Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COV-ID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.

Highlights: COVID-19 has become a Public Health Emergency of International Concern (PHEIC) and a worldwide pandemic  The Lung Cleansing and Detoxifying Decoction has shown definite therapeutic effects on COVID-19 patients  Bioactive polysaccharides in the decoction appear to involve immunomodulatory activity, antiinflammatory activity, anti-oxidative activity and regulation of gut microbiota balance  Producing COVID-19 vaccines with polysaccharides as the adjuvants is an innovative strategy Abstract J o u r n a l P r e -p r o o f 2The new coronavirus pneumonia, named COVID-19 by the World Health Organization, has become a pandemic. It is highly pathogenic and reproduces quickly. There are currently no specific drugs to prevent the reproduction and spread of COVID-19. Some traditional Chinese medicines, especially the Lung Cleansing and Detoxifying Decoction (Qing Fei Pai Du Tang), have shown therapeutic effects on mild and ordinary COVID-19 patients. Polysaccharides are important ingredients in this decoction. This review summarizes the potential pharmacological activities of polysaccharides isolated by hot water extraction from Lung Cleansing and Detoxifying Decoction, which is consistent with its production method, to provide the theoretical basis for ongoing research on its application.

Background This study aims to identify a prognostic biomarker to predict the disease prognosis and reduce the mortality rate of COVID-19, which has caused a worldwide pandemic. Methods COVID-19 patients were randomly divided into training and test groups. Univariate and multivariate Cox regression analyses were performed to identify the disease prognosis signature, which was selected to establish a risk model in the training group. Furthermore, the disease prognosis signature of COVID-19 was validated in the test group. Results The signature of COVID-19 was combined with five indicators, namely neutrophil count, lymphocyte count, procalcitonin, older age, and C-reactive protein. The signature stratified patients into high- and low-risk groups with significantly relevant disease prognosis (log-rank test, P<0.001) in the training group. The survival analysis indicated that the high-risk group displayed substantially lower survival probability than the low-risk group (log-rank test P<0.001). The area under ROC curve (AUC) showed that the signature of COVID-19 displayed the highest predictive accuracy regarding disease prognosis, which was 0.955 in the training group and 0.945 in the test group. The ROC analysis of both groups demonstrated that the predictive ability of the signature surpassed the use of each of the five indicators alone. Conclusion The signature of COVID-19 presents a novel predictor and prognostic biomarker for closely monitoring patients and providing timely treatment for those who are severely or critically ill.

Submicron-sized poly(N-isopropyl acrylamide)/polyethyleneimine core-shell microgels were prepared in aqueous media by using tert-butyl hydroperoxide (TBHP) as an initiator, and then the gold nanoparticles (∼8 nm) were formed on the surface of the microgels. The amino groups on the polyethyleneimine (PEI) chains act as the binder for the assembly of the gold nanoparticles/microgel complex. In aqueous media the microgels are highly stable with the gold nanoparticles on their extended PEI chains, and this multi-scale nanoparticle complex can be recovered from water and redispersed in water. The nanogold/microgel particles were conjugated with the enzymes horseradish peroxidase (HRP) and urease. It is found that under identical assay conditions the enzyme/nanogold/microgel systems exhibit enhanced biocatalytic activity over free enzymes in solution, especially at lower enzyme concentrations. In addition, compared to free HRP, the HRP/nanogold/microgel systems show higher activity at varied pHs and temperatures, as well as higher storage stability. Thus the novel nanogold/microgel particles can serve as an excellent support for enzymes.

Even though multiple factors are involved in the high fluctuation of voriconazole (VCZ) plasma concentration, little is known regarding the influence of proinflammatory cytokines on VCZ concentration. The aim of this study was to investigate the influence of proinflammatory cytokines, namely, interleukin (IL)‐1β, IL‐6, IL‐18, interferon‐γ, tumor necrosis factor‐α, and transforming growth factor (TGF)‐β1 on VCZ trough concentration (VCZ‐Cmin) in Chinese patients with different forms of hematologic disorders. A total of 250 plasma samples from 113 patients were analyzed for VCZ‐Cmin and proinflammatory cytokines using a validated liquid chromatography–tandem mass spectrometry and enzyme‐linked immunosorbent assay methods, respectively. Patient demographics and clinical characteristics were obtained from hospital records. VCZ‐Cmin was significantly correlated with IL‐18 in acute myeloid leukemia (r = 0.456; P ˂ .0001), acute lymphoblastic leukemia (r = 0.317; P = .019), and chronic myeloid leukemia (r = 0.737; P = .004) while VCZ‐Cmin and TGF‐β1 were correlated (r = 0.436; P ˂ .001) in acute myeloid leukemia patients only. VCZ‐Cmin at different concentration range showed significant inhibitory effect of IL‐6. A backward multiple linear regression model revealed patient age (coefficient [β] = 0.025; P = .04), gamma‐glutamyl transferase (β = 0.003; P = .023), IL‐6 (β = –0.001; P = .024), proton pump inhibitor coadministration (β = 1.518; P = .002), and cytochrome P450 (CYP) 2C19 polymorphism as predictors of VCZ‐Cmin; however, these factors explained only 29% of VCZ‐Cmin variation. In conclusion, IL‐18 and TGF‐β1 have correlation with VCZ‐Cmin in Chinese patients with leukemia. Apparently, VCZ may have an inhibitory effect on IL‐6 levels. Furthermore, patient age, gamma‐glutamyl transferase, IL‐6, PPI coadministration, and cytochrome P450 2C19 polymormorphism partially predicted the VCZ‐Cmin. Therapeutic drug monitoring of VCZ in Chinese patients is highly encouraged.

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Objective: This study aimed to employ a population pharmacokinetic (PK) model to optimize the dosing regimen of voriconazole (VRC) in children with a critical illness. Methods: A total of 99 children aged from 0.44 to 13.58 years old were included in this study. The stability and predictive performance of the final model were evaluated by statistical and graphical methods. The optimal dosing regimen was proposed for children with different body weight, CYP2C19 phenotype, and co-administration with omeprazole. Results: The PK of VRC was described by a two-compartment model with nonlinear Michaelis-Menten elimination. Body weight, CYP2C19 phenotype, and omeprazole were significant covariates on maximum velocity of elimination (V max ), which had an estimated typical value of 18.13 mg·h −1 . Bayesian estimation suggested that dose-normalized concentration and total exposure (C max /D, C min /D, AUC 24 /D) were significantly different between extensive metabolizers (EM) patients and poor metabolizer (PM) patients. To achieve the target concentration early, two loading doses of 9 mg·kg −1 q12h were reliable for most children, whereas three loading doses of 6-7.5 mg·kg −1 q8h were warranted for young children weighted ≤18kg (except PM patients). The maintenance doses decreased about 30-40% in PM patients than that in EM patients. For children aged < 2 years in EM, the maintenance dose could be as high as 9 mg·kg −1 . The maintenance dose of VRC was supposed to decrease slightly when co-administration with omeprazole. Conclusion: A population PK model of intravenous VRC for critically ill children has been successful developed. It is necessary to adjust dosing regimens according to CYP2C19 genotype. The optimal dosing regimens have been recommended basing on the final model.

Aim Ferritin is a hepatic protein that plays vital roles in diagnosing and predicting diseases, but its potential in coronavirus disease 2019 (COVID-19) remains unknown. Method We collected clinical records from 79 COVID-19 patients at Wuhan Union hospital (China). Spearman’s correlation analysis, receiver operating characteristic (ROC) curve and Kaplan–Meier survival curves were employed. Results Patients with elevated ferritin levels had a higher incidence of severity illness (50.0 vs 2.9%) and liver injury (52.3 vs 20.0%) when compared with patients with normal ferritin levels ( p < 0.05). Ferritin could effectively identify the severity of illness (ROC area 0.873) and liver injury (ROC area 0.752). The elevated ferritin group showed longer viral clearance time (median 16 vs 6 days, p < 0.001) and in-hospital length (median 18 vs 10 days, p < 0.001). Conclusions It suggests that ferritin could act as an easy-to-use tool to identify liver injury and severity illness and predict the prognosis of COVID-19 patients. Intensive surveillance is necessary for patients with abnormal ferritin levels.