patients hospitalized with COVID-19 and treated with GC. The reviewers searched Google Scholar, Scopus, Embase, and PubMed databases for studies published in English from inception through December 2022. Studies lacking a standard definition of CAPA were excluded.
Investigators included 20 studies from Europe, Asia, and North America (N=4675) with 2565 patients treated with GC and without any other immunomodulators and 2110 patients (control group) treated without GC or other immunomodulators. Included studies were of high quality; there was no publication bias, but there was heterogeneity (I2=46.61%).
Investigators found the pooled log odds ratio (LOR) of CAPA development for the GC group was significantly higher than for the control group (0.54; 95% CI, 0.22-0.86; P <.01).
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GC therapy independent of other (immunomodulator) treatments increases the risk of CAPA development, and this risk is significantly associated with the use of high-dose GC or dexamethasone treatment.
In subgroup analysis of patients in the intervention vs control groups, pooled LOR showed no significant difference for low-dose GC (0.41; 95% CI, -0.07 to 0.89; P =.09) or for non-dexamethasone GC intervention (0.21; 95% CI, -0.36 to 0.79; P =.47). In contrast, pooled LOR was higher for high-dose GC (0.90; 95% CI, 0.17-1.62; P =.01) and for dexamethasone (0.71; 95% CI, 0.35-1.07; P <.01).
Investigators noted 16 of the 20 studies used the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) consensus criteria to define CAPA; of those 16 studies, 13 used these criteria alone whereas 3 studies used these criteria along with additional definitions involving practice guideline criteria. Sub-analysis of these 16 studies showed similar significant association between GC treatment and risk of CAPA.
This meta-analysis was limited in that most included studies were retrospective and observational and may have had confounding factors. Other limitations were heterogeneity, including variation in the definition of CAPA, and limited data on low and high doses of dexamethasone and non-dexamethasone GC.
“GC therapy independent of other (immunomodulator) treatments increases the risk of CAPA development, and this risk is significantly associated with the use of high-dose GC or dexamethasone treatment,” investigators concluded. They added, “Further clinical evidence from high-quality and large-sized studies with additional clinical variables may be needed to generalize and validate the implications of this meta-analysis for clinical practice.”
