Coronavirus Disease 2019–Associated Mucormycosis: Risk Factors and Mechanisms of Disease

Narayanan, Shivakumar; Chua, Joel V; Baddley, John W.

doi:10.1093/cid/ciab726

Cited by 60 publications

(76 citation statements)

References 33 publications

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“…Our search identified a total of 3185 cases distributed in 33 case reports/series and 12 observational studies, with an average incidence of 8.7%; many of these came from India (12/33 case reports, 36%, and 7/12 observational studies, 58.3%). Rhino-orbital mucormycosis was the most frequently reported (48.6% overall), and the strong association between COVID-19 and mucormycosis in the Indian population is probably due to a convergence of multiple concomitant risk factors: a higher baseline prevalence of the disease, favourable environmental factors (humidity, soil contamination, air pollution), a high and increasing prevalence of uncontrolled diabetes mellitus, and the widespread use of corticosteroids to treat COVID-19 (often beyond the indications of the guidelines) and possibly other immunosuppressive agents (i.e., anti-IL-6 agents) [176,212]. More than 76% of the candidemia patients considered in this review were affected by diabetes mellitus with poor glycaemic control, and almost 73% received systemic corticosteroids, which may worsen glycaemic control and presumably reduce host immune defences.…”

Section: Discussionmentioning

confidence: 99%

Invasive Fungal Infections Complicating COVID-19: A Narrative Review

Casalini

Giacomelli

Ridolfo

et al. 2021

JoF

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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.

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Section: Discussionmentioning

confidence: 99%

Invasive Fungal Infections Complicating COVID-19: A Narrative Review

Casalini

Giacomelli

Ridolfo

et al. 2021

JoF

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“…Corticosteroids tend to cause lymphopenia and T lymphocyte dysregulation. They may also induce hyperglycaemia in patients with diabetes [ 62 , 63 ]. In a COVID Care Centre in Western India, 3.36% (32 of 953) patients experienced CAM, while 93% of them had prior corticosteroids exposure [ 64 ].…”

Section: Identifying Risk Factors and Implementing Preventive Measuresmentioning

confidence: 99%

COVID-19–associated mucormycosis: Evidence-based critical review of an emerging infection burden during the pandemic’s second wave in India

et al. 2021

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Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19–induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19–associated mucormycosis in India.

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“…Importantly, mucormycosis associated with influenza has also been described ( 110 ). Major risk factors include patients receiving systemic corticosteroid treatment or suffering from uncontrolled diabetes ( 111 , 112 ). Hyperglycemia increases the expression of the glucose-regulated protein (GRP78), which acts as a receptor for the CotH protein kinase present in Rhizopus spores, helping the fungus to adhere and invade endothelial and nasal epithelial cells ( 113 – 115 ).…”

Section: Fungal Coinfections In Respiratory Viral Diseasementioning

confidence: 99%