Mapping Longitudinal Lung Mycobiome Characteristics of Severe COVID-19 patients, a prospective, multicenter cohort study

Wenxiao Zhang ¹, Chen Peng ², Silan Gu ³, Xiaonan Su ⁴, Guojun He ⁵, Yijiao Han ⁵, Chunfeng He ⁵, Liang Zhang ⁵, Mingqiang Wang ¹, Lin Zhong ⁶, Lingtong Huang ⁵, Chao Jiang ^2 3 5

Abstract

Understanding the longitudinal dynamics of the lung mycobiome in severe COVID-19 is crucial given the link between viral infection and fungal complications. This prospective, multicenter cohort study tracked respiratory and gut fungal communities in critically ill COVID-19 patients using internal transcribed spacer sequencing and digital droplet PCR. We observed that while the respiratory mycobiome remained stable early after ICU admission, significant alterations occurred during prolonged mechanical ventilation. Although antifungal therapy influenced fungal composition, it did not correlate with survival. Notably, combining lung mycobiome signatures with clinical variables significantly improved mortality prediction, whereas the gut mycobiome showed weak prognostic association. These findings indicate that respiratory fungal dynamics are more closely tied to clinical outcomes than those of the gut in our cohort, suggesting that integrating lung mycobiome profiling could enhance prognostic stratification and management strategies for severe COVID-19.