Insights into dysregulated innate immunity in the pathogenesis of COVID-19-associated pulmonary aspergillosis

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a severe complication arising from the co-infection of viral and fungal pathogens in the lungs, with its incidence notably increasing. Although significant progress has been made in elucidating the pathogenesis of CAPA in recent years, the precise pathophysiological mechanisms underlying this condition remain only partially understood. Current evidence indicates that CAPA primarily results from dysregulation of innate antifungal immune responses. Key contributing factors include epithelial barrier dysfunction, impaired phagocytic activity against fungi, aberrant expression of antimicrobial peptides, immunologic tolerance, and lung dysbiosis, all of which collectively weaken host defense mechanisms. Concurrently, excessive pro-inflammatory responses-driven by cytokine storms and oxidative stress associated with antiviral immunity-further exacerbate lung injury in COVID-19 patients, creating a detrimental feedback loop that impairs immune function and heightens susceptibility to CAPA. In this review, we summarize and discuss recent advances in understanding the role of dysregulated innate immunity in the pathogenesis of CAPA. These insights may inform clinical management strategies and improve outcomes for patients suffering CAPA.