Abstract

The treatment of fungal infections presents significant challenges due to the lack of standardized diagnostic procedures, a restricted range of antifungal treatments, and the risk of harmful interactions between antifungal medications and the immunosuppressive drugs used in anti-inflammatory treatment for critically ill patients with COVID-19. Mucormycosis and aspergillosis are the primary invasive fungal infections in patients with severe COVID-19, occurring singly or in combination. Histopathological examination is a vital diagnostic technique that details the presence and invasion of fungi within tissues and blood vessels, and the body’s response to the infection. However, the pathology report omits information on the most common fungi associated with the observed morphology, as well as other potential fungi and parasites that ought to be included in the differential diagnosis. This research marks significance in diagnosing fungal infections, such as mucormycosis and aspergillosis associated to COVID-19 by field emission scanning electron microscopy (FESEM) imaging to examine unstained histopathology slides, allowing for a detailed morphological analysis of the fungus. FESEM provides an unprecedented resolution and detail, surpassing traditional Hematoxylin & Eosin (H&E) and Grocott’s Methenamine Silver (GMS) staining methods in identifying and differentiating dual fungal infections and diverse fungal species. The findings underscore the critical need for individualized treatment plans for patients severely affected by COVID-19 and compounded by secondary fungal infections. The high-magnification micrographs reveal specific fungal morphology and reproductive patterns. Current treatment protocols largely depend on broad-spectrum antifungal therapies. However this FESEM guided diagnostic approach can help in targeted patient specific anti fungal therapies. Such precision could lead to more effective early interventions, addressing the complex management required for severe COVID-19 cases with coexisting fungal infections. This approach significantly advances disease management and patient recovery, advocating for personalized, precision medicine in tackling this multifaceted clinical challenge.

Graphical Abstract

中文翻译：

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使用 FESEM 成像精确检测真菌合并感染，以增强 COVID-19 治疗策略

摘要

由于缺乏标准化的诊断程序、抗真菌治疗的范围有限，以及抗真菌药物与新冠危重患者抗炎治疗中使用的免疫抑制药物之间存在有害相互作用的风险，真菌感染的治疗面临着巨大的挑战。 19.毛霉菌病和曲霉菌病是重症 COVID-19 患者的主要侵袭性真菌感染，可单独或联合发生。组织病理学检查是一项重要的诊断技术，可详细了解组织和血管内真菌的存在和入侵，以及身体对感染的反应。然而，病理报告忽略了与观察到的形态相关的最常见真菌的信息，以及应纳入鉴别诊断的其他潜在真菌和寄生虫的信息。这项研究对于通过场发射扫描电子显微镜 (FESEM) 成像检查未染色的组织病理学切片来诊断真菌感染（例如与 COVID-19 相关的毛霉菌病和曲霉病）具有重要意义，从而可以对真菌进行详细的形态学分析。 FESEM 提供了前所未有的分辨率和细节，在识别和区分双重真菌感染和不同真菌种类方面超越了传统的苏木精和曙红 (H&E) 和 Grocott 的乌洛托品银 (GMS) 染色方法。研究结果强调，对于受 COVID-19 严重影响并伴有继发真菌感染的患者，迫切需要制定个性化治疗计划。高倍显微照片揭示了特定的真菌形态和繁殖模式。目前的治疗方案很大程度上依赖于广谱抗真菌疗法。然而，这种 FESEM 引导的诊断方法可以帮助有针对性的患者特异性抗真菌治疗。这种精确度可以带来更有效的早期干预措施，解决同时存在真菌感染的严重 COVID-19 病例所需的复杂管理。这种方法显着促进了疾病管理和患者康复，倡导个性化、精准医疗来应对这一多方面的临床挑战。

图形概要