Microbial and clinical epidemiology of invasive fungal rhinosinusitis in hospitalized COVID-19 patients, the divergent causative agents.

Since COVID-19 spread worldwide, invasive fungal rhinosinusitis (IFRS) has emerged in immunocompromised patients as a new clinical challenge. In this study, clinical specimens of 89 COVID-19 patients who presented clinical and radiological evidence suggestive of IFRS were examined by direct microscopy, histopathology, and culture, and the isolated colonies were identified through DNA sequence analysis. Fungal elements were microscopically observed in 84.27% of the patients. Males (53.9%) and patients over 40 (95.5%) were more commonly affected than others. Headache (94.4%) and retro-orbital pain (87.6%) were the most common symptoms, followed by ptosis/proptosis/eyelid swelling (52.8%), and 74 patients underwent surgery and debridement. The most common predisposing factors were steroid therapy (n = 83, 93.3%), diabetes mellitus (n = 63, 70.8%), and hypertension (n = 42, 47.2%). The culture was positive for 60.67% of the confirmed cases, and Mucorales were the most prevalent (48.14%) causative fungal agents. Different species of Aspergillus (29.63%) and Fusarium (3.7%) and a mix of two filamentous fungi (16.67%) were other causative agents. For 21 patients, no growth was seen in culture despite a positive result on microscopic examinations. In PCR-sequencing of 53 isolates, divergent fungal taxons, including 8 genera and 17 species, were identified as followed: Rhizopus oryzae (n = 22), Aspergillus flavus (n = 10), A. fumigatus (n = 4), A. niger (n = 3), R. microsporus (n = 2), Mucor circinelloides, Lichtheimia ramosa, Apophysomyces variabilis, A. tubingensis, A. alliaceus, A. nidulans, A. calidoustus, Fusarium fujikuroi/proliferatum, F. oxysporum, F. solani, Lomentospora prolificans, and Candida albicans (each n = 1). In conclusion, a diverse set of species involved in COVID-19-associated IFRS was observed in this study. Our data encourage specialist physicians to consider the possibility of involving various species in IFRS in immunocompromised and COVID-19 patients. In light of utilizing molecular identification approaches, the current knowledge of microbial epidemiology of invasive fungal infections, especially IFRS, may change dramatically.

Invasive fungal rhinosinusitis (IFRS) may infect people with diabetes, cancer, or COVID-19. In this study, various types of fungi were identified from COVID-19-associated-IFRS, encouraging physicians to consider specific treatments.

Interaction of eNOS polymorphism with MTHFR variants increase the risk of diabetic nephropathy and its progression in type 2 diabetes mellitus patients.

The present study has investigated the role of endothelial nitric oxide (eNOS) G894T polymorphism and its interaction with methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C variants on the predisposition to diabetic nephropathy and its progression. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method the eNOS G894T and MTHFR polymorphisms were detected in 72 microalbuminuric, 68 macroalbuminuric, and 72 normoalbuinuric type 2 diabetes mellitus (T2DM) patients from Western Iran. The presence of GT and GT + TT genotypes of eNOS were associated with insignificantly 1.86- and 1.68-fold increased risk of macroalbuminuria, respectively and 1.21- and 1.13-fold increased risk of microalbuminuria, respectively. However, the concomitant presence of eNOST and MTHFR 1298C alleles were significantly increased the risk of macroalbuminuria (6.6-fold, P < 0.001) and progression from micro- to macro-albuminuria (3.85 times, P = 0.011). Also, the presence of both alleles of eNOST and MTHFR 677T were significantly associated with increased risk of macroalbuminuria (4.8-fold, P = 0.005). The presence of GT + TT genotypes of eNOS was significantly associated with increased risk of coronary artery disease in micro- and macro-albuminuric patients compared to normoalbuminuric patients. The concomitant presence of three mutant alleles significantly increased the risk of macroalbuminuria and progression from micro- to macro-albuminuria 38.5- and 10.5-fold, respectively. Our study indicated that eNOS T allele interacts with MTHFR variants, especially MTHFR A1298C to increase the risk of macroalbuminuria and progression from micro-to macro-albuminuria. Also, Interaction between three alleles of eNOST, MTHFR 677T, and 1298C highly increased the risk of macroalbuminuria and progression of diabetic nephropathy in T2DM patients.