Silva Danielle L, Peres Nalu T A, Santos Daniel A
Microbiology Department, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, State of Minas Gerais, Brazil.
Brazilian National Institute of Science and Technology in Human Pathogenic Fungi (INCT-FUNVIR), São Paulo, Brazil.
mBio. 2025 May 14;16(5):e0056225. doi: 10.1128/mbio.00562-25. Epub 2025 Apr 2.
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, , and 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 and 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.
混合感染被定义为在同一宿主内至少出现两种基因不同的感染因子。从历史上看，真菌感染一直被忽视，导致对其对公共卫生系统影响的低估。然而，真菌混合感染已变得越来越普遍，成为一个重大的全球健康问题。本综述探讨了通常与人类免疫缺陷病毒（HIV）、严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、流感以及结核分枝杆菌和曲霉菌种相关的真菌混合感染。这些感染包括念珠菌病、曲霉病、副球孢子菌病、隐球菌病、组织胞浆菌病、肺孢子菌病、孢子丝菌病和毛霉病。我们讨论了促成这些混合感染发生的关键局部和全身机制。HIV感染CD4+细胞，导致全身免疫抑制，尤其损害适应性免疫反应。对SARS-CoV-2感染的炎症反应破坏了肺部和全身的稳态，使个体更容易发生局部和播散性真菌混合感染。严重流感通过触发促炎细胞因子的产生促进真菌混合感染，这些细胞因子会破坏上皮-内皮屏障并损害真菌细胞的识别和吞噬作用。结核病可使正常肺实质被胶原组织取代，导致肺结构改变，损害其功能。混合感染期间结核分枝杆菌和曲霉菌之间的相互作用涉及对铁可用性的竞争以及对铁缺乏的适应性反应。因此，本综述详细阐述了每种基础疾病与真菌混合感染之间的具体相互作用。此外，我们强调了与混合感染相关的危险因素、病理生理学、流行病学以及早期诊断的挑战。认识到真菌混合感染给全球带来的巨大公共卫生负担对于提高生存率至关重要。
