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Protective Effect of Indole-3-Aldehyde in Murine COVID-19-Associated Pulmonary Aspergillosis
Marilena Pariano1, Anna Gidari1, Claudia Stincardini1
1Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
Abstract:
Aspergillus fumigatus is an environmental fungus recently included in the fungal high-priority pathogens by the World Health Organization. While immunodeficiency and/or pre-existing lung damage represent a well-recognized fertile ground for fungal growth, it is increasingly being recognized that severe viral infections may similarly favor A. fumigatus colonization and infection, as recently experienced in the Coronavirus disease 2019 (COVID-19) pandemic. Herein, in a murine model of COVID-19-associated pulmonary aspergillosis (CAPA), obtained by the concomitant exposure to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein and A. fumigatus conidia, we found that the microbial compound indole-3-aldehyde (3-IAld) was able to ameliorate CAPA by working at multiple levels during viral infection and fungal superinfection, including epithelial barrier protection, promotion of antiviral responses, and limiting viral replication. As a consequence, 3-IAld limited the pathogenic sequelae of fungal superinfection as revealed by the controlled fungal burden and restrained inflammatory pathology. These results point to indole compounds as potential agents to prevent CAPA.
Insights
A novel compound, indole-3-aldehyde (3-IAld), effectively treats fungal infections like pulmonary aspergillosis following viral diseases such as COVID-19. This discovery offers potential new strategies for preventing severe fungal superinfections.
Area of Science:
- Mycology
- Virology
- Immunology
Background:
- Aspergillus fumigatus is a high-priority fungal pathogen.
- Severe viral infections, like COVID-19, can increase susceptibility to fungal infections.
- COVID-19-associated pulmonary aspergillosis (CAPA) is a serious complication.
Purpose of the Study:
- To investigate the therapeutic potential of indole-3-aldehyde (3-IAld) in a murine model of CAPA.
- To understand the mechanisms by which 3-IAld ameliorates CAPA.
Main Methods:
- A murine model was established by exposing mice to SARS-CoV-2 Spike protein and A. fumigatus conidia.
- The effects of 3-IAld on viral infection, fungal superinfection, and host responses were evaluated.
Main Results:
- 3-IAld protected the epithelial barrier and enhanced antiviral responses.
- 3-IAld limited viral replication and reduced fungal burden.
- 3-IAld mitigated the inflammatory pathology associated with fungal superinfection.
Conclusions:
- Indole compounds, specifically 3-IAld, show promise in preventing and treating CAPA.
- 3-IAld offers a multi-faceted approach to combatting fungal superinfections post-viral illness.
