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Invasive Fungal Infections Complicating COVID-19: A Narrative Review
Giacomo Casalini1, Andrea Giacomelli1,2, Annalisa Ridolfo2
1Luigi Sacco Department of Biomedical and Clinical Sciences, Università degli Studi di Milano, 20157 Milan, Italy.
Abstract:
Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium.
Insights
Invasive fungal infections (IFIs) significantly increase mortality in COVID-19 patients, particularly in ICUs. This review highlights challenges in diagnosing and treating IFIs like aspergillosis, candidemia, and mucormycosis in COVID-19 survivors.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Pulmonology
Background:
- Invasive fungal infections (IFIs) are serious complications in COVID-19 patients, leading to increased mortality, especially in intensive care unit (ICU) settings.
- COVID-19 patients often present with risk factors for secondary IFIs, including prolonged hospitalization, mechanical ventilation, broad-spectrum antibiotics, and indwelling catheters.
- SARS-CoV-2 infection may impair host immune responses, increasing susceptibility to a range of opportunistic fungal pathogens.
Purpose of the Study:
- To review the incidence, diagnostic challenges, and outcomes of various invasive fungal infections complicating COVID-19.
- To analyze data from 168 studies involving 58,784 COVID-19 patients with 4,099 cases of IFIs.
- To discuss specific IFIs including COVID-19-associated invasive pulmonary aspergillosis (CAPA), candidemia, and mucormycosis.
Main Methods:
- Narrative review of 168 studies including observational studies and case reports.
- Analysis of 4,099 cases of IFIs across 58,784 COVID-19 patients.
- Focus on diagnostic methods (culture, biomarkers, histopathology) and reported mortality rates for different IFIs.
Main Results:
- COVID-19-associated invasive pulmonary aspergillosis (CAPA) presents diagnostic challenges due to non-specific symptoms and limitations of current diagnostic algorithms.
- Candidemia shows high crude mortality rates (56.1% in case reports, 74.8% in observational studies) in critically ill COVID-19 patients.
- Mucormycosis, particularly rhino-orbital, is strongly associated with uncontrolled diabetes; high mortality rates are reported (50.8% in case reports, 16% in observational studies).
- Other IFIs like Pneumocystis pneumonia, cryptococcosis, and histoplasmosis were also observed, indicating a potential immune-dampening effect of SARS-CoV-2.
Conclusions:
- IFIs are significant contributors to morbidity and mortality in COVID-19 patients.
- Accurate and timely diagnosis of IFIs in COVID-19 requires a multi-faceted approach, often combining clinical, microbiological, and sometimes histopathological data.
- High mortality rates associated with IFIs underscore the need for increased awareness and effective management strategies in this patient population.
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