Amplified inflammatory and immune responses in viral-associated pulmonary aspergillosis

Viral-associated pulmonary aspergillosis (VAPA) is a severe complication of viral pneumonia (VP) that is associated with pronounced inflammatory amplification, immune dysregulation, and increased mortality. However, systemic metabolic and immune response patterns accompanying VAPA remain incompletely understood.

Plasma samples were obtained from 35 patients with viral pneumonia (VP group) and 20 with viral-associated pulmonary aspergillosis (VAPA group). An integrated multi-omics strategy combining data-independent acquisition (DIA)-based proteomics and untargeted metabolomics was used. In total, 1,930 proteins and 1,532 metabolites were identified. Differential analyses along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to characterize host immune and metabolic alterations associated with viral-fungal coinfection.

Compared to patients with VP, those with VAPA showed more pronounced systemic inflammatory activity, immune dysregulation, hepatic and renal impairment, and coagulation abnormalities. Proteomic profiling revealed a higher abundance of proteins related to antioxidant responses, protein degradation pathways, and inflammatory and immune signaling in patients with VAPA. Metabolomic analyses indicated substantial alterations in lipid metabolism, increased oxidative stress-related metabolites, and dysregulation of hormone- and vitamin-associated metabolic pathways. Together, these proteomic and metabolomic patterns were associated with enhanced inflammatory burden, disrupted immune regulation, and greater disease severity.

This study provides a systematic overview of immune and metabolic alterations in patients with VAPA. The observed multi-omics features offer insights into host responses associated with viral-fungal coinfection and provide potential theoretical support for early identification and targeted intervention of VAPA.