Invasive Fungal Infections Complicating COVID-19: A Narrative Review

Giacomo Casalini,Spinello Antinori,Annalisa Ridolfo,Andrea Giacomelli,Cristina Gervasoni

doi:10.3390/jof7110921

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.

Highlights

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for a respiratory disease whose broad spectrum of severity ranges from asymptomatic or mildly symptomatic infection to severe bilateral pneumonia leading to progressive respiratory failure requiring non-invasive or invasive mechanical ventilation [1]
Invasive pulmonary aspergillosis (IPA) is a life-threatening disease caused by the ubiquitous Aspergillus mould, which is typically associated with immune system dysregulation due to chronic glucocorticoid therapy, prolonged neutropenia in hematological patients, stem cell/solid organ transplantation, or immunosuppressive treatment [6]
A number of cases of secondary bacterial and fungal infections have been reported since the emergence of COVID-19 and the publication of the first observational studies [90,130,197]; to the best of our knowledge, this is the only descriptive review of all of the types of IFI associated with COVID-19, the fungi involved, their clinical presentation and diagnostic difficulties, and their crude mortality rates

Summary

Introduction

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is responsible for a respiratory disease whose broad spectrum of severity ranges from asymptomatic or mildly symptomatic infection to severe bilateral pneumonia leading to progressive respiratory failure requiring non-invasive or invasive mechanical ventilation [1]. Many factors may be associated with these secondary infections, including immune system dysregulation and inhibition, epithelial barrier damage, the widespread use of antibiotics, admission to an intensive care unit (ICU), mechanical ventilation, and prolonged hospitalisation [1,2,4]. Invasive pulmonary aspergillosis (IPA) is a life-threatening disease caused by the ubiquitous Aspergillus mould, which is typically associated with immune system dysregulation due to chronic glucocorticoid therapy, prolonged neutropenia in hematological patients, stem cell/solid organ transplantation, or immunosuppressive treatment [6]. Since the first reports of COVID-19 in Wuhan, some authors have highlighted the risk of invasive fungal infections (IFIs) in critically ill COVID-19 patients on the basis of the increasing number of reports of IPA in ICU patients without immunological disorders, such as those with severe influenza or chronic obstructive pulmonary disease [7,8,9]. Various published case reports and observational studies of COVID-19-associated IPA (CAPA) have raised concerns about the burden of this infection and difficulties in diagnosing it (non-specific clinical and radiological findings, the uncertain diagnostic performance of microbiological assays in an ICU, difficulties in differentiating colonisation from infections, the fact that the current clinical diagnostic algorithm does not really apply to COVID-19 patients, and concerns about collecting lower respiratory tract samples because of the risk of contagion) [10,11]

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