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呼吸道病毒感染常诱发继发性侵袭性真菌感染，显著增加了重症患者的病死率，已成为全球公共卫生面临的严峻挑战。本文系统综述了呼吸道病毒继发真菌感染的流行病学特征、协同致病机制、诊疗困境及应对策略。在致病机制方面，病毒感染通过破坏气道上皮物理屏障并重塑缺氧微环境，为真菌入侵创造条件；更关键的是，病毒通过干扰素（Interferon, IFN）动力学失调、抑制中性粒细胞募集与杀菌功能等途径诱导“先天免疫麻痹”，并导致Th17/Treg免疫轴失衡及交叉反应调节障碍，严重削弱了宿主对曲霉、毛霉等真菌的防御能力。临床上，流感相关性肺曲霉病和重症病毒性肺炎相关肺曲霉病已确立为独立的高危临床表型，且呈现出向既往健康人群扩散的趋势。目前，呼吸道病毒继发真菌共感染面临临床症状重叠导致早期诊断困难、真菌耐药性增强及抗病毒-抗真菌药物相互拮抗的诊疗困境。对此，本文提出未来应聚焦于强化早期干预，开发基于微流控与人工智能的精准诊断技术；针对耐药机制探索新药物靶点；实施基于免疫状态评估的个体化免疫调节策略；并挖掘中西医结合治疗在调节“肠-肺轴”微生态中的潜力，旨在为改善此类重症共感染患者的预后提供理论依据与临床参考。
Abstract：Respiratory viral infections frequently predispose patients to secondary invasive fungal infections, significantly increasing mortality among critically ill individuals and posing a serious global public health challenge. This article systematically summarizes the epidemiological characteristics, synergistic pathogenic mechanisms, and major diagnostic and therapeutic challenges associated with secondary fungal infections following respiratory viral illnesses, as well as potential response strategies. Mechanistically, respiratory viruses facilitate fungal invasion by disrupting the physical integrity of the airway epithelial barrier and remodeling the hypoxic microenvironment. More importantly, viral infections induce a state of “innate immune paralysis” through dysregulated interferon(IFN) kinetics and impaired neutrophil recruitment and fungicidal activity, accompanied by imbalance of the Th17/Treg immune axis and defects in cross-reactive immune regulation, which together severely compromise host defense against fungi such as Aspergillus and Mucor species. Clinically, influenza-associated pulmonary aspergillosis and pulmonary aspergillosis associated with severe viral pneumonia have been established as distinct high-risk clinical phenotypes, with an emerging trend toward involvement of previously immunocompetent populations. At present, secondary fungal co-infections complicating respiratory viral diseases face substantial diagnostic and therapeutic challenges, including overlapping clinical manifestations that hinder early diagnosis, increasing antifungal resistance, and antagonistic interactions between antiviral and antifungal therapies. In this context, future efforts should prioritize strengthening early warning systems; developing precise diagnostic technologies based on microfluidics and artificial intelligence; identifying novel therapeutic targets to overcome antifungal resistance; implementing individualized immunomodulatory strategies guided by immune status assessment; and exploring the potential of integrative Chinese and Western medical approaches in modulating the gut-lung axis microecology. Collectively, these strategies aim to provide a theoretical framework and clinical reference for improving outcomes in patients with severe viral–fungal co-infections.
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250399
中图分类号:R56;R519
引用信息:
[1]穆舒怡,吕安淇,费凯,等.呼吸道病毒继发真菌感染的协同致病机制及诊疗困境[J].病毒学报,2026,42(02):673-682.DOI:10.13242/j.cnki.bingduxuebao.250399.
基金信息:
国家自然科学基金面上项目（项目号：82174286）,题目：基于H1N1感染气道上皮协同固有免疫活化研究中药羌竹清感方肺损伤保护的效应机制;国家自然科学基金青年科学基金项目（项目号：82205005）,题目：羌竹清感方及拆方对病毒性肺炎上皮/内皮损伤与MΦ介导免疫活化放大互作关键环节的效应机制研究; 上海市浦东新区卫生健康委员会项目（项目号：2026-PWYC-19）,题目：重症肺炎肺损伤中西医干预临床研究~~
2025-12-15
2025
2025-12-27
2026-02-23
2026
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2026-02-24
2026-02-24
2026-02-24