Diagnosis of invasive pulmonary aspergillosis using metagenomic next-generation sequencing and conventional microbial tests post-COVID-19 pandemic

ABSTRACT Early recognition and timely diagnosis are crucial for improving the clinical outcome of invasive pulmonary aspergillosis (IPA) patients. Metagenomic next-generation sequencing (mNGS) shows immense advantages in identifying responsible complex pathogens, especially with the gradual ease of COVID-19 control policies in China since 2022. A total of 327 patients with suspected Aspergillus infection in non-neutropenic populations were enrolled in the current study. The diagnostic efficacy with mNGS and conventional microbial tests (CMTs) in suspected IPA patients was assessed, and the incidence and risk factors for Aspergillus infection were also investigated. mNGS exhibited excellent performance in detecting Aspergillus . The sensitivity of mNGS (80.58%) was superior to that of CMTs, as demonstrated by comparisons with smears (22.30%, P < 0.001), culture (30.94%, P < 0.001), serum GM (22.62%, P < 0.001), BALF GM (55.40%, P < 0.001), and combined CMTs (61.87%, P < 0.001). The results of mNGS caused a direct shift in the management of 212 (64.8%) positive effect patients, making a clear diagnosis and instructing antifungal therapy. Notably, in addition to the common risk factors, the patients with a history of COVID-19 infection were more prone to IPA. The occurrence of IPA increased significantly with the gradual ease of COVID-19 control policies (47.62% vs 30.21%, P = 0.004). Meanwhile, mixed infections were commonly observed in IPA patients, with Human gammaherpesvirus and Acinetobacter baumannii being the most common co-pathogens. Our study demonstrated that mNGS might present a feasible and remarkably sensitive approach for detecting Aspergillus , thereby serving as a valuable auxiliary tool for CMTs. IMPORTANCE Our study is the first to focus on Aspergillus infection after the COVID-19 pandemic and find that (i) mNGS is a feasible and highly sensitive method for detecting Aspergillus post-COVID-19 pandemic, thereby serving as a valuable auxiliary tool for CMTs. (ii) mNGS has the potential to revolutionize the management of fungal infections. (iii) The history of COVID-19 infection is an independent risk factor for IPA. Identification of this risk factor for IPA may raise clinical attention and require careful follow-up of high-risk individuals post-COVID-19 infection. (iv) Mixed infections were commonly observed in IPA patients, with Human gammaherpesvirus and Acinetobacter baumannii being the most common co-pathogens.