Patients with severe COVID-19, such as individuals in intensive care units (ICU), are exceptionally susceptible to bacterial and fungal infections. The most prevalent fungal infections are aspergillosis and candidemia. Nonetheless, other fungal species (for instance, Histoplasma spp., Rhizopus spp., Mucor spp., Cryptococcus spp.) have recently been increasingly linked to opportunistic fungal diseases in COVID-19 patients. These fungal co-infections are described with rising incidence, severe illness, and death that is associated with host immune response. Awareness of the high risks of the occurrence of fungal co-infections is crucial to downgrade any arrear in diagnosis and treatment to support the prevention of severe illness and death directly related to these infections. This review analyses the fungal infections, treatments, outcome, and immune response, considering the possible role of the microbiome in these patients. The search was performed in Medline (PubMed), using the words “fungal infections COVID-19”, between 2020–2021.

The evolution of drug resistance of Candida species to conventional antifungal agents has been a major medical challenge worldwide; attempt to use the potential antifungal agents with appropriate therapy efficacy and minimum effects is considerably growing. This study was conducted to evaluate the use of nanogel as a nanocarrier for pharmaceutical application of farnesol. The nanogels were synthetized using alginate (AL) and chitosan (CS) polymers containing 300 mM of farnesol in the nanorange 42-70 nm size. In vitro release studies indicated that release of farnesol from CS and AL nanogels was as 58% and 37%, respectively. Chitosan nanogel showed more in inhibitory zone as compared to AL nanogel (9 mm). Also, cytotoxicity assay showed no significant difference between control and treatment groups (p>.05). Finally, the effect of nanogels on genes expression of HWP1, SAP6 and Rim101 in Candida albicans ATCC10231 was assessed using real-time polymerase chain reaction (PCR). Expression of HWP1 and SAP6 genes in C. albicans treated with CS nanogel was significantly decreased (p<.01). In general, the obtained finding showed that, CS nanogel contains farnesol with proper antifungal activity and as a new approach used in pharmaceutical applications against C. albicans; however, more studies in vitro and in vivo are needed in the future.

Background:Some genes may be associated with Candida albicans resistance to azoles. Pir1 gene is described as responsible to induce resistance in C. albicans.Objectives:The current study aimed to find the relationship between fluconazole resistance and Pir1 protein (Pir1p) overexpression in the females with recurrent C. albicans vaginitis requiring longer fluconazole therapy.Patients and Methods:A total of 52l vaginal samples were obtained from the females with C. albicans vaginitis. The azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute (CLSI) protocol for disk diffusion method and inhibition zone for fluconazole. Expression of pir1 gene and fluconazole -resistance were evaluated using polymerase chain reaction (PCR) in C. albicans.Results:In the 52 isolates, 49 (94%) were resistant to fluconazole. Overexpression of Pir1 gene was detected in 47 (96%) fluconazole-resistant C. albicans isolates.Conclusions:The findings show fluconazole -resistance in C. albicans isolates with overexpression of Pir1p.

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Background and Objectives: Vulvovaginal candidiasis (VVC) is a mucous membrane infection, with an increased rate of antifungal resistance of Candida species. In this study, the in vitro efficacy of farnesol alone or in combination with traditional antifungals was assessed against resistant Candida strains recovered from women with VVC. Materials and Methods: Eighty Candida isolates were identified by multiplex polymerase chain reaction (PCR), and the antifungal susceptibility to amphotericin B (AMB), fluconazole (FLU), itraconazole (ITZ), voriconazole (VOR), clotrimazole (CTZ), and farnesol was tested by the standard microdilution method. The combinations of farnesol with each antifungal were calculated based on the fractional inhibitory concentration index (FICI). Result: Candida glabrata was the predominant species (48.75%) isolated from vaginal discharges, followed by C. albicans (43.75%), C. parapsilosis (3.75%), a mixed infection of C. albicans and C. glabrata (2.5%) and C. albicans and C. parapsilosis (1%). C. albicans and C. glabrata isolates had lower susceptibility to FLU (31.4% and 23.0%, respectively) and CTZ (37.1% and 33.3%, respectively). Importantly, there was “synergism” between farnesol–FLU and farnesol–ITZ against C. albicans and C. parapsilosis (FICI = 0.5 and 0.35, respectively), reverting the original azole-resistant profile. Conclusion: These findings indicate that farnesol can revert the resistance profile of azole by enhancing the activity of FLU and ITZ in resistant Candida isolates, which is a clinically promising result.