Lethal synergistic infections by two concurrent respiratory pathogens

Lethal synergistic infections by concurrent pathogens have occurred in humans, including human immunodeficiency virus and Mycobacterium tuberculosis infections, or in animal or human models of influenza virus, or bacteria, e.g., Streptococcus pneumoniae, concurrent with severe acute respiratory syndrome coronavirus 2 (SARS–CoV–2). However, the intracellular synergistic interaction possibilities between two respiratory viral pathogens, or between viral and fungal pathogens, merits additional examination. The requirements for synergistic concurrent pathogen infections are: a) relatively little detrimental interference between two pathogens, b) one pathogen having the capability of directly or indirectly assisting the second pathogen by direct immuno–manipulation or indirect provision of infection opportunities and/or metabolic assistance, c) substantial human or environmental prevalence, possibly including a prevalence in any type of health–care facilities or other locations having congregations of potentially infected human or animal vectors and d) substantial transmissibility of the pathogens, which would make their concurrent pathogen infections much more probable. A new definition of pathogen synergy is proposed: “pathogen synergy is an interaction of two or more pathogens during concurrent infections causing an increased infection severity compared to mono–infections by the individual pathogens.” Non–respiratory pathogens can also concurrently infect organs besides the lungs. However, the air–transmissible respiratory pathogens, particularly the RNA viruses, can enable highly widespread and synergistic concurrent infections. For instance, certain strains of coronaviruses, influenza viruses and similar respiratory viruses, are highly transmissible and/or widely prevalent in various vectors for transmission to humans and have numerous capabilities for altering lung immune defenses.