Increased Fungal Infection Mortality Induced by Concurrent Viral Cellular Manipulations

Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal infections. These viral manipulations include the following: (1) inhibiting transcription factors and cytokine expressions, (2) impairing defensive protein expressions, (3) inhibiting defenses by manipulating cellular sensors and signaling pathways, (4) inhibiting defenses by secreting exosomes, and (5) stimulating glucocorticoid synthesis to suppress immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. The highest mortality respiratory viral pandemics up to now have had substantially boosted mortalities by inducing secondary bacterial pneumonias. However, numerous animal species besides humans are also carriers of endemic infections by viral and multidrug-resistant fungal pathogens. The vast multi-species scope of endemic infection opportunities make it plausible that the pro-fungal manipulations of a respiratory virus can someday evolve to enable a very high mortality rate viral pandemic inducing multidrug-resistant secondary fungal pathogen infections. Since such pandemics can quickly spread world-wide and outrun existing treatments, it would be worthwhile to develop new antifungal treatments well before such a high mortality event occurs.