Publication date: Aug 15, 2025

Modern society faces a variety of respiratory-related threats from the increased use of chemicals and periodic outbreaks of infectious diseases. This study investigates the connection between chemically-induced lung damage and SARS-CoV-2 infection, addressing a critical research gap. To investigate this connection, we conducted a study using a mouse model to assess SARS-CoV-2 infection symptoms in lungs injured by polyhexamethylene guanidine phosphate (PHMG-p). Our research revealed that PHMG-p-Induced Lung Injury (PILI) mice exhibited severe inflammatory responses and lung damage following infection. Cytokine storm-related factors were significantly elevated in the bronchoalveolar lavage fluids of infected PILI mice, indicating severe infection. RNA-seq analysis showed upregulated genes in infected PILI mice associated with respiratory tract diseases and increased inflammatory and immune responses. Downregulated genes were primarily involved in lipid metabolism processes. We also identified alterations in four _genes linked to asthma development in infected PILI mice, correlating with clinical observations in patients. Our findings suggest that SARS-CoV-2 infection in chemically damaged lungs may exacerbate symptoms and potentially lead to new-onset asthma. This study highlights the increased risk of infection severity in chemically damaged lungs and emphasizes the need for heightened awareness of respiratory health in individuals exposed to chemicals, especially during infectious disease outbreaks.

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