Background: To develop an effective model of predicting fatal outcomes in the severe coronavirus disease 2019 (COVID-19) patients. Methods: Between February 20, 2020 and April 4, 2020, consecutive confirmed 2541 COVID-19 patients from three designated hospitals were enrolled in this study. All patients received chest computed tomography (CT) and serological examinations at admission. Laboratory tests included routine blood tests, liver function, renal function, coagulation profile, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and arterial blood gas. The SaO ₂ was measured using pulse oxygen saturation in room air at resting status. Independent high-risk factors associated with death were analyzed using Cox proportional hazard model. A prognostic nomogram was constructed to predict the survival of severe COVID-19 patients. Results: There were 124 severe patients in the training cohort, and there were 71 and 76 severe patients in the two independent validation cohorts, respectively. Multivariate Cox analysis indicated that age ≥ 70 years ( HR = 1.184, 95% CI 1.061–1.321), panting (breathing rate ≥ 30/min) ( HR = 3.300, 95% CI 2.509–6.286), lymphocyte count < 1.0 × 10 ⁹ /L ( HR = 2.283, 95% CI 1.779–3.267), and interleukin-6 (IL-6) > 10 pg/ml ( HR = 3.029, 95% CI 1.567–7.116) were independent high-risk factors associated with fatal outcome. We developed the nomogram for identifying survival of severe COVID-19 patients in the training cohort (AUC = 0.900, 95% CI 0.841–0.960, sensitivity 95.5%, specificity 77.5%); in validation cohort 1 (AUC = 0.811, 95% CI 0.763–0.961, sensitivity 77.3%, specificity 73.5%); in validation cohort 2 (AUC = 0.862, 95% CI 0.698–0.924, sensitivity 92.9%, specificity 64.5%). The calibration curve for probability of death indicated a good consistence between prediction by the nomogram and the actual observation. The prognosis of severe COVID-19 patients with high levels of IL-6 receiving tocilizumab were better than that of those patients without tocilizumab both in the training and validation cohorts, but without difference ( P = 0.105 for training cohort, P = 0.133 for validation cohort 1, and P = 0.210 for validation cohort 2). Conclusions: This nomogram could help clinicians to identify severe patients who have high risk of death, and to develop more appropriate treatment strategies to reduce the mortality of severe patients. Tocilizumab may improve the prognosis of severe COVID-19 patients with high levels of IL-6.

Herein, the effects of C-8 hydroxylation on the protective properties of dihydromyricetin (DHM) in a zebrafish larval model of diabetes and neurometabolic dysfunction were investigated. Diabetes was induced using alloxan and glucose, followed by treatment with DHM and its hydroxylated form, 8-hydroxy-dihydromyricetin (H-DHM), obtained through Beauveria bassiana fermentation. Biochemical, metabolomic, and transcriptomic analyses were conducted to evaluate their differences in efficacy. The results demonstrated that hydroxylation enhanced DHM's ability to improve locomotor activity, regulate Na⁺/K⁺-ATPase, Ca²⁺-ATPase, acetylcholinesterase, glutamate, and ATP levels, and modulate oxidative stress, as well as glucose and lipid homeostasis in diabetic zebrafish. Metabolomic analysis revealed that both DHM and H-DHM influenced key metabolic pathways, including amino acid metabolism, purine metabolism, and glycerophospholipid metabolism, while H-DHM specifically regulated sphingolipid metabolism. Transcriptomic analysis and weighted gene co-expression network analysis (WGCNA) further indicated that hydroxylation enhanced DHM's ability to target genes associated with pancreatic β-cell function, oxidative stress, and energy metabolism, such as DUSP26, ITLN1, gdf11, insl5a, pik3r5, gck, kcnj1a.6, tfr2, ebi3, KYAT3, and hdac12. The enhancement of DHM's regulatory effects on diabetes-associated neurometabolic dysfunction highlights the potential of fermentation-derived natural product derivatives for chronic disease management.