COVID-19-associated pulmonary aspergillosis (CAPA) in Iranian patients admitted with severe COVID-19 pneumonia

Abstract

Purpose Bacterial or virus co-infections with SARS-CoV-2 have been reported in many studies; however, the knowledge on Aspergillus co-infection among patients with COVID-19 was limited. This study was conducted to identify and isolate fungal agents and to evaluate the prevalence of pulmonary aspergillosis (CAPA) as well as antifungal susceptibility patterns of Aspergillus species in patients with COVID-19 admitted to Shahid Beheshti Hospital, Kashan, Iran. Methods The study involved 119 patients with severe COVID-19 pneumonia referred to the Shahid Beheshti Hospital, Kashan, Iran. A total of 17 Aspergillus spp. that were isolated from COVID-19 patients suspected of CAPA were enrolled in the study. CAPA was defined using ECMM/ISHAM consensus criteria. The PCR amplification of the β-tubulin gene was used to identify the species. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B against Aspergillus spp. were evaluated according to the Clinical and Laboratory Standards Institute manual (M38-A3). Results From the 119 patients with severe COVID-19 pneumonia, CAPA was confirmed in 17 cases (14.3%). Of these, 12 (70.6%) were males and 5 (29.4%) were females; the mean age at presentation was 73.8 years (range: 45–88 years; median = 77; IQR = 18). Aspergillus fumigatus (9/17; 52.9%), Aspergillus flavus (5/17; 29.4%), Aspergillus oryzae (3/17, 17.6%), were identified as etiologic agents of CAPA, using the molecular techniques. Voriconazole and amphotericin B showed more activity against all isolates. Moreover, the MIC of fluconazole, itraconazole varied with the tested isolates. For 3 clinical isolates of A. fumigatus, 2 isolate of A. flavus and 3 A. oryzae , the MIC of fluconazole and itraconazole were ≥ 16 µg/mL. Conclusions We observed a high incidence (14.3%) of probable aspergillosis in 119 patients with COVID-19, which might indicate the risk for developing IPA in COVID-19 patients. When comparing patients with and without CAPA regarding baseline characteristics, CAPA patients were older ( p =0 .024), had received more frequent systemic corticosteroids ( p = 0.024), and had a higher mortality rate ( p = 0.018). The outcome of CAPA is usually poor, thus emphasis shall be given to screening and/or prophylaxis in COVID-19 patients with any risk of developing CAPA.

A nomogram model in invasive pulmonary aspergillosis diagnosis based on a retrospective study

“…But it was found that 32.6% had poor clinical outcomes in our study.Multivariate analysis revealed that advanced age, mechanical ventilation, use of corticosteroids and IPA were independent risk factors for mortality in patients with positive Aspergillus respiratory tract cultures. This is consistent with previous literature [2,9,10] . Moreover, antifungal therapy was a protective factor.Although there was no significant difference n when to initiate antifungal treatment, a trend suggested that the early use of antifungal drugs could improve clinical outcomes to some extent.…”

COVID-19-Associated Pulmonary Aspergillosis Isolates Are Genomically Diverse but Similar to Each Other in Their Responses to Infection-Relevant Stresses

“…A limitation of this study is the small number of isolates included and the absence of any A. fumigatus isolate resistant to antifungal drugs. However, other studies have reported the recovery of azole-resistant isolates in patients with CAPA, thus supporting the clinical value of antifungal susceptibility testing in these patients ( 32 to 34 ). In addition, point mutations in the azole target enzyme in A. fumigatus 14-α sterol demethylase ( Cyp51A ) have been recently described in patients with CAPA; these include the TR34/L98H alteration in the promoter region and G54RF46Y, M172V, and E427K ( 33 ).…”

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

“…Thus, 21 cohort studies were eligible and were included in the meta-analysis. 3,4,[27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] The PRISMA flow chart depicting the literature search and selection of eligible studies is shown in Fig. 1.…”