Coronavirus disease 2019 (COVID-19) can lead to serious illness and death, and thus, it is particularly important to predict the severity and prognosis of COVID-19. The Sequential Organ Failure Assessment (SOFA) score has been used to predict the clinical outcomes of patients with multiple organ failure requiring intensive care. Therefore, we retrospectively analyzed the clinical characteristics, risk factors, and relationship between the SOFA score and the prognosis of COVID-19 patients. We retrospectively included all patients ≥18 years old who were diagnosed with COVID-19 in the laboratory continuously admitted to Jingzhou Central Hospital from January 16, 2020 to March 23, 2020. The demographic, clinical manifestations, complications, laboratory results, and clinical outcomes of patients infected with the severe acute respiratory syndrome coronavirus-2 were collected and analyzed. Clinical variables were compared between patients with mild and severe COVID-19. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for severe COVID-19. The Cox proportional hazards model was used to analyze risk factors for hospital-related death. Survival analysis was performed by the Kaplan–Meier method, and survival differences were assessed by the log-rank test. Receiver operating characteristic (ROC) curves of the SOFA score in different situations were drawn, and the area under the ROC curve was calculated. A total of 117 patients with confirmed diagnoses of COVID-19 were retrospectively analyzed, of which 108 patients were discharged and 9 patients died. The median age of the patients was 50.0 years old (interquartile range [IQR], 35.5–62.0). 63 patients had comorbidities, of which hypertension (27.4%) was the most frequent comorbidities, followed by diabetes (8.5%), stroke (4.3%), coronary heart disease (3.4%), and chronic liver disease (3.4%). The most common symptoms upon admission were fever (82.9%) and dry cough (70.1%). Regression analysis showed that high SOFA scores, advanced age, and hypertension were associated with severe COVID-19. The median SOFA score of all patients was 2 (IQR, 1–3). Patients with severe COVID-19 exhibited a significantly higher SOFA score than patients with mild COVID-19 (3 [IQR, 2–4] vs 1 [IQR, 0–1]; P < .001). The SOFA score can better identify severe COVID-19, with an odds ratio of 5.851 (95% CI: 3.044–11.245; P < .001). The area under the ROC curve (AUC) was used to evaluate the diagnostic accuracy of the SOFA score in predicting severe COVID-19 (cutoff value = 2; AUC = 0.908 [95% CI: 0.857–0.960]; sensitivity: 85.20%; specificity: 80.40%) and the risk of death in COVID-19 patients (cutoff value = 5; AUC = 0.995 [95% CI: 0.985–1.000]; sensitivity: 100.00%; specificity: 95.40%). Regarding the 60-day mortality rates of patients in the 2 groups classified by the optimal cutoff value of the SOFA score (5), patients in the high SOFA score group (SOFA score ≥5) had a significantly greater risk of death than those in the low SOFA score group (SOFA score < 5). The SOFA score could be used to evaluate the severity and 60-day mortality of COVID-19. The SOFA score may be an independent risk factor for in-hospital death.

Limited options of antifungals and the emergence of drug resistance in fungal pathogens has been a multifaceted clinical challenge. Combination therapy represents a valuable alternative to antifungal monotherapy.

Background: Metabolic associated fatty liver disease (MAFLD) has become the most common liver disease globally, yet no new drugs have been approved for clinical treatment. Therefore, we investigated the relationship between dietary intake of soy-derived daidzein and MAFLD, to find potentially effective treatments.Methods: We conducted a cross-sectional study using data from 1,476 participants in National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018 and their associated daidzein intake from the flavonoid database in the USDA Food and Nutrient Database for Dietary Studies (FNDDS). We investigated the relationship between MAFLD status, controlled attenuation parameter (CAP), AST/Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), liver stiffness measurement (LSM), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), hepatic steatosis index (HSI), fatty liver index (FLI), and daidzein intake by adjusting for confounding variables using binary logistic regression models and linear regression models.Results: In the multivariable-adjusted model II, there was a negative association between daidzein intake and the incidence of MAFLD (OR for Q4 versus Q1 was 0.65, 95% confidence interval [CI] = 0.46–0.91, p = 0.0114, p for trend was 0.0190). CAP was also negatively associated with daidzein intake, β = −0.37, 95% CI: −0.63 to −0.12, p = 0.0046 in model II after adjusting for age, sex, race, marital status, education level, family income-to-poverty ratio (PIR), smoking, and alcohol consumption. Stratified by quartiles of daidzein intake, trend analysis of the relationship between daidzein intake and CAP remained significant (p for trend = 0.0054). In addition, we also found that HSI, FLI, and NFS were negatively correlated with daidzein intake. LSM was negatively related to daidzein intake but had no statistical significance. The correlation between APRI, FIB-4, and daidzein intake was not strong (although p < 0.05, β values were all 0).Conclusion: We found that MAFLD prevalence, CAP, HSI, and FLI, all decreased with increased daidzein intake, suggesting that daidzein intake may improve hepatic steatosis. Therefore, dietary patterns of soy food or supplement consumption may be a valuable strategy to reduce the disease burden and the prevalence of MAFLD.

Candida species are the most common fungal pathogens to infect humans, and can cause life-threatening illnesses in individuals with compromised immune systems. Fluconazole (FLU) is the most frequently administered antifungal drug, but its therapeutic efficacy has been limited by the emergence of drug-resistant strains. When co-administered with minocycline (MIN), FLU can synergistically treat clinical Candida albicans isolates in vitro and in vivo. However, there have been few reports regarding the synergistic efficacy of MIN and azoles when used to treat FLU-resistant Candida species, including Candida auris. Herein, we conducted a microdilution assay wherein we found that MIN and posaconazole (POS) showed the best in vitro synergy effect, functioning against 94% (29/31) of tested strains, whereas combinations of MIN+itraconazole (ITC), MIN+voriconazole (VOR), and MIN+VOR exhibited synergistic activity against 84 (26/31), 65 (20/31), and 45% (14/31) of tested strains, respectively. No antagonistic activity was observed for any of these combinations. In vivo experiments were conducted in Galleria mellonella, revealing that combination treatment with MIN and azoles improved survival rates of larvae infected with FLU-resistant Candida. Together, these results highlight MIN as a promising synergistic compound that can be used to improve the efficacy of azoles in the treatment of FLU-resistant Candida infections.

Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8,16 and 32 μg/ml) as a photosensitizing agent and light emitting diode (635nm ± 10nm, 12 and 24 J/cm2), and evaluated the effects of photodynamic inactivation on five stains of Fusarium spp. and five strains of Exophiala spp, as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all stains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium stains with high MIC values of ≥16, 4-8, 4-8 and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after PDT treatment. Biofilms of both species showed high SMIC50 and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to AMB, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to PDT exhibited a distinct reduction in SMIC50 and SMIC80 compared to untreated groups for both species, except SMIC80 of ITC against Fusarium biofilms. In conclusion, in vitro photodynamic therapy was efficient in inactivation of Fusarium spp. and Exophiala spp., both planktonic cultures and biofilms. In addition, the combination of PDT and antifungal drugs represents an attractive alternative to the current antifungal strategies. However, further investigations are warranted for the reliable and safe application in clinical practice.

In vitro and in vivo interactions of minocycline and azoles, including itraconazole, voriconazole, and posaconazole, against filamentous pathogenic fungi were investigated. A total of 56 clinical isolates were studied in vitro via broth microdilution checkerboard technique, including 20 strains of Aspergillus fumigatus , 7 strains of Aspergillus flavus , 16 strains of Exophiala dermatitidis , 10 strains of Fusarium solani , and 3 strain s of Fusarium oxysporum .