Rhino-orbito-cerebral mucormycosis caused by Rhizopus microsporus var. microsporus in a diabetic patient with COVID-19

Abstract COVID-19 disease caused by the SARS-CoV-2 coronavirus causes a wide range of clinical manifestations, ranging from mild to severe, with the main ones affecting the respiratory tract, such as pneumonia. In patients with greater severity, the high frequency of bacterial and fungal coinfection stands out, a situation related both to the patient's pre-existing comorbidities and due to the hospitalization itself. Cases of mucormycosis associated with COVID-19 were highlighted in the lay and scientific media, with the increase in mycosis cases being directly and indirectly attributed to the viral infection. This report describes a case of rhino-orbito-cerebral mucormycosis in a diabetic patient hospitalized for COVID-19, whose diagnosis was confirmed by identifying the agent Rhizopus microsporus var. microsporus through culture for fungi and PCR examination.

Rhino-orbito-cerebral mucormycosis caused by Rhizopus microsporus var. microsporus in a diabetic patient with COVID-19.

COVID-19 disease caused by the SARS-CoV-2 coronavirus causes a wide range of clinical manifestations, ranging from mild to severe, with the main ones affecting the respiratory tract, such as pneumonia. In patients with greater severity, the high frequency of bacterial and fungal coinfection stands out, a situation related both to the patient's pre-existing comorbidities and due to the hospitalization itself. Cases of mucormycosis associated with COVID-19 were highlighted in the lay and scientific media, with the increase in mycosis cases being directly and indirectly attributed to the viral infection. This report describes a case of rhino-orbito-cerebral mucormycosis in a diabetic patient hospitalized for COVID-19, whose diagnosis was confirmed by identifying the agent Rhizopus microsporus var. microsporus through culture for fungi and PCR examination.

The Dermatophyte Trichophyton rubrum Induces Neutrophil Extracellular Traps Release by Human Neutrophils.

Neutrophils are the first leukocytes recruited to the site of infection and are thought to be responsible for fungal elimination from the skin such as dermatophytes. Neutrophils are able to secrete reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) that can kill different fungi, including Aspergillus, spp., Candida albicans, and Phialophora verrucosa. However, NET production in response to Trichophyton rubrum, the main etiologic agent of dermatophytosis, has yet to be studied. We demonstrated that human neutrophils produce NETs against different morphotypes of T. rubrum in a dose-dependent manner and NET formation is dependent on ROS production. In addition, ROS production by human neutrophils in response to T. rubrum is dependent on NADPH oxidase, but not on fungal viability. NETs mediated killing of T. rubrum. Collectively, these results demonstrate that T. rubrum was able to trigger the production of NETs, suggesting that these extracellular structures may represent an important innate immune effector mechanism controlling physiological response to T. rubrum infection.

Trichophyton rubrum Elicits Phagocytic and Pro-inflammatory Responses in Human Monocytes Through Toll-Like Receptor 2.

Dermatophytosis is a superficial fungal infection mostly restricted to keratinized tissues such as skin, hair, and nails but with potential to cause invasive or even systemic disease in immunocompromised patients. Trichophyton rubrum is the main etiologic agent, accounting for approximately 80% of the cases. Mononuclear phagocytes respond to pathogens through phagocytosis followed by production of several antimicrobial molecules, such as reactive oxygen and nitrogen species, and failure in doing so may contribute to development of chronic fungal infections. Toll-like receptors (TLRs) located on the surface of phagocytic cells bind either directly to target particles or through opsonizing ligands and trigger an actin-mediated ingestion. Even though the mechanisms involved in TLR-mediated cytokine responses are well established, the contribution of TLR in the recognition of T. rubrum by adherent monocytes remains unclear. Here, we report that phagocytosis of T. rubrum conidia by adherent monocytes is mediated by TLR2. Blockade of TLR2 by neutralizing antibodies impaired the fungicidal activity of monocytes as well their secretion of tumor necrosis factor (TNF)-α, but neither nitric oxide (NO) production nor interleukin (IL)-10 secretion was disturbed. So far, our data suggest that TLR2 is required for efficient conidial phagocytosis, and the absence of TLR2 signaling in human monocytes may impair the subsequent inflammatory response. These findings expand our understanding of phagocyte modulation by this important fungal pathogen and may represent a potential target for interventions aiming at enhancing antifungal immune responses.

In situ immune response in human dermatophytosis: possible role of Langerhans cells (CD1a+) as a risk factor for dermatophyte infection.

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.