Key fungal coinfections: epidemiology, mechanisms of pathogenesis, and beyond

Abstract

Coinfection is defined as the occurrence of at least two genetically distinct infectious agents within the same host. Historically, fungal infections have been neglected, leading to an underestimation of their impact on public health systems. However, fungal coinfections have become increasingly prevalent, emerging as a significant global health concern. This review explores fungal coinfections commonly associated with HIV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, Mycobacterium tuberculosis, and Pseudomonas species. These include candidiasis, aspergillosis, paracoccidioidomycosis, cryptococcosis, histoplasmosis, pneumocystosis, sporotrichosis, and mucormycosis. We discuss the key local and systemic mechanisms that contribute to the occurrence of these coinfections. HIV infects CD4+ cells, causing systemic immunosuppression, particularly impairing the adaptive immune response. The inflammatory response to SARS-CoV-2 infection disrupts both pulmonary and systemic homeostasis, rendering individuals more vulnerable to local and disseminated fungal coinfections. Severe influenza promotes fungal coinfections by triggering the production of pro-inflammatory cytokines, which damage the epithelial-endothelial barrier and impair the recognition and phagocytosis of fungal cells. Tuberculosis can replace normal lung parenchyma with collagen tissue, leading to alterations in lung architecture, compromising its function. Interaction between Pseudomonas and Aspergillus during coinfection involves the competition for iron availability and an adaptive response to its deprivation. Therefore, the specific interactions between each underlying disease and fungal coinfections are detailed in this review. In addition, we highlight the risk factors associated with coinfections, pathophysiology, epidemiology, and the challenges of early diagnosis. Recognizing the substantial worldwide public health burden posed by fungal coinfections is crucial to improve survival rates.

Keywords: coinfection; fungal disease; infectious disease; neglected disease; pathogens.

Fig 1

Predisposing diseases for fungal coinfections. Each underlying disease is represented by a specific color, which is also applied to the associated fungal coinfection. The intersections indicate predispositions to the respective fungal coinfection in the context of the underlying disease. In the case of aspergillosis, the asterisk (*) and specific color represent its coinfection with Pseudomonas and influenza. PCM: paracoccidioidomycosis. COVID-19: coronavirus disease 2019. HIV: human immunodeficiency virus.