Effect of Glucocorticoids on the Development of COVID-19-Associated Pulmonary Aspergillosis: A Meta-Analysis of 21 Studies and 4972 Patients

Background: The COVID-19-associated pulmonary aspergillosis (CAPA) remains a global cause of high mortality throughout the pandemic, but its root cause is still obscure. Our aim was to systematically synthesize the effect of glucocorticoids (GCs) on the development of CAPA.Methods: We conducted a meta-analysis by systematically searching the PubMed/MEDLINE, Google Scholar, Scopus, and Embase databases and citations to collect eligible studies published until October 10, 2022. The eligibility criteria included full-text English language cohort studies reporting CAPA in patients treated with GC or no GC (No-GC) therapy. The outcome measure of the study was the development of CAPA in GC-treated patients. The pooled outcome was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. Publication bias, heterogeneity and quality were assessed using standard methods. The PROSPERO registration-ID of the study was CRD42022341633.Findings: Our database search identified a total of 2256 studies, of which 21 studies with 4972 patients met the eligibility criteria and were included in the meta-analysis. The GC vs No-GC therapy had a higher pooled LOR of the outcome [0.85 (95% CI: 0.44 to 1.26), Z=4.07, p=0.00]. The pooled LOR of high- vs low-dose GC had no difference [0.64 (95% CI: -0.08 to 1.35, Z=1.75; p=0.08), but it was higher for low-dose GC [0.71 (95% CI: 0.16 to 1.26, Z=2.55, p=0.01) and high-dose GC [0.92 (95% CI: 0.30 to 1.53), Z=2.94; p=0.00] as compared to No-GC therapy. The pooled LOR was higher for dexamethasone [0.80 (95% CI: 0.29 to 1.31), Z=3.09, p= 0.00], and prednisolone [1.28 (95% CI: 0.23 to 2.32), (z=2.39, p=0.02] but had no difference for methylprednisolone [0.44 (95% CI: -0.43 to 1.30), z =0.99, p=0.32] as compared to No-GC therapy. The studies were of high quality but had publication bias and heterogeneity.Interpretation: The GC therapy of COVID-19 increases the risk of CAPA development and this risk is more with high-dose as compared to low-dose therapy. Among common GC types, methylprednisolone therapy has no or minimal risk of CAPA. Our data collectively suggest the use of low-to-moderate doses of methylprednisolone as GC therapy of choice for COVID-19 to minimize or prevent the risk of CAPA development and improve the outcome of the disease.Funding: None.Declaration of Interests: The authors declare that there are no conflicts of interest.